Dental pulp cell transplants help regenerate peripheral nerves

Fuente: http://medicalxpress.com/news/2015-07-dental-pulp-cell-transplants-regenerate.html

Peripheral nerve injuries often are caused by trauma or surgical complications and can result in considerable disabilities. Regeneration of peripheral nerves can be accomplished effectively using autologous (self-donated) nerve grafts, but that procedure may sacrifice a functional nerve and cause loss of sensation in another part of the patient's body.

Searching for an alternative to autologous nerve grafts (autografts), researchers in Japan transplanted mobilized dental pulp stem cells (MDPSCs) into laboratory rats with sciatic nerve defects to investigate the regenerative capabilities of MDPSCs and to compare the effectiveness of this procedure to what has been called the "gold standard,"- autologous nerve grafts or collagen implants, that were provided to control groups with similar nerve damage. For this study, the dental pulp used was derived easily from discarded teeth following extraction.

The researchers found that the group receiving the MDPSCs demonstrated regeneration of myelinated axons that were significantly higher in density than those resulting for controls that received nerve grafts or collagen.

Their study will be published in a future issue of Cell Transplantation and is currently freely available on-line as an unedited early e-pub.

"The total number of myelinated axons was greatest in the autograft group, followed by the MDPSC group and the collagen group," said study co-author Dr. Misako Nakashima, DDS, PhD, Department of Dental Regenerative Medicine, Center of Advanced Medicine for Dental and Oral Diseases, National Center for Geriatrics and Gerontology Research Institute in Obu, Japan. "The MDPSC group showed increased blood vessel formation, yet there was no statistical difference between the results found in the MDPSC group and the autograft group."

The researchers speculated that the MDPSCs may have had a stimulatory effect on residual Schwann cells (cells involved in many important aspects of peripheral nerve cell biology) through their secretion of neurotrophic factors. In in vitro experiments, the researchers found that MDPSCs had a beneficial effect on Schwann cells. That effect was amplified in in vivo studies.

The researchers concluded that "MDPSCs can contribute to peripheral nerve regeneration by the secretion of neurotrophic and angiogenic factors (factors that promote the formation of new blood vessels) when in close proximity to newly migrated Schwann cells" by regulating their apoptosis (programmed cell death) capability and proliferation.

"We predict that in the near future dental pulp stem cell transplantation may become a possible candidate for taking the place of autologous nerve grafts in peripheral nerve repair and regeneration," said the researchers.

"DPSCs are derived from the neural crest, making them attractive candidates for neural therapy and repair," said Dr. John R. Sladek, Jr., Professor of Neurology, Pediatrics, and Neuroscience, Department of Neurology at the University of Colorado School of Medicine and section editor for Cell Transplantation. "The avoidance of potential ethical issues often associated with the derivation of stem cells is also commendable. In this study, although MDPSCs exceeded autografts in axon density, the autografts had the highest total number of myelinated axons. Thus, comparative effectiveness studies should be conducted to compare cells with different lineages that have been proposed for nerve regeneration in order to determine which cell type yields optimal results. In addition, this study focused on the biological effects of MDPSC transplantation. Further studies should be conducted to ascertain the functional outcomes of this cell therapy for peripheral nerve regeneration."

More information: Yamamoto, T.; Osako, Y.; Ito, M.; Murakami, M.; Hayashi, Y.; Horibe, H.; Iohara, K.; Takeuchi, N.; Okui, N.; Hirata, H.; Nakayama, H.; Kurita, K.; Nakashima, M. Trophic Effects of Dental Pulp Stem Cells on Schwann Cells in Peripheral Nerve Regeneration. Cell Transplant. Appeared or available on-line: April 22, 2015. ingentaconnect.com/content/cog/ct/pre-prints/content-CT-1363_Yamamota_et_al

Journal reference: Cell Transplantation

Biologists reprogram skin cells to mimic rare disease

Fuente: http://www.eurekalert.org/pub_releases/2014-08/jhm-brs081914.php

Johns Hopkins stem cell biologists have found a way to reprogram a patient's skin cells into cells that mimic and display many biological features of a rare genetic disorder called familial dysautonomia. The process requires growing the skin cells in a bath of proteins and chemical additives while turning on a gene to produce neural crest cells, which give rise to several adult cell types. The researchers say their work substantially expedites the creation of neural crest cells from any patient with a neural crest-related disorder, a tool that lets physicians and scientists study each patient's disorder at the cellular level.

