Category Archives: Cell Medicine

Roy S. Herbst, MD, PhD, discusses the evolving treatment landscape of targeted therapies in nonsmall cell lung cancer.

Roy S. Herbst, MD, PhD, ensign professor of medicine (medical oncology), professor of pharmacology, Yale School of Medicine, director, the Center for Thoracic Cancers, chief, Medical Oncology, associate cancer center director, Translational Science, Yale Cancer Center, Smilow Cancer Hospital, discusses the evolving treatment landscape of targeted therapies in nonsmall cell lung cancer (NSCLC).

Multiple FDA approvals highlighted a busy year of action in the lung cancer space in 2021, Herbst says. The approval of osimertinib (Tagrisso) brought targeted therapy to the adjuvant setting for patients with stage I, II, and III NSCLC harboring EGFR mutations, Herbst explains. Moreover, the atezolizumab (Tecentriq) was approved for adjuvant treatment in patients with stage II to IIIA NSCLC whose tumors have PD-L1 expression on 1% or moreof tumor cells, Herbst adds.

These approvals have helped bring some of the best drugs and targeted therapies into earlier settings, Herbst continues. The approval of new targeted therapies, such as amivantamab-vmjw (Rybrevant) as the first treatment for adult patients with NSCLC harboring EGFR exon 20 insertion mutations, also demonstrate how the landscape has shifted, Hebst concludes.

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Dr. Herbst on the Evolution of Targeted Therapies in NSCLC - OncLive

By Digital Comms | April 4, 2022

Drs. Joanne Matsubara, Nika Shakiba, Ying Wang and Michael Kobor.

Four researchers in UBCs faculty of medicine are leading projects that received nearly $1 million from the Government of Canadas New Frontiers in Research Fund (NFRF).

They are amongst twelve UBC-led projects that were awarded over $2.8m through the NFRFs 2021 Exploration and Special Call Streams.

The Honourable Franois-Philippe Champagne, Minister of Innovation, Science and Industry, and the Honourable Jean-Yves Duclos, Minister of Health, announced a total of over $45 million in support for research projects through the NFRF. This combined investment is supporting 751 researchers, including 245 early career researchers. The projects were part of two competitions under the banner of the NFRF: the 2021 Exploration competition; and the NFRF special call on innovative approaches to research in the pandemic context.

Launched in 2018, the NFRF funds high risk-high reward, interdisciplinary, and transformative research led by Canadian researchers. The NFRF is designed to support world-leading innovation and enhance Canadas competitiveness and expertise in the global, knowledge-based economy.

The faculty of medicine researchers are:

Dr. Joanne MatsubaraProfessor, department of ophthalmology & visual sciencesProject: In Vivo Imaging for Investigating Neurodegenerative Diseases of the Brain and Eye Cell simulator: a computer-driven approach to genetically programming cells

$250,000 Exploration stream

Dr. Nika ShakibaAssistant professor, school of biomedical engineeringProject: Cell simulator: a computer-driven approach to genetically programming cells

$250,000 Exploration stream

Dr. Ying WangAssistant professor, department of pathology and laboratory medicineProject: Beyond morphology: Convert disease-related gene networks to pixels in digital pathology to solve the puzzle of vulnerable plaques that lead to cardiovascular events

$250,000 Exploration stream

Dr. Michael KoborProfessor, department of medical geneticsProject: Developing an integrated, innovative platform for retrospectively quantifying the prenatal and early child exposome using deciduous teeth

$237,708 Special call

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UBC Medicine researchers awarded nearly $1 million from New Frontiers in Research Fund - UBC Faculty of Medicine - UBC Faculty of Medicine

Stem Cell Investig. 2019; 6: 19.

1Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;

2Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran;

2Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran;

3Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

1Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;

2Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran;

3Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

Contributions: (I) Conception and design: E Fathi, R Farahzadi; (II) Administrative support: E Fathi, R Farahzadi; (III) Provision of study materials or patients: None; (IV) Collection and assembly of data: R Farahzadi, N Rajabzadeh; (V) Data analysis and interpretation: All authors; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

#These authors contributed equally to this work.

Received 2018 Nov 11; Accepted 2019 Mar 17.

Recent developments in the stem cell biology provided new hopes in treatment of diseases and disorders that yet cannot be treated. Stem cells have the potential to differentiate into various cell types in the body during age. These provide new cells for the body as it grows, and replace specialized cells that are damaged. Since mesenchymal stem cells (MSCs) can be easily harvested from the adipose tissue and can also be cultured and expanded in vitro they have become a good target for tissue regeneration. These cells have been widespread used for cell transplantation in animals and also for clinical trials in humans. The purpose of this review is to provide a summary of our current knowledge regarding the important and types of isolated stem cells from different sources of animal models such as horse, pig, goat, dog, rabbit, cat, rat, mice etc. In this regard, due to the widespread use and lot of attention of MSCs, in this review, we will elaborate on use of MSCs in veterinary medicine as well as in regenerative medicine. Based on the studies in this field, MSCs found wide application in treatment of diseases, such as heart failure, wound healing, tooth regeneration etc.

Keywords: Mesenchymal stem cells (MSCs), animal model, cell-based therapy, regenerative medicine

Stem cells are one of the main cells of the human body that have ability to grow more than 200 types of body cells (1). Stem cells, as non-specialized cells, can be transformed into highly specialized cells in the body (2). In the other words, Stem cells are undifferentiated cells with self-renewal potential, differentiation into several types of cells and excessive proliferation (3). In the past, it was believed that stem cells can only differentiate into mature cells of the same organ. Today, there are many evidences to show that stem cells can differentiate into the other types of cell as well as ectoderm, mesoderm and endoderm. The numbers of stem cells are different in the tissues such as bone marrow, liver, heart, kidney, and etc. (3,4). Over the past 20 years, much attention has been paid to stem cell biology. Therefore, there was a profound increase in the understanding of its characteristics and the therapeutic potential for its application (5). Today, the utilization of these cells in experimental research and cell therapy represents in such disorders including hematological, skin regeneration and heart disease in both human and veterinary medicine (6).The history of stem cells dates back to the 1960s, when Friedenstein and colleagues isolated, cultured and differentiated to osteogenic cell lineage of bone marrow-derived cells from guinea pigs (7). This project created a new perspective on stem cell research. In the following, other researchers discovered that the bone marrow contains fibroblast-like cells with congenic potential in vitro, which were capable of forming colonies (CFU-F) (8). For over 60 years, transplantation of hematopoietic stem cells (HSCs) has been the major curative therapy for several genetic and hematological disorders (9). Almost in 1963, Till and McCulloch described a single progenitor cell type in the bone marrow which expand clonally and give rise to all lineages of hematopoietic cells. This research represented the first characterization of the HSCs (10). Also, the identification of mouse embryonic stem cells (ESCs) in 1981 revolutionized the study of developmental biology, and mice are now used extensively as one of the best option to study stem cell biology in mammals (11). Nevertheless, their application a model, have limitations in the regenerative medicine. But this model, relatively inexpensive and can be easily manipulated genetically (12). Failure to obtain a satisfactory result in the selection of many mouse models, to recapitulate particular human disease phenotypes, has forced researchers to investigate other animal species to be more probably predictive of humans (13). For this purpose, to study the genetic diseases, the pig has been currently determined as one the best option of a large animal model (14).

