Category Archives: California Stem Cells

Researchers found stem cells in mouse nails that performed two roles They cause nails to grow, and focus on repair when it is lost or injured The experts tracked how stem cells in the nails of mice split and grow It is hoped the same cells could be manipulated to grow tissue in other body parts

By Ellie Zolfagharifard for MailOnline

Published: 10:23 EST, 24 November 2014 | Updated: 10:23 EST, 24 November 2014

The blue-tailed skink has the remarkable ability to lose its tail to distract predators, and then grow a new one.

And someday, thanks to cells found in our nails, humans could have similar lizard-like abilities that will help us regrow lost limbs.

Researchers in the US recently found unique stem cells in nails that perform two roles - they cause nails to grow, and they focus on nail repair when it is lost or injured.

Researchers in the US recently found unique stem cells (shown in the above animation) in nails that perform two roles; they cause nails to grow, and focus on nail repair when it is lost or injured

The researchers claim these stem cells could be manipulated to grow tissue for other body parts, helping to someday recover lost limbs or organs.

The elusive stem cells were found at the University of Southern California by attaching dyes as 'labels' on mouse nail cells.

Many of these cells repeatedly divided, diluting the dyes and labels in the process.

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Could nails help us regrow LIMBS? Stem cells found on fingers and toes could someday give humans lizard-like abilities

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Newswise An antibody therapy already in clinical trials to treat chronic lymphocytic leukemia (CLL) may also prove effective against ovarian cancer and likely other cancers as well, report researchers at the University of California, San Diego School of Medicine in a study published in the Nov. 17 online early edition of the Proceedings of the National Academy of Sciences (PNAS).

The findings extend the anti-cancer potential of an experimental monoclonal antibody called cirmtuzumab, developed at UC San Diego Moores Cancer Center by Thomas Kipps, MD, PhD, and colleagues. Cirmtuzumab is currently in a first-in-human phase 1 clinical trial to assess its safety and efficacy in treating CLL.

Cirmtuzumab targets ROR1, a protein used by embryonic cells during early development and exploited by cancer cells to promote tumor growth and metastasis, the latter being responsible for 90 percent of all cancer-related deaths.

Because normal adult cells do not express ROR1, scientists suspect ROR1 is a specific biomarker of cancer cells in general and cancer stem cells in particular. Because it appears to drive tumor growth and disease spread, they believe it also presents an excellent target for anti-cancer therapies. Earlier research by Kipps and colleagues has shown a link between ROR1 and both breast cancer and CLL.

In their latest PNAS paper, Kipps and colleagues investigated whether cirmtuzumab also might be effective against ovarian cancer, which has rebuffed efforts to find a cure or long-term remedy. Most ovarian cancer patients initially respond well to standard chemotherapy, sometimes appearing to become disease-free, but 85 percent relapse within two years after systemic treatment, often with a more aggressive and disseminated form of the disease.

More than 21,000 women are diagnosed with ovarian cancer annually; more than 14,000 die from the disease each year. The 5-year survival rate after diagnosis is 44.6 percent.

The Moores Cancer Center team found that ovarian cancer stem cells, which are thought to be responsible for cancer recurrence and metastasis and are largely resistant to standard chemotherapies, singularly express ROR1. Patients whose tumors had high levels of ROR1 experienced more aggressive forms of ovarian cancer. They had higher rates of relapse and shorter median survival times than patients with lower levels of ROR1.

ROR1 is used by embryo cells to migrate and to develop new organs, said Kipps. Cancer stem cells subsequently use ROR1 for their own growth and dissemination throughout the body. They are essentially the seeds of the cancer. The more seeds a tumor has, the greater its ability to recur after therapy or metastasize.

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Anti-Leukemia Drug May Also Work Against Ovarian Cancer

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12-Nov-2014

Contact: Scott Maier scott.maier@ucsf.edu 415-502-6397 University of California - San Francisco @ucsf

A protein that may partly explain why human brains are larger than those of other animals has been identified by scientists from two stem-cell labs at UC San Francisco, in research published in the November 13, 2014 issue of Nature.

Key experiments by the UCSF researchers revealed that the protein, called PDGFD, is made in growing brains of humans, but not in mice, and appears necessary for normal proliferation of human brain stem cells growing in a lab dish.