Previously, the same research team produced customized neural crest cells by first reprogramming patient skin cells into induced pluripotent stem (iPS) cells, which are similar to embryonic stem cells in their ability to become any of a broad array of cell types.

"Now we can circumvent the iPS cells step, saving seven to nine months of time and labor and producing neural crest cells that are more similar to the familial dysautonomia patients' cells," says Gabsang Lee, Ph.D., an assistant professor of neurology at the Institute for Cell Engineering and the study's senior author. A summary of the study will be published online in the journal Cell Stem Cell.

Neural crest cells appear early in human and other animal prenatal development, and they give rise to many important structures, including most of the nervous system (apart from the brain and spinal cord), the bones of the skull and jaws, and pigment-producing skin cells. Dysfunctional neural crest cells cause familial dysautonomia, which is incurable and can affect nerves' ability to regulate emotions, blood pressure and bowel movements. Less than 500 patients worldwide suffer from familial dysautonomia, but dysfunctional neural crest cells can cause other disorders, such as facial malformations and an inability to feel pain.

The challenge for scientists has been the fact that by the time a person is born, very few neural crest cells remain, making it hard to study how they cause the various disorders.

To make patient-specific neural crest cells, the team began with laboratory-grown skin cells that had been genetically modified to respond to the presence of the chemical doxycycline by glowing green and turning on the gene Sox10, which guides cells toward maturation as a neural crest cell.

Testing various combinations of molecular signals and watching for telltale green cells, the team found a regimen that turned 2 percent of the cells green. That combination involved turning on Sox10 while growing the cells on a layer of two different proteins and giving them three chemical additives to "rewind" their genetic memory and stimulate a protein network important for development.

Analyzing the green cells at the single cell level, the researchers found that they showed gene activity similar to that of other neural crest cells. Moreover, they discovered that 40 percent were "quad-potent," or able to become the four cell types typically derived from neural crest cells, while 35 percent were "tri-potent" and could become three of the four. The cells also migrated to the appropriate locations in chick embryos when implanted early in development.

The team then applied a modified version of the technique to skin cells from healthy adults and found that the skin cells became neural crests at a rate similar to the team's previous experiments.

Finally, the investigators used their regimen on skin cells from patients with familial dysautonomia, then compared these familial dysautonomia-neural crest cells to the control neural crest cells made from healthy adults. They identified 412 genes with lower activity levels in the familial dysautonomia-neural crest cells, of which 98 are involved in processing RNA products made from active genes.

According to the authors, this new observation offers insight into what goes wrong in familial dysautonomia.

"It seems as though the neural crest cells created directly from patient skin cells show more of the characteristics of familial dysautonomia than the neural crest cells we created previously from induced pluripotent stem cells," says Lee. "That means they should be better predictors of what happens in a particular familial dysautonomia patient, and whether or not a potential treatment will work for any given individual."

The method they devised should also be applicable to skin cells taken from people with any of the other diseases that result from dysfunctional neural crest cells, such as congenital pain disorders and Charcot-Marie-Tooth diseases, Lee says.

Link to article: http://dx.doi.org/10.1016/j.stem.2014.07.013

Adipose-derived stem cells and nerve regeneration

Fuente: http://www.sciencecodex.com/adiposederived_stem_cells_and_nerve_regeneration-139651

Stem cell researchers at the Blond McIndoe Laboratory, University of Manchester, UK, led by Dr Adam Reid, present a review of the current literature on the suitability of adipose-derived stem cells in peripheral nerve repair.

Injuries to peripheral nerves are common and cause life-changing problems for patients alongside high social and health care costs for society. Current clinical treatment relies on sacrificing a nerve from elsewhere in the body to provide a nerve graft at the injury site, but much work has been done to develop a bioengineered nerve graft that would not require this sacrifice. Stem cells are prime candidates as accelerators of regeneration in these nerve grafts.

This prospect, reported in Neural Regeneration Research (Vol. 9, No.14, 2014), presents the current literature on the potential of adipose-derived stem cells as tools to improve nerve regeneration through bioengineered nerve grafts. "Adipose-derived stem cells have the potential to stimulate improved nerve regeneration", stated the authors. "Their incorporation into bioengineered nerve graft treatments could revolutionize the current clinical approach to peripheral nerve repair".

Source: Neural Regeneration Research