Stem cells, based on their differentiation ability, are classified into different cell types, including totipotent, pluripotent, multipotent, or unipotent. Also, another classification of these cells are based on the evolutionary stages, including embryonic, fetal, infant or umbilical cord blood and adult stem cells (15). shows an overview of stem cells classifications based on differentiation potency.

An overview of the stem cell classification. Totipotency: after fertilization, embryonic stem cells (ESCs) maintain the ability to form all three germ layers as well as extra-embryonic tissues or placental cells and are termed as totipotent. Pluripotency: these more specialized cells of the blastocyst stage maintain the ability to self-renew and differentiate into the three germ layers and down many lineages but do not form extra-embryonic tissues or placental cells. Multipotency: adult or somatic stem cells are undifferentiated cells found in postnatal tissues. These specialized cells are considered to be multipotent; with very limited ability to self-renew and are committed to lineage species.

Toti-potent cells have the potential for development to any type of cell found in the organism. In the other hand, the capacity of these cells to develop into the three primary germ cell layers of the embryo and into extra-embryonic tissues such as the placenta is remarkable (15).

The pluripotent stem cells are kind of stem cells with the potential for development to approximately all cell types. These cells contain ESCs and cells that are isolated from the mesoderm, endoderm and ectoderm germ layers that are organized in the beginning period of ESC differentiation (15).

The multipotent stem cells have less proliferative potential than the previous two groups and have ability to produce a variety of cells which limited to a germinal layer [such as mesenchymal stem cells (MSCs)] or just a specific cell line (such as HSCs). Adult stem cells are also often in this group. In the word, these cells have the ability to differentiate into a closely related family of cells (15).

Despite the increasing interest in totipotent and pluripotent stem cells, unipotent stem cells have not received the most attention in research. A unipotent stem cell is a cell that can create cells with only one lineage differentiation. Muscle stem cells are one of the example of this type of cell (15). The word uni is derivative from the Latin word unus meaning one. In adult tissues in comparison with other types of stem cells, these cells have the lowest differentiation potential. The unipotent stem cells could create one cell type, in the other word, these cells do not have the self-renewal property. Furthermore, despite their limited differentiation potential, these cells are still candidates for treatment of various diseases (16).

ESCs are self-renewing cells that derived from the inner cell mass of a blastocyst and give rise to all cells during human development. It is mentioned that these cells, including human embryonic cells, could be used as suitable, promising source for cell transplantation and regenerative medicine because of their unique ability to give rise to all somatic cell lineages (17). In the other words, ESCs, pluripotent cells that can differentiate to form the specialized of the various cell types of the body (18). Also, ESCs capture the imagination because they are immortal and have an almost unlimited developmental potential. Due to the ethical limitation on embryo sampling and culture, these cells are used less in research (19).

HSCs are multipotent cells that give rise to blood cells through the process of hematopoiesis (20). These cells reside in the bone marrow and replenish all adult hematopoietic lineages throughout the lifetime of the human and animal (21). Also, these cells can replenish missing or damaged components of the hematopoietic and immunologic system and can withstand freezing for many years (22).The mammalian hematopoietic system containing more than ten different mature cell types that HSCs are one of the most important members of this. The ability to self-renew and multi-potency is another specific feature of these cells (23).

Adult stem cells, as undifferentiated cells, are found in numerous tissues of the body after embryonic development. These cells multiple by cell division to regenerate damaged tissues (24). Recent studies have been shown that adult stem cells may have the ability to differentiate into cell types from various germ layers. For example, bone marrow stem cells which is derived from mesoderm, can differentiate into cell lineage derived mesoderm and endoderm such as into lung, liver, GI tract, skin, etc. (25). Another example of adult stem cells is neural stem cells (NSCs), which is derived from ectoderm and can be differentiate into another lineage such as mesoderm and endoderm (26). Therapeutic potential of adult stem cells in cell therapy and regenerative medicine has been proven (27).

For the first time in the late 1990s, CSCs were identified by John Dick in acute myeloid diseases. CSCs are cancerous cells that found within tumors or hematological cancers. Also, these cells have the characteristics of normal stem cells and can also give rise to all cell types found in a particular cancer sample (28). There is an increasing evidence supporting the CSCs hypothesis. Normal stem cells in an adult living creature are responsible for the repair and regeneration of damaged as well as aged tissues (29). Many investigations have reported that the capability of a tumor to propagate and proliferate relies on a small cellular subpopulation characterized by stem-like properties, named CSCs (30).

Embryonic connective tissue contains so-called mesenchymes, from which with very close interactions of endoderm and ectoderm all other connective and hematopoietic tissues originate, Whereas, MSCs do not differentiate into hematopoietic cell (31). In 1924, Alexander A. Maxi mow used comprehensive histological detection to identify a singular type of precursor cell within mesenchyme that develops into various types of blood cells (32). In general, MSCs are type of cells with potential of multi-lineage differentiation and self-renewal, which exist in many different kinds of tissues and organs such as adipose tissue, bone marrow, skin, peripheral blood, fallopian tube, cord blood, liver and lung et al. (4,5). Today, stem cells are used for different applications. In addition to using these cells in human therapy such as cell transplantation, cell engraftment etc. The use of stem cells in veterinary medicine has also been considered. The purpose of this review is to provide a summary of our current knowledge regarding the important and types of isolated stem cells from different sources of animal models such as horse, pig, goat, dog, rabbit, cat, rat, mice etc. In this regard, due to the widespread use and lot of attention of MSCs, in this review, we will elaborate on use of MSCs in veterinary medicine.

The isolation method, maintenance and culture condition of MSCs differs from the different tissues, these methods as well as characterization of MSCs described as (36). MSCs could be isolated from the various tissues such as adipose tissue, bone marrow, umbilical cord, amniotic fluid etc. (37).