The scientists made their discovery as part of research in which they identified genes that are activated to make specific proteins in crucial stem cells in the brain known as radial glial cells. The discovery stems from a collaboration between the laboratories of leading radial glial cell scientist Arnold Kriegstein MD, PhD, director of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF, and Michael Oldham, PhD, who recently made a rapid career leap from graduate student to principal investigator and Sandler Fellow at UCSF.

Radial glial cells make the neurons in the growing brain, including the neurons in the cerebral cortex, the seat of higher brain functions. The cerebral cortex varies in size 10,000-fold among mammals. Changes in the timing, location and degree of cell division and nerve cell generation by radial glial cells can dramatically alter the shape and function of the cortex.

The UCSF team discovered that PDGFD is secreted by human radial glial cells and acts on radial glial cells as well as other progenitor cells in the developing brain.

"To the best of our knowledge this is the first example of any signaling pathway affecting the proliferation of radial glial cells whose activity has changed during mammalian evolution," Oldham said. "We think that the expression of PDGFD in this signaling pathway is likely to be part of the reason the human brain is so much bigger that the mouse brain."

Although the UCSF research team found that the majority of genes that are active in radial glial cells are the same in humans and mice, they identified 18 genes that are active in human but not mouse radial glial cells during development of the cerebral cortex.

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Humans' big brains might be due in part to newly identified protein

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11-Nov-2014

Contact: Scott LaFee slafee@ucsd.edu 619-543-6163 University of California - San Diego @UCSanDiego

With the help of mouse models, induced pluripotent stem cells (iPSCs) and the "tooth fairy," researchers at the University of California, San Diego School of Medicine have implicated a new gene in idiopathic or non-syndromic autism. The gene is associated with Rett syndrome, a syndromic form of autism, suggesting that different types of autism spectrum disorder (ASD) may share similar molecular pathways.

The findings are published in the Nov. 11, 2014 online issue of Molecular Psychiatry.

"I see this research as an example of what can be done for cases of non-syndromic autism, which lack a definitive group of identifying symptoms or characteristics," said principal investigator Alysson Muotri, PhD, associate professor in the UC San Diego departments of Pediatrics and Cellular and Molecular Medicine. "One can take advantage of genomics to map all mutant genes in the patient and then use their own iPSCs to measure the impact of these mutations in relevant cell types. Moreover, the study of brain cells derived from these iPSCs can reveal potential therapeutic drugs tailored to the individual. It is the rise of personalized medicine for mental/neurological disorders."

But to effectively exploit iPSCs as a diagnostic tool, Muotri said researchers "need to compare neurons derived from hundreds or thousands of other autistic individuals." Enter the "Tooth Fairy Project," in which parents are encouraged TO register for a "Fairy Tooth Kit," which involves sending researchers like Muotri a discarded baby tooth from their autistic child. Scientists extract dental pulp cells from the tooth and differentiate them into iPSC-derived neurons for study.

"There is an interesting story behind every single tooth that arrives in the lab," said Muotri.

The latest findings, in fact, are the result of Muotri's first tooth fairy donor. He and colleagues identified a de novo or new disruption in one of the two copies of the TRPC6 gene in iPSC-derived neurons of a non-syndromic autistic child. They confirmed with mouse models that mutations in TRPC6 resulted in altered neuronal development, morphology and function. They also noted that the damaging effects of reduced TRPC6 could be rectified with a treatment of hyperforin, a TRPC6-specific agonist that acts by stimulating the functional TRPC6 in neurons, suggesting a potential drug therapy for some ASD patients.

The researchers also found that MeCP2 levels affect TRPC6 expression. Mutations in the gene MeCP2, which encodes for a protein vital to the normal function of nerve cells, cause Rett syndrome, revealing common pathways among ASD.

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Multiple models reveal new genetic links in autism

McLean Hospital and Harvard Stem Cell Institute scientists have new evidence that stem cell transplantation could be a worthwhile strategy to help epileptics who do not respond to anti-seizure drugs.

As reported in Cell Stem Cell, the laboratory of McLean Associate Neurobiologist Sangmi Chung, PhD, transplanted seizure-inhibiting, human embryonic stem cell-derived neurons into the brains of mice with a common form of epilepsy. Half of the mice who received the transplanted neurons no longer had seizures, while the other half experienced a significant drop in seizure frequency.

