PUBLIC RELEASE DATE:

20-Nov-2014

Contact: Cristy Lytal lytal@med.usc.edu 323-442-2172 University of Southern California - Health Sciences

There are plenty of body parts that don't grow back when you lose them. Nails are an exception, and a new study published in the Proceedings of the National Academy of Sciences (PNAS) reveals some of the reasons why.

A team of USC Stem Cell researchers led by principal investigator Krzysztof Kobielak and co-first authors Yvonne Leung and Eve Kandyba has identified a new population of nail stem cells, which have the ability to either self-renew or undergo specialization or differentiation into multiple tissues.

To find these elusive stem cells, the team used a sophisticated system to attach fluorescent proteins and other visible "labels" to mouse nail cells. Many of these cells repeatedly divided, diluting the fluorescence and labels among their increasingly dim progeny. However, a few cells located in the soft tissue attached to the base of the nail retained strong fluorescence and labels because they either did not divide or divided slowly -- a known property of many stem cells.

The researchers then discovered that these slow-dividing stem cells have the flexibility to perform dual roles. Under normal circumstances, the stem cells contribute to the growth of both the nails and the adjacent skin. However, if the nail is injured or lost, a protein called "Bone Morphogenic Protein," or BMP, signals to the stem cells to shift their function exclusively to nail repair.

The researchers are now wondering whether or not the right signals or environmental cues could induce these nail stem cells to generate additional types of tissue -- potentially aiding in the repair of everything from nail and finger defects to severe skin injuries and amputations.

"That was very surprising discovery, since the dual characteristic of these nail stem cells to regenerate both the nail and skin under certain physiological conditions is quite unique and different from other skin stem cells, such as those of the hair follicle or sweat gland," said Kobielak.

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Nail stem cells prove more versatile than press ons

Researchers of CEU Cardenal Herrera University (CEU-UCH) for the first time transplanted bone marrow stem cells into damaged brain tissue while applying lipoic acid (a potent antioxidant), with the aim of improving neuroregeneration in the tissue. This new way of repairing brain damage, which combines cellular treatment with drug therapy, has shown positive results, especially in forming blood vessels (a process called angiogenesis) in damaged areas of the brains of adult laboratory mice. Angiogenesis is a process that is essential to the recovery of damaged neural tissues. The investigation was led by Jos Miguel Soria Lpez, deputy director of the Institute of Biomedical Sciences at CEU-UCH, and its results were published in the international medical journal Brain Injury.

Professor Soria, who is affiliated to the Department of Biomedical Sciences at CEU-UCH, heads the investigative group 'Strategies in Neuroprotection and Neuroreparation', which carried out the investigation in cooperation with the Andalusian Molecular Biology and Regenerative Medicine Centre (CABIMER), located in Sevilla, and the Mediterranean Ophthalmological Foundation, located in Valencia. The research team used the experience they obtained from their previous investigations on the neuroregenerative efficiency of lipoic acid to develop a new remediation strategy for patients of brain damage. This new therapy combines the transplantation of bone marrow stem cells into the brain -- in this case, the brains of adult rats -- with the administration of the potent antioxidant lipoic acid.

Lipoic acid is already used in the treatment of degenerative diseases such as multiple sclerosis or diabetic neuropathy. Professor Soria concluded from previous researches he conducted at CEU-UCH that it has the ability to increase the creation of blood vessels, which speeds up cerebral immune response after an injury and stimulates the restoration of damaged tissues. Several other researches, for their part, proved that after brain damage stem cell therapies using a patient's own bone marrow induce functional improvements. The two therapies -- one cellular; the other one pharmacological -- were both applied in this research so as to evaluate their combined effect.

New blood vessels

Angiogenesis -- the process that forms new blood vessels -- in the treated neuronal tissue began only eight days after the application of this new, combined therapy. CEU-UCH professor Soria says that "although bone marrow stem cells disappear from the brain tissue where they were transplanted after only 16 days, new cells keep forming. To put it another way, brain tissue is regenerated by new cells that appear in the brain as a result of stem cell transplantation. This proves the regenerative efficiency of the new combined therapy."

The research also shows how the blood vessels that formed after the treatment grow into the damaged area of the brain. "They act as a kind of scaffolding to that area that allows microglia cells to migrate," professor Soria says. "In the damaged area, they contribute to regeneration." He adds that "the application of both treatments results into high angiogenic activity, which is crucial for an efficient recovery of the damaged brain area." According to Soria, "the laboratory mice that recovered fastest from brain injuries were those that had a higher density of regenerated blood vessels."

Taking into consideration brain damage is, especially among children and adolescents, one of the leading causes of disability and death in the developed world, the good results that were obtained from the combination of the two therapies make the research team very hopeful. "Combining an antioxidant such as lipoic acid with bone marrow stem cells has proven to be an effective remedy," Soria observes. The team plans to conduct future research into similar combined therapies.

The image above shows the transplant of bone marrow stem cells from transgenic mice under the effects of cerebral cortex after suffering local brain damage. Also visible is a neuroprotective drug therapy.

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The above story is based on materials provided by Asociacin RUVID. Note: Materials may be edited for content and length.

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Brain injuries in mice treated using bone marrow stem cells, antioxidants

Katie Joyce, left, aged four, and Sophie Ryan Palmer, aged 12, were among the four children who died as a result of complications with transplants. Photograph: Steve Parsons/PA

Four children have died after failings in how stem cells used in life-saving operations were frozen at Great Ormond Street hospital, it emerged this week.

The four, who were between one and 12 years old, were among eight children with cancer whose bone marrow transplants did not work as a result of problems with the freezing process.

Britains best-known childrens hospital has admitted that one of them, four-year-old Katie Joyce, might have survived if it had acted more quickly when problems arose.

An inquest into the deaths this week heard that doctors were initially baffled as to why a decade of success using the procedures suddenly came to a halt in summer 2013. Despite extensive investigations, the hospital failed to pinpoint the source of the setbacks in its cryopreservation laboratory, used for freezing stem cells which were kept there for using in bone marrow transplants in children.

The transplanted stem cells were intended to help the childs bone marrow, damaged during chemotherapy, grow again to maximise the chance of recovery.

At the inquest, lawyers for two of the families whose children died accused Great Ormond Street of taking too long to halt the transplants once staff began having concerns.

The hospital has since overhauled its procedures to prevent further incidents and there are calls for the deaths to lead to tighter procedures around how stem cells are stored at hospitals and research centres across the UK.

Concerns were first raised in June 2013 when 12-year-old Sophie Ryan Palmer, who had acute lymphoblastic leukaemia, failed to make progress after her transplant at Great Ormond Street, which involved using a donors stem cells rather than her own.

By October 2013 the hospital had identified that a higher than usual proportion of eight patients who had undergone stem cell transplantation between March and August had suffered setbacks after encountering what doctors call delayed engraftment. It immediately stopped freezing stem cells on site at its base in Bloomsbury, central London, and launched an investigation.

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Great Ormond Street deaths caused by stem cell lab failures, inquest told