Diagram for adipose tissue-derived mesenchymal stem cell isolation (3).

Diagram for bone marrow-derived MSCs isolation (33). MSC, mesenchymal stem cell.

Diagram for umbilical cord-derived MSCs isolation (34). MSC, mesenchymal stem cell.

Diagram for isolation of amniotic fluid stem cells (AFSCs) (35).

Diagram for MSCs characterization (35). MSC, mesenchymal stem cell.

The diversity of stem cell or MSCs sources and a wide aspect of potential applications of these cells cause to challenge for selecting an appropriate cell type for cell therapy (38). Various diseases in animals have been treated by cell-based therapy. However, there are immunity concerns regarding cell therapy using stem cells. Improving animal models and selecting suitable methods for engraftment and transplantation could help address these subjects, facilitating eventual use of stem cells in the clinic. Therefore, for this purpose, in this section of this review, we provide an overview of the current as well as previous studies for future development of animal models to facilitate the utilization of stem cells in regenerative medicine (14). Significant progress has been made in stem cells-based regenerative medicine, which enables researchers to treat those diseases which cannot be cured by conventional medicines. The unlimited self-renewal and multi-lineage differentiation potential to other types of cells causes stem cells to be frontier in regenerative medicine (24). More researches in regenerative medicine have been focused on human cells including embryonic as well as adult stem cells or maybe somatic cells. Today there are versions of embryo-derived stem cells that have been reprogrammed from adult cells under the title of pluripotent cells (39). Stem cell therapy has been developed in the last decade. Nevertheless, obstacles including unwanted side effects due to the migration of transplanted cells as well as poor cell survival have remained unresolved. In order to overcome these problems, cell therapy has been introduced using biocompatible and biodegradable biomaterials to reduce cell loss and long-term in vitro retention of stem cells.

Currently in clinical trials, these biomaterials are widely used in drug and cell-delivery systems, regenerative medicine and tissue engineering in which to prevent the long-term survival of foreign substances in the body the release of cells are controlled (40).

Today, the incidence and prevalence of heart failure in human societies is a major and increasing problem that unfortunately has a poor prognosis. For decades, MSCs have been used for cardiovascular regenerative therapy as one of the potential therapeutic agents (41). Dhein et al. [2006] found that autologous bone marrow-derived mesenchymal stem cells (BMSCs) transplantation improves cardiac function in non-ischemic cardiomyopathy in a rabbit model. In one study, Davies et al. [2010] reported that transplantation of cord blood stem cells in ovine model of heart failure, enhanced the function of heart through improvement of right ventricular mass, both systolic and diastolic right heart function (42). In another study, Nagaya et al. [2005] found that MSCs dilated cardiomyopathy (DCM), possibly by inducing angiogenesis and preventing cardial fibrosis. MSCs have a tremendous beneficial effect in cell transplantation including in differentiating cardiomyocytes, vascular endothelial cells, and providing anti-apoptotic as well angiogenic mediators (43). Roura et al. [2015] shown that umbilical cord blood mesenchymal stem cells (UCBMSCs) are envisioned as attractive therapeutic candidates against human disorders progressing with vascular deficit (44). Ammar et al., [2015] compared BMSCs with adipose tissue-derived MSCs (ADSCs). It was demonstrated that both BMSCs and ADSCs were equally effective in mitigating doxorubicin-induced cardiac dysfunction through decreasing collagen deposition and promoting angiogenesis (45).

There are many advantages of small animal models usage in cardiovascular research compared with large animal models. Small model of animals has a short life span, which allow the researchers to follow the natural history of the disease at an accelerated pace. Some advantages and disadvantages are listed in (46).

Despite of the small animal model, large animal models are suitable models for studies of human diseases. Some advantages and disadvantages of using large animal models in a study protocol planning was elaborated in (47).

Chronic wound is one of the most common problem and causes significant distress to patients (48). Among the types of tissues that stem cells derived it, dental tissuederived MSCs provide good sources of cytokines and growth factors that promote wound healing. The results of previous studies showed that stem cells derived deciduous teeth of the horse might be a novel approach for wound care and might be applied in clinical treatment of non-healing wounds (49). However, the treatment with stem cells derived deciduous teeth needs more research to understand the underlying mechanisms of effective growth factors which contribute to the wound healing processes (50). This preliminary investigation suggests that deciduous teeth-derived stem cells have the potential to promote wound healing in rabbit excisional wound models (49). In the another study, Lin et al. [2013] worked on the mouse animal model and showed that ADSCs present a potentially viable matrix for full-thickness defect wound healing (51).

Many studies have been done on dental reconstruction with MSCs. In one study, Khorsand et al. [2013] reported that dental pulp-derived stem cells (DPSCs) could promote periodontal regeneration in canine model. Also, it was shown that canine DPSCs were successfully isolated and had the rapid proliferation and multi-lineage differentiation capacity (52). Other application of dental-derived stem cells is shown in .

Diagram for application of dental stem cell in dentistry/regenerative medicine (53).

As noted above, stem cells have different therapeutic applications and self-renewal capability. These cells can also differentiate into the different cell types. There is now a great hope that stem cells can be used to treat diseases such as Alzheimer, Parkinson and other serious diseases. In stem cell-based therapy, ESCs are essentially targeted to differentiate into functional neural cells. Today, a specific category of stem cells called induced pluripotent stem (iPS) cells are being used and tested to generate functional dopamine neurons for treating Parkinson's disease of a rat animal model. In addition, NSC as well as MSCs are being used in neurodegenerative disorder therapies for Alzheimers disease, Parkinsons disease, and stroke (54). Previous studies have shown that BMSCs could reduce brain amyloid deposition and accelerate the activation of microglia in an acutely induced Alzheimers disease in mouse animal model. Lee et al. [2009] reported that BMSCs can increase the number of activated microglia, which effective therapeutic vehicle to reduce A deposits in AD patients (55). In confirmation of previous study, Liu et al. [2015] showed that transplantation of BMSCs in brain of mouse model of Alzheimers disease cause to decrease in amyloid beta deposition, increase in brain-derived neurotrophic factor (BDNF) levels and improvements in social recognition (56). In addition of BMSCs, NSCs have been proposed as tools for treating neurodegeneration disease because of their capability to create an appropriate cell types which transplanted. kerud et al. [2001] demonstrated that NSCs efficiently express high level of glial cell line-derived neurotrophic factor (GDNF) in vivo, suggesting a use of these cells in the treatment of neurodegenerative disorders, including Parkinsons disease (57). In the following, Venkataramana et al. [2010] transplanted BMSCs into the sub lateral ventricular zones of seven Parkinsons disease patients and reported encouraging results (58).