"After the transplantation we observed that the human neurons integrate into the epileptic brain," said Chung, who is also a Harvard Stem Cell Institute affiliated faculty member and an assistant professor at Harvard Medical School. "The transplanted neurons begin to receive excitatory input from host neurons and in turn generate inhibitory responses that reverse the electrical hyperactivity that cause seizures."

The recovery seen after the human stem cell-derived neuron transplants, which were done while the cells were still maturing into their full-grown form, is similar to that published in a 2013 study by University of California, San Francisco, scientists who transplanted fetal mouse brain cells into epileptic mice.

While encouraging, Chung noted that further primate studies and a process to purify the neurons, so only those known to inhibit seizures are transplanted (called interneurons), would need to be completed before a treatment in humans could be considered.

"Because embryonic stem cells can differentiate into many different cell types, even when we drive them into neurons, there are always other cell types," she said. "For clinical purposes, we need to make sure the cells are safe, without any contaminant. Currently we are working on a different method to specifically isolate interneurons."

Over 65 million people worldwide are affected by epileptic seizures, which can cause convulsions, loss of consciousness and other neurological symptoms. The exact cause of the condition is unknown, but it is hypothesized that diminished populations of interneurons is a contributor.

Most epileptic patients can be treated with anti-seizure drugs, which contain molecules that can inhibit electrical symptoms, similar to the normal function of interneurons. But about one-third do not benefit from existing medication. Patients may opt to have a portion of their brain cut out to control symptoms.

"This seems to be an area that needs a novel therapy," Chung said. "Before starting this project, I was a stem cell biologist mostly interested in the development of neural stem cells, but as I've come to know about epilepsy, I've become motivated to continue this research."

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Human stem cell-derived neuron transplants reduce seizures in mice

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Newswise Hematopoietic stem cells (HSCs) give rise to all blood and immune cells throughout the life of vertebrate organisms, from zebrafish to humans. But details of their genesis remain elusive, hindering efforts to develop induced pluripotent stem cell (iPSC) replacements that might address a host of blood disorders.

In a paper published Nov. 20 in the journal Cell, researchers at the University of California, San Diego School of Medicine describe the surprising and crucial involvement of a pro-inflammatory signaling protein in the creation of HSCs during embryonic development, a finding that could help scientists to finally reproduce HSCs for therapeutic use.

The recent breakthrough of induced pluripotency has made the concept of patient-specific regenerative medicine a reality, said principal investigator David Traver, PhD, professor in the Department of Cellular and Molecular Medicine. The development of some mature cell lineages from iPSCs, such as cardiac and neural, has been reasonably straightforward, but not with HSCs. This is likely due, at least in part, to not fully understanding all of the factors used by the embryo to generate HSCs. We believe the discovery that pro-inflammatory cues are important in vivo will help us recapitulate instruction of HSC fate in vitro from iPSCs.

Traver and colleagues specifically looked at the role of a cytokine (a type of cell signaling protein) called tumor necrosis factor alpha or TNFa, which plays a pivotal role in regulating systemic inflammation and immunity. The work extended previous research by Spanish biologist Victoriano Mulero, who had reported that TNFa was important in the function of the embryonic vascular system and that in animal models where TNF function was absent, blood defects resulted.

The Cell papers first author Raquel Espin-Palazon, a postdoctoral researcher in Travers lab and a former colleague of Muleros, determined that TNFa was required for the emergence of hematopoietic stem cells during embryogenesis in zebrafish a common animal model.

Traver said the finding was completely unexpected because HSCs emerge relatively early in embryonic formation when the developing organism is considered to be largely sterile and devoid of infection.

Thus, there was no expectation that pro-inflammatory signaling would be active at this time or in the blood-forming regions, Traver said. Equally surprising, we found that a population of embryonic myeloid cells, which are transient cells produced before HSCs arise, are the producers of the TNFa needed to establish HSC fate. So it turns out that a small subset of myeloid cells that persist for only a few days in development are necessary to help generate the lineal precursors of the entire adult blood-forming system.