The human body is fortified with specialized cells named MSCs, which has the ability to self-renew and differentiate into various cell types including, adipocyte, osteocyte, chondrocyte, neurons etc. In addition to mentioned properties, these cells can be easily isolated, safely transplanted to injured sites and have the immune regulatory properties. Numerous in vitro and in vivo studies in animal models have successfully demonstrated the potential of MSCs for various diseases; however, the clinical outcomes are not very encouraging. Based on the studies in the field of stem cells, MSCs find wide application in treatment of diseases, such as heart failure, wound healing, tooth regeneration and etc. In addition, these cells are particularly important in the treatment of the sub-branch neurodegenerative diseases like Alzheimer and Parkinson.

The authors wish to thank staff of the Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Funding: The project described was supported by Grant Number IR.TBZMED.REC.1396.1218 from the Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Conflicts of Interest: The authors have no conflicts of interest to declare.

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Stem cell-based regenerative medicine - PMC

In more than 140 labs across UCSF, scientists are carrying out studies in cell culture and animals with the goal of understanding and developing treatment strategies for such conditions as heart disease, diabetes, epilepsy, multiple sclerosis, Parkinsons disease, Lou Gehrigs disease, spinal cord injury and cancer.

The Broad Center is structured around eight research pipelines aimed at driving discoveries from the lab bench to the patient. Each pipeline focuses on a different organ system, including the blood, pancreas, liver, heart, reproductive organs, nervous system, musculoskeletal tissues, skin and eyes. Each of these pipelines is overseen by two leaders of international standing one representing the basic sciences and one representing clinical research. This approach has proven successful in the private sector for driving the development of new therapies.

Like all of UCSF, the Center fosters a highly collaborative culture, encouraging the cross-pollination of ideas between scientists of different disciplines and years of experience. Researchers studying pancreatic beta cells damaged in diabetes collaborate with those studying nervous system diseases, because at the heart of their research are stem cells that undergo similar molecular signaling on the way to becoming both cell types. The opportunity to work in this culture has drawn some of the countrys premier scientists to the center.

UCSF Mourns the Loss of EliBroad(1933-2021)

The UC San Francisco community is deeply saddened to learn of the passing of EliBroad, a renowned entrepreneur and philanthropist whose generosity supported scientific and medical research, the arts, and high-quality educational opportunities for students across the U.S.

The Eli and EdytheBroadCenter of Regeneration Medicine and Stem Cell Research at UCSF will be forever grateful to Mr.Broadfor his extraordinary vision and generosity. His investments in UCSFs stem cell endeavors have enabled our scientists to accelerate our research, by bringing some of the worlds leading stem cell scientists together under one roof and providing them with a setting that promotes collaboration and an exchange of ideas, both key to making clinical advances to improve human health. His legacy will live on through the breakthroughs and improvements in patient care made possible by his support of our work.

In fact, Mr.Broads impact on stem cell science at UCSF and beyond will be felt for generations to come. Along with his wife of over 60 years, Edye, Mr.Broadsupported stem cell research at a time when the country most needed national leadership in this area of scientific inquiry. Eager to leverage his philanthropic dollars for maximum impact, Mr.Broadsaw an opportunity to fund stem cell research when Californians passed a proposition funding $3 billion in bonds to support stem cell research and research facilities in 2004. Shortly after President George W. Bush vetoed a bill that would have supported federal funding of stem cell research, the couples philanthropic organization, The Eli and EdytheBroadFoundation, made an initial investment of $65 million to create three newBroadStem Cell Centers at UCSF, UCLA, and the University of Southern California. The Foundation has since made supplemental gifts bringing their total contribution to these centers to $113 million. The efforts have made California a leading center of stem cell research in the country.

To learn more about the remarkable life of EliBroad, please visitthis link.

In Memoriam: Katja Brueckner, PhD

In Memoriam: Zena Werb, MD, PhD

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Home | Eli and Edythe Broad Center of Regeneration ...

A patient living with HIV who received a blood stem cell transplant for high-risk acute myeloid leukemia has been free of the virus for 14 months after stopping HIV antiretroviral drug treatment, suggesting a cure, according to the Weill Cornell Medicine physician-scientists who performed the transplant and managed her care. As in two other successful cases that have been reported, the transplanted donor cells bore a mutation that makes them resistant to HIV infection.

The new case of long-term HIV remission was reported on Feb. 15 at the 29th annual Conference on Retroviruses and Opportunistic Infections, in Denver.

The patient received transplants of blood- and immune-cell replenishing stem cells after having her own blood cell population, including leukemic cells, destroyed by high-dose chemotherapy. The transplanted cells came from two sources: stem cells from a healthy adult relative were used to quickly restore her blood cell population to reduce infectious complications, and umbilical cord blood from an unrelated newborn child was used to provide long-term blood reconstitution.

Cord blood is used to supply blood stem cells for transplants for patients unable to find matched adult donors. Transplant specialists have found that cord blood may be used successfully even when they come from an unrelated donor whose immune markers only partially match the recipients.

Doctors in this case used cord blood containing an HIV-resistance gene variant called CCR532. HIV normally uses the CCR5 co-receptor to help it infect immune cells, but the receptors 32 variant effectively blocks viral entry.

Three months after the transplant, tests showed that the patients blood cell population was entirely derived from the HIV-resistant cord blood cells. Post-transplant studies could no longer detect HIV by various sensitive assays. The patient eventually stopped taking antiretroviral drugs to suppress her HIV infection, and so far, has been off the HIV drugs for 14 months, with no signs of HIV re-emergence after close follow-up during COVID 19 pandemicindicating a likely cure, although physicians at this stage prefer to call it long-term remission. She has also been leukemia-free for more than four years.

Two prior cases of long-term remission in HIV-positive cancer patients after adult CCR532 stem cell transplantation have been reported. This case is the first to use cord blood cells, and the first to treat a woman and someone who identifies as mixed-race. Since the CCR532 variant is much more common in people of European heritage, it is harder to find well-matched CCR532 donors for traditional stem cell transplants into nonwhite patients, although the use of cord blood partly alleviates this problem.

Stem cell transplant specialists Dr. Jingmei Hsu and Dr. Koen Van Besien and infectious disease specialist Dr. Marshall Glesby were the physician-scientists who led the NIH-funded clinical trial at Weill Cornell Medicine in collaboration with investigators at University of California Los Angeles, Johns Hopkins University School of Medicine and several other institutions.

The investigators concluded that cord blood containing the CCR532 variant offers a possible cure for both hematological malignancies and HIV and should be considered as a stem cell source when HIV-positive cancer patients need blood stem cell transplants. However, the procedure is considered too risky for HIV-positive patients who otherwise dont need such transplants.

Many Weill Cornell Medicine physicians and scientists maintain relationships and collaborations with external organizations to foster scientific innovation and provide expert guidance. Weill Cornell Medicine and its faculty make this information available to the public to ensure transparency. External relationship information is available on the faculty profiles of Dr. Jingmei Hsu, Dr. Koen Van Besien, and Dr. Marshall Glesby.

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Patient Possibly Cured of HIV Infection by Special Stem ...

Researchers led by Yevgeny Brudno, PhD, in the UNC-NCSU Joint Biomedical Engineering Department, have developed an implantable biotechnology that produces and releases CAR-T cells for attacking cancerous tumors.

Researchers from North Carolina State University and the University of North Carolina at Chapel Hill have developed an implantable biotechnology that produces and releases CAR-T cells for attacking cancerous tumors. In a proof-of-concept study involving lymphoma in mice, the researchers found that treatment with the implants was faster and more effective than conventional CAR-T cell cancer treatment.

T cells are part of the immune system, tasked with identifying and destroying cells in the body that have become infected with an invading pathogen. CAR-T cells are T cells that have been engineered to identify cancer cells and destroy them. CAR-T cells are already in clinical use for treating lymphomas, and there are many clinical trials under way focused on using CAR-T cell treatments against other forms of cancer.

A major drawback to CAR-T cell treatment is that it is tremendously expensive hundreds of thousands of dollars per dose, says Yevgeny Brudno, corresponding author of the study and assistant professor in the joint biomedical engineering department at NC State and UNC.

Due to its cost, many people are shut out from this treatment. One reason for the high cost is that the manufacturing process is complex, time-consuming and has to be tailored to each cancer patient individually, Brudno says. We wanted to address challenges in CAR-T treatment related to both manufacturing time and cost.

Reducing the manufacturing time is even more critical for patients with rapidly progressing disease, says Pritha Agarwalla, lead author of the study and a postdoctoral researcher in the joint biomedical engineering department.

To tackle this challenge, the researchers created a biotechnology called Multifunctional Alginate Scaffolds for T cell Engineering and Release (MASTER). The work was done in partnership with Gianpietro Dotti, professor in the Department of Microbiology and Immunology and co-leader of the Immunology Program at the Lineberger Cancer Center at UNC; and Frances Ligler, formerly the Ross Lampe Distinguished Professor of Biomedical Engineering at NC State and UNC and currently professor and Eppright Chair in Biomedical Engineering at Texas A&M.

To understand how MASTER works, you have to understand how CAR-T cells are produced. Clinicians first isolate T cells from patients and transport them to a clean manufacturing facility. At this facility, researchers activate T cells with antibodies over several days, preparing them for reprogramming. Once T cells are activated, researchers use viruses to introduce the CAR gene, reprogramming the T cells into CAR-T cells that target cancer cells. Researchers then add factors to stimulate the CAR-T cells to proliferate, expanding their number. Finally, after these manipulations are complete a process that can take weeks the cells are brought back to the hospital and infused into the patients bloodstream.

Our MASTER technology takes the cumbersome and time-consuming activation, reprogramming and expansion steps and performs them inside the patient, Agarwalla says. This transforms the multi-week process into a single-day procedure.

MASTER is a biocompatible, sponge-like material with the look and feel of a mini marshmallow. To begin treatment, researchers isolate T cells from the patient and mix these nave (or non-activated) T cells with the engineered virus. Researchers pour this mixture on top of the MASTER, which absorbs it. MASTER is decorated with the antibodies that activate the T cells, so the cell activation process begins almost immediately. Meanwhile, MASTER is surgically implanted into the patient in these studies, a mouse.

After implantation, the cellular activation process continues. As the T cells become activated, they begin responding to the modified viruses, which reprogram them into CAR-T cells.

The large pores and sponge-like nature of the MASTER material brings the virus and cells close together, which facilitates cellular genetic reprogramming, says Agarwalla.

The MASTER material is also impregnated with factors called interleukins that foster cell proliferation. After implantation, these interleukins begin to leach out, promoting rapid proliferation of the CAR-T cells.

Engineering the material so that it is dry and absorbs this combination of T cells and virus is critically important, Brudno says. If you try to do this by applying T cells and virus to a wet MASTER, it just doesnt work.

In these studies, the researchers worked with mice that had lymphoma. One group was treated with CAR-T cells that were created and delivered using MASTER. A second group was treated with CAR-T cells that were created conventionally and delivered intravenously. These two groups were compared to control group receiving non-engineered T cells.

Our technology performed very well, Brudno says. It would take at least two weeks to create CAR-T cells from nave T cells for clinical use. We were able to introduce the MASTER into a mouse within hours of isolating nave T cells.

In addition, since cells are implanted within hours of isolation, the minimal manipulation creates healthier cells that exhibit fewer markers associated with poor anti-cancer performance in CAR-T cells. Specifically, the MASTER technique results in cells that are less differentiated, which translates to better sustainability in the body and more anti-cancer potency. In addition, the cells display fewer markers of T-cell exhaustion, which is defined by poor T cell function.

The end result is that the mice that received CAR-T cell treatment via MASTER were far better at fighting off tumors than mice that received conventional CAR-T cell treatment, Agarwalla says.

The improvement in anti-cancer efficacy was especially pronounced over the long term, when mice were faced with a recurrence of lymphoma.

The MASTER technology was very promising in liquid tumors, such as lymphomas, but we are especially eager to see how MASTER performs against solid tumors including pancreatic cancer and brain tumors, Brudno says.

Were working with an industry partner to commercialize the technology, but theres still a lot of work to be done before it becomes clinically available. Further work to establish the safety and robustness of this technology in animal models will be necessary before we can begin exploring clinical trials involving human patients.

While its impossible to estimate what the cost of MASTER treatment might be if it is eventually approved for clinical use, Brudno says hes optimistic that it would be substantially less expensive than existing CAR-T treatment options.

Were also exploring opportunities with other industry partners for taking the fundamental concepts of MASTER and applying them for use in regenerative medicine and in treating autoimmune disease, Brudno says.

I feel like were just scratching the surface of whats possible here, Agarwalla says.