The newly discovered role of TNFa in HSC development mirrors a parallel discovery regarding interferon gamma (INFg), another cytokine and major mediator of pro-inflammatory signaling, highlighting multiple inputs for inflammatory signaling in HSC emergence. Traver said the crucial roles of TNFa and INFg in HSC emergence are likely similar in humans because of the highly conserved nature of HSC development across vertebrate evolution.

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Before There Will Be Blood

11 hours ago In this multiple confocal analysis of transverse sections from transgenic zebrafish embryos, vasculature is labeled by red fluorescence, NF-kB protein complex that regulates inflammation by green fluorescence and nuclei by blue fluorescence. The arrowhead indicates a potential hematopoietic stem cell emerging in the dorsal aorta with high expression of NF-kB. The image at bottom right combines all channels. Credit: UC San Diego School of Medicine

Hematopoietic stem cells (HSCs) give rise to all blood and immune cells throughout the life of vertebrate organisms, from zebrafish to humans. But details of their genesis remain elusive, hindering efforts to develop induced pluripotent stem cell (iPSC) replacements that might address a host of blood disorders.

In a paper published Nov. 20 in the journal Cell, researchers at the University of California, San Diego School of Medicine describe the surprising and crucial involvement of a pro-inflammatory signaling protein in the creation of HSCs during embryonic development, a finding that could help scientists to finally reproduce HSCs for therapeutic use.

"The recent breakthrough of induced pluripotency has made the concept of patient-specific regenerative medicine a reality," said principal investigator David Traver, PhD, professor in the Department of Cellular and Molecular Medicine. "The development of some mature cell lineages from iPSCs, such as cardiac and neural, has been reasonably straightforward, but not with HSCs. This is likely due, at least in part, to not fully understanding all of the factors used by the embryo to generate HSCs. We believe the discovery that pro-inflammatory cues are important in vivo will help us recapitulate instruction of HSC fate in vitro from iPSCs."

Traver and colleagues specifically looked at the role of a cytokine (a type of cell signaling protein) called tumor necrosis factor alpha or TNF, which plays a pivotal role in regulating systemic inflammation and immunity. The work extended previous research by Spanish biologist Victoriano Mulero, who had reported that TNF was important in the function of the embryonic vascular system and that in animal models where TNF function was absent, blood defects resulted.

The Cell paper's first author Raquel Espin-Palazon, a postdoctoral researcher in Traver's lab and a former colleague of Mulero's, determined that TNF was required for the emergence of hematopoietic stem cells during embryogenesis in zebrafish a common animal model.

Traver said the finding was completely unexpected because HSCs emerge relatively early in embryonic formation when the developing organism is considered to be largely sterile and devoid of infection.

"Thus, there was no expectation that pro-inflammatory signaling would be active at this time or in the blood-forming regions," Traver said. "Equally surprising, we found that a population of embryonic myeloid cells, which are transient cells produced before HSCs arise, are the producers of the TNF needed to establish HSC fate. So it turns out that a small subset of myeloid cells that persist for only a few days in development are necessary to help generate the lineal precursors of the entire adult blood-forming system."

The newly discovered role of TNF in HSC development mirrors a parallel discovery regarding interferon gamma (INFg), another cytokine and major mediator of pro-inflammatory signaling, highlighting multiple inputs for inflammatory signaling in HSC emergence. Traver said the crucial roles of TNF and INFg in HSC emergence are likely similar in humans because of the highly conserved nature of HSC development across vertebrate evolution.

Explore further: New blood: Tracing the beginnings of hematopoietic stem cells

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Before there will be blood: Pro-inflammatory signaling plays surprising role in creation of hematopoietic stem cells

California-based biotech firm Organovo is set to begin selling 3-D-printed liver tissue by the end of the year, part of the growing movement to bring the technology to the medical field. Credit: Courtesy of Organovo

NEW YORK (CNNMoney) Add one more to the growing list of 3-D-printed products: human organs.

California-based biotech firm Organovo is set to begin selling 3-D-printed liver tissue by the end of the year, part of the growing movement to bring the technology to the medical field.

Organovo cant yet print a fully functioning liver. But the company has already been working with a handful of laboratories to manufacture live liver tissue, offering scientists a new way to conduct research.