The paper, Bioinstructive Implantable Scaffolds for Rapid In Vivo Manufacture and Release of CAR-T Cells, is published in Nature Biotechnology. The paper was co-authored by Kristen Froehlich, a former undergraduate at NC State; Edikan Ogunnaike, Sarah Ahn of UNC; and Anton Jansson of NC State.

The work was done with support from the North Carolina Biotechnology Center, under flash grant 2019-FLG-3812; from the National Center for Advancing Translational Sciences; and from the National Institutes of Health under grants UL1TR002489, R01CA193140, R21-CA229938-01A1, T32CA196589 and R25NS094093.

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Implant Churns Out CAR-T Cells to Combat Cancer in Animal Models | Newsroom - UNC Health and UNC School of Medicine

INDIANAPOLIS, March 24, 2022 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) today announced that the U.S. Food and Drug Administration (FDA) has issued a complete response letter (CRL) for the Biologics License Application (BLA) for the investigational medicine sintilimab injection, a PD-1 inhibitor in combination with pemetrexed and platinum chemotherapy for the first-line treatment of people with nonsquamous non-small cell lung cancer (NSCLC). Sintilimab is being developed by Innovent Biologics, Inc. (HKEX: 01801) and Lilly.

The letter indicates that the review cycle is complete but the FDA is unable to approve the application in its current form, consistent with the outcome of the Oncologic Drugs Advisory Committee Meeting in February. The CRL includes a recommendation for an additional clinical study, specifically a multiregional clinical trial comparing standard of care therapy for first line metastatic NSCLC to sintilimab with chemotherapy utilizing a non-inferiority design with an overall survival endpoint.

Along with Innovent, Lilly is assessing next steps for the sintilimab program in the U.S.

About SintilimabSintilimab, is an investigational PD-1 inhibitor developed by Innovent and Lilly. Sintilimab is a type of immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1 / PD-Ligand 1 (PD-L1) pathway, and reactivates T-cells to kill cancer cells. Innovent is currently conducting more than 20 clinical studies of sintilimab to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registrational or pivotal clinical trials.

In China, sintilimab, marketed as TYVYT (sintilimab injection), has been approved for:

Additionally, Innovent currently has regulatory submissions under review in China for sintilimab:

Sintilimab was included in China's National Reimbursement Drug List (NRDL) for all four approved indications (listed above), according to the latest announcement from the China National Healthcare Security Administration ("NHSA").

About Eli Lilly and CompanyLilly is a global healthcare leader that unites caring with discovery to create medicines to make life better for people around the world. We were founded more than a century ago by a man committed to creating high-quality medicines that meet real needs, and today we remain true to that mission in all our work. Across the globe, Lilly employees work to discover and bring life-changing medicines to those who need them, improve the understanding and management of disease, and give back to communities through philanthropy and volunteerism. To learn more about Lilly, please visit http://www.lilly.com/and lilly.com/newsroom.

Lilly USA, LLC 2022. ALL RIGHTS RESERVED.

About Innovent Biologics' Strategic Collaboration with Eli Lilly and CompanyInnovent entered into a strategic collaboration with Lilly focused on biological medicine in March 2015 a groundbreaking partnership between a Chinese pharmaceutical company and a multinational pharmaceutical company. Under the agreement, Innovent and Lilly are co-developing and commercializing oncology medicines, including sintilimab in China. In October 2015, the two companies announced the extension of their existing collaboration to include co-development of three additional oncology antibodies targeting oncology indications. In August 2019, Innovent further entered a licensing agreement with Lilly to develop and commercialize a potentially global best-in-class diabetes medicine in China. Its collaboration with Lilly indicates that Innovent has established a comprehensive level of cooperation between China's innovative pharmaceuticals sector and the international pharmaceuticals sector in fields such as R&D, CMC, clinical development and commercialization. In August 2020Lilly and Innovent announced a global expansion of their strategic alliance for sintilimab, whereby Lilly obtained an exclusive license for sintilimab for geographies outside of China.

Note:TYVYT (sintilimab injection; Innovent) and BYVASDA (bevacizumab biosimilar injection; Innovent) are not approved products in the United States.

Eli Lilly and Company Forward-Looking StatementThis press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about sintilimab injection in combination with pemetrexed and platinum chemotherapy as a potential first-line treatment of people with nonsquamous non-small cell lung cancer and reflects Lilly's current beliefs and expectations. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of drug research, development, and commercialization. Among other things, there can be no guarantee that future study results will be consistent with study results to date, or that sintilimab will receive additional regulatory approvals or be commercially successful. For further discussion of these and other risks and uncertainties, see Lilly's most recent Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release.

Refer to:

Lauren Cohen; lcohen@loxooncology.com; (617) 678-2067 (media)

Kevin Hern; hern_kevin_r@lilly.com; (317) 277-1838 (investors)

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With obesity levels in the United States on the rise, researchers are studying what contributes to this condition at a molecular level.

Researchers from Ireland and Germany believe they have isolated specific cells that contribute to the inflammation associated with obesity. Their study, which appears in the journal Science Translational Medicine, addresses how managing certain cell components can help reduce obesity and the risk of related diseases such as type 2 diabetes.

According to 20172018 data from the Centers for Disease Control and Prevention (CDC), obesity affected 42.4% of adults in the U.S.

Health experts consider people overweight when their body mass index (BMI) reaches 25 and obese with a BMI of 30.

Several factors contribute to obesity, including food consumption and activity levels, but researchers are increasingly calling into question the so-called energy balance hypothesis of obesity. Trauma, stress, and some medications, such as steroids, can also contribute to weight gain.

Inflammation is a contributing factor to obesity. There are two types of inflammation: acute and chronic.

Acute inflammation occurs during an injury or infection. The immune system releases cytokines that aid in healing.

However, chronic inflammation is long lasting and can occur when a persons immune system is constantly overstimulated. When this occurs, certain functions in the body become dysregulated.

One major health issue relating to chronic inflammation is obesity.

Adipose tissue, or body fat, produces a type of cytokines. Health experts think an excessive amount of these proteins in people with obesity dysregulates the body, which could lead to metabolic disorders and heart disease.

Fat has traditionally been thought of as a passive storage organ for excess energy, but over the past couple of decades, it has been increasingly understood to have a huge number of other roles involved in metabolic signaling, Dr. Victoria Salem said in an interview with Medical News Today.

It has a rich blood and nerve supply and a complex interaction with the hormonal and immune systems.

Dr. Salem is a fellow in the Department of Bioengineering and an honorary consultant in Diabetes, Endocrinology, and General Internal Medicine at Victoria at Imperial College London.

The researchers speculated that the molecule PD-L1 plays a role in developing obesity. PD-L1 is a checkpoint protein involved in cell signaling within the immune system.

According to the authors, PD-L1 regulates adipose tissue immune cell composition.

Increasing evidence demonstrates profound dysregulation of the immune system in people with obesity [] leading to a state of low-grade inflammation, the authors write.

With this in mind, the researchers compared wild-type mice and mice genetically altered to lack PD-L1 in different types of cells, including dendritic, T cells, macrophages, and innate lymphoid cells. They fed both groups of mice a high fat diet and then compared which group had more weight gain.

They found that the mice lacking PD-L1 on their dendritic cells gained significantly more weight after 12 weeks on the high fat diet. This group also had increased insulin resistance, which leads to type 2 diabetes.

According to the authors, These results clearly demonstrate a critical role of the immunoregulator PD-L1 for the control of obesity.

This new process of checkpoint regulation of cells in visceral fat of obese individuals advances our understanding of how the immune system controls diet-induced weight gain that can lead to conditions such as obesity and type 2 diabetes, says study co-lead author Professor Padraic Fallon.

Prof. Fallon is the head of the Translational Immunology Group from Trinity College Dublins School of Medicine in Ireland.

After establishing the importance of PD-L1 in obesity with mice, the scientists accessed human studies and found that PD-L1 was up-regulated in people with obesity.

Only through our basic research efforts using preclinical models were we able to gain access to patients samples and link our findings to human disease, says co-lead author Dr. Christian Schwartz.

Dr. Schwartz is a principal investigator at University Hospital Erlangen in Germany.

The researchers hope that learning the importance of PD-L1 will factor into future weight loss treatments.

It will be interesting to investigate now how we can manipulate this checkpoint on specific cell populations of interest to help people with obesity, says Dr. Schwartz.

Dr. Mir Ali, a bariatric surgeon, spoke with MNT on the study findings.

This article is interesting in that another physiological pathway to obesity seems to be clarified, commented Dr. Ali. Since obesity is a complex interaction of hormonal and metabolic interactions, this sheds light on another mechanism.

In addition to being a surgeon, Dr. Ali is also medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, California.

Dr. Ali thinks the surgery could give hope to people with obesity in the future.

Potentially, there is a possibility of finding a safe and effective medication that may block this pathway to obesity, Dr. Ali said.

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Obesity and immune cells: What's the link? - Medical News Today

Bluebird bio has spent the better part of two decades developing gene therapies for rare diseases. This summer, after years of clinical trials, setbacks and delays, two of its experimental treatments could secure approval in the U.S.

Yet Bluebird is in a precarious position. The company warned investors this month that, with cash reserves dwindling rapidly, there is "substantial doubt" about its ability to remain solvent for the coming year.

Bluebird isn't the only cell and gene therapy developer facing a financial bind. Since December, at least nine other biotech companies working in the field have announced layoffs, cost cuts or restructured their research. Two others have sold off their manufacturing operations.

The retrenchment coincides with the sharpest market downturn for publicly traded drugmakers in years, which has forced tough choices on young startups and more established biotechs alike.

"We're seeing valuations for companies take a hit, down to the point that we're seeing multiple companies at negative enterprise value, which really is quite shocking to see," said Nessan Bermingham, a venture capitalist and former CEO of the gene editing biotech Intellia Therapeutics.

The stock market pain is shared by companies in other sectors of the biotech industry beyond cell and gene therapy, but developers of those types of medicines appear vulnerable.

Many aren't yet in the clinic and have yearslong research journeys ahead of them before it's clear whether their experimental treatments are likely to work. Developing and manufacturing gene therapies is also an expensive endeavor, stressing balance sheets at a moment when new investment is harder to come by.

Moreover, a string of clinical and regulatory stumbles has sapped investors' confidence in the ability of gene therapy companies to reliably turn cutting-edge science into approvable medicines.

"It's not a perfect storm, but it's a confluence of a lot of elements driving the issues we're seeing," said Bermingham, now an operating partner with Khosla Ventures.

For Amicus Therapeutics, a small biotech that for the past three years has built a pipeline of gene therapies, the market downturn hit at an inopportune time.

Last September, in somewhat better times for biotech stocks, Amicus announced plans to spin out its gene therapy business via a merger with a blank-check company. But by February, it was forced to call off the deal, citing "unfavorable market conditions" and an "increasingly challenging environment for stand-alone gene therapy companies."

As a result, Amicus said it would no longer advance multiple gene therapies into the clinic as intended and suspended plans to build a manufacturing plant. Thirty-five employees, or about 7% of the company, were laid off, most of whom had been involved in R&D.

Since December, Sigilon Therapeutics, Freeline Therapeutics, Gemini Therapeutics and Passage Bio have been forced to cut jobs as well. Meanwhile, Generation Bio, Avrobio, Sio Gene Therapies and Graphite Bio have reset their research, prioritizing certain experimental drugs or areas of research while stepping back from others.

"When you are in a position where you have to conserve capital, you are often going to prioritize indications where you believe have a higher probability of success as well as less competitive dynamics," said Luca Issi, an analyst at RBC Capital Markets. "We're going to see more of that."

The gene therapy contraction contrasts sharply with the past several years, during which new gene therapy companies won substantial funding and outlined expansive drug development plans. Since 2018, nearly 50 biotechs working on either cell or gene therapies priced an initial public offering. About half had yet to enter clinical testing at the time of their IPO Generation and Graphite among them.

While they weren't alone dozens of other biotechs outside of gene therapy did the same during the same period those companies are now more exposed as investors adjust their expectations for gene therapy.

"We saw a lot of companies go very early on," said Bermingham. "That's OK when markets are really strong," he added, but "becomes more challenging" in a downturn.

To Gbola Amusa, chief scientific officer at Chardan, the flood of preclinical companies launching IPOs in recent years has meant the average gene therapy biotech is less mature and therefore more susceptible to changing market conditions.

"A lot of the missteps and things we're hearing, sometimes it's because of [scientific challenges]," Amusa said. "The other times it's because of small companies that went public maybe too soon and are basically publicly traded academic enterprises without the capabilities that we would see with bigger biotechs."

As gene therapy companies have proliferated, so too has the number of experimental treatments entering clinical testing. According to the latest count by the Alliance for Regenerative Medicine, an industry group, there are more than 200 trials of gene therapies underway, with hundreds more in cell therapy.