This gives researchers the kind of tool that they just havent head in the past, said Michael Renard, executive vice president at Organovo. They cant do the kind of experiments on a person that they can do with this tissue in a lab setting.

Within the next few years, Renard says 3-D-printed tissues could also be used in patient treatment, to replace small parts or organs or encourage cell regeneration.

So how do you print human tissue?

The process starts when scientists grow human cells from biopsies or stem cells. They then feed the cells into special printers that can arrange them three-dimensionally by cell type in the way that theyd appear in the human body.

Once the cells have been printed in the right arrangement, they begin to signal to one another, fuse and organize themselves into a collective system.

Renard didnt want to speculate on when the printing of whole organs might become a reality, but many researchers are excited about the possibility and its implications for transplant procedures.

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Biotech company set to begin 3-D printing human tissue

California's nearly 10-year-old effort to develop therapies from stem cells is riding a technology wave that some folks are saying will pick up considerable momentum this year.

That is good news for the state's $3 billion stem cell agency, the California Institute of Regenerative Medicine, which will run out of cash for new grants in 2017 and which is looking for new sources of revenue from the private sector.

He said five clear themes emerged and one involved regenerative medicine. Temple, a former San Francisco Chronicle columnist, quoted James Canton, CEO of the Institute for Global Futures, as saying major strides are in the offing for 2014. In an email to Temple, Canton said,

Another one of Temple's futurists, David Houle, author of The Shift Age, said that sometime between now and 2020, 'our replacementparts will be superior to the parts we are born with.'

Whether the forecasts are correct or whether the IPO trend will continue is a bit beside the point for the stem cell agency. What they can profit from is the fact that this kind of news generates excitement among investors and among those who might be willing to make a major bet on the Golden State's stem cell agency. Fund-raising becomes easier when the public rhetoric is more than optimistic. The band wagon effect takes hold. The visions of hope that entranced 59 percent of California voters in 2004 when they created the stem cell agency seem much closer to reality.

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California Stem Cell Report: Growing Stem Cells and ...

Good news: A scientific breakthrough offers the hope of new treatments for diabetics such as Ryan Buhlman, of Warrnambool, who uses an insulin pump. Photo: Damian White

Harvard researchers have pioneered a technique to grow by the billions the insulin-producing cells diabetics lack, a breakthrough that might create new ways to treat the disease.

The breakthrough comes after 15 years of seeking a bulk recipe for making beta cells, which sense the level of sugar in the blood and keep it in a healthy range by making precise amounts of insulin, according to Harvard scientists led by Douglas Melton, who have published their work in the journal Cell. The process begins with human stem cells, which have the ability to become any type of tissue or organ.

The technique is an important step towards understanding and treating diabetes, a condition in which the pancreas's beta cells are insufficient or dead. Diabetes affects 347 million people worldwide, and its chronic high blood-sugar levels can injure hearts, eyes, kidneys, the nervous system and other tissues.

"This is part of the holy grail of regenerative medicine or tissue engineering, trying to make an unlimited source of cells or tissues or organs that you can use in a patient to correct a disease," said Albert Hwa, director of discovery science at JDRF, a New York-based diabetes advocacy group that funded Dr Melton's work.

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The procedure for making mature, insulin-secreting beta cells had taken years of painstaking research that led to a 30-day, six-step recipe, Dr Melton said. Laboratories would be able to use the cells to test drugs and learn more about how diabetes occurs, he said.

"They had to go through an awful lot of trial and error to get to this," said Jeanne Loring, director of the Scripps Research Institute's Centre for Regenerative Medicine in La Jolla, California. "The proof will be in how well this protocol works for people in other laboratories."

People with type 2 diabetes, in which the body loses its ability to produce insulin over time, usually take drugs that boost its production. About 15 per cent of patients with type 2 diabetes could not make enough of the hormone, even with drug treatment, and had tohave daily injections to replace it, Dr Melton said.

Type 1 diabetes destroys beta cells, and patients must carefully monitor their food and exercise while injecting appropriate doses of insulin to keep blood-sugar levels in a healthy range. While self-treatment technology had improved, nothing could replace human beta cells for controlling blood sugar, Dr Melton said.

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Diabetes researchers growing insulin-control cells by the billions