One consequence of that progress is that more companies are running into problems in testing, whether due to newly uncovered safety risks or because of lower-than-expected efficacy.

Last year, Bluebird, UniQure and Allogene Therapeutics each halted studies after clinical trial participants developed cancer or, in the case of Allogene, signs of unusual DNA abnormalities. While all three companies were able to exonerate their treatments, the reports resurfaced concerns of whether gene therapy could heighten the risk of cancer.

The Food and Drug Administration has also appeared to be proceeding cautiously, even as it expects to approve more and more cell and gene therapies in the coming years. Last September, the agency convened a panel of experts to discuss one common type of gene therapy, a meeting that Bermingham said raised "orange flags" for companies in the field.

The FDA also issued more clinical holds, or regulatory suspensions, for cell and gene therapy trials in 2021 than in previous years. According to a Feb. 27 note from analysts at Jefferies, cell and gene therapy holds accounted for approximately 40% of those ordered by the regulator last year, despite representing well below that proportion of trials.

Beyond setting back individual companies, the trial halts might also be sparking broader questions about regulatory requirements and whether the field needs to do more work preclinically to assess certain risks.

On the other hand, clinical trial successes from more advanced cell and gene therapy developers could force companies earlier in testing to redraw their plans, particularly as many target some of the same rare diseases.

"I think you're going to see some of the business models and strategies be put under pressure by data that's come out from various groups," said Bermingham.

While more cell and gene therapy companies might restructure as stock prices remain depressed, clinical and regulatory progress from others could restore some of the field's attraction.

Beyond Bluebird's two treatments now up for approval, UniQure and BioMarin Pharmaceutical are expected to soon file for approval of gene therapies for hemophilia B and A, respectively. A sickle cell treatment from CRISPR Therapeutics and Vertex Pharmaceuticals is also nearing an FDA review.

Most large pharmaceutical companies are now invested in cell and gene therapy, too, buoying the partnership and acquisition activity that investors seek when backing new startups.

"Innovation takes time," said RBC's Issi. "We live in a bear market and gene therapy companies, many of them have limited cash. They are thinking creatively of how to continue to innovate."

Continued here:
As biotech retreats, gene therapy companies retrench and redraw plans - BioPharma Dive

A medical consultation that turned into an idea exchange chat and led to the launch of a company that, in a nutshell, is how Eyestem came into existence.

This cell therapy company was founded by a group of doctors and management consultants whose vision was to create a cell therapy platform to treat incurable diseases and make these technologies accessible to everyone.

Talking about its inception, co-founder and Chief Executive Officer Jogin Desai says, I met Rajani Battu, a senior ophthalmologist, in 2014 for a medical consultation. Both of us saw cell and gene therapy as the next frontier of medical innovation and the eye being the prime target for these therapies. We discussed that the approach taken by the western companies will result in therapies that will cost more than $400,000 per injection. We felt this was the right time to disrupt the field.

Cell and gene therapy is going to lead to a paradigm shift in healthcare. Diseases that were deemed incurable will start getting treatment because of this, say experts. Indian patients can benefit if a base is created here for these new platforms. Currently, such treatments are not sustainable due to the astronomical costs a therapy for spinal muscular atrophy can cost Rs 16 crore per patient. Eyestem intends to change that by keeping the cost low.

Big challengesEyestem treats incurable diseases by replacing the cells that are lost to conditions such as idiopathic pulmonary fibrosis, age-related macular degeneration and retinitis pigmentosa.

Age-related macular degeneration (AMD) is a leading cause of incurable blindness in the industrialised world. About 170 million people suffer from this disease; 40 million in India. It presents as two variants: wet and dry. Wet AMD is treatable and the global market value for this is about $8 billion.

Dry AMDs incidence is 9 times that of wet AMD and is incurable. Eyestems lab grown suspension of RPE cells helps in treating this condition. Retinitis pigmentosa (RP) is a group of rare, genetic disorders that affects children and causes complete vision loss by the age of 20. Some 5 million kids are estimated to suffer from this disease; 1.5 million in India. Eyecytes lab grown suspension of photoreceptor progenitor cells can be used to rescue the vision of these children. Idiopathic pulmonary fibrosis (IPF) is a serious chronic disease that makes breathing difficult and leads to cardiovascular complications. Once diagnosed, patients have a median survival period of 3-5 years. It is estimated that 5-6 million suffer from this globally. The companys lab grown suspension of cells can lead to improvement of the condition.

The company treats incurable diseases by replacing the cells that are lost to conditions such as idiopathic pulmonary fibrosis. (Pic: Team Eyestem)

A question of affordabilityThe company claims to be capital efficient and aims to get each product from concept to human trials in under $4 million. Most pharma companies spend 10 times this number to reach this stage, claims Desai.

On how soon the treatments can be commercialised, he says, Our treatment of dry AMD will go through first human trials by Q4 2022 and each new product to treat incurable diseases will be deployed 12 months after that. All of these are unmet needs and hence go through a fast-track clinical trial process. We expect to begin commercial availability of our flagship product by the end of 2024.

One of the experts in stem cells and regenerative medicine who is on the advisory board of the startup is Mahendra Rao, former Director of NIH Center for Regenerative Medicine (Washington, DC) and the CEO of Implant Therapeutics. He says he was impressed with the co-founders approach to work. They have ensured early engagement with DGCI and the FDA for their input and added experts to the board to ensure that their work meets international standards. They coordinated with LV Prasad Eye Hospital to help design a trial that is best suited for Indian patients."

Matter of fundingThe company says that it has been selective in raising funds as its purpose is not to raise money with higher valuations but to help patients. With its latest round of funding, it aims to upgrade its manufacturing process and deploy artificial intelligence to increase the predictability of its protocols. The company underscores they prefer to not talk about the money raised or valuation as their focus is not on such irrelevant metrics.

The angel round was led by myself and my team of senior ex-Quintiles executives from India, South Africa and Zurich. Endiya Partners and Kotak Private Equity joined in a subsequent pre-series A round. We are currently raising our series A and we are halfway there. 30% has been committed by current shareholders and we have soft commitment from a global venture fund for the other 20%. We anticipate closing this round in the next 8-12 weeks, adds Desai.

Nitin Deshmukh, senior advisor at Kotak Investment Advisors, says, Eyestem has taken a leadership position in developing allogeneic cell therapy products for ophthalmic conditions. We are happy with initial results seen in the product for treatment of age-related macular degeneration (AMD), a retinal degenerative disease.

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Eyestem has a visionary approach to make cell therapy affordable in India - Economic Times