Navigation Links
Scientists create 'endless supply' of myelin-forming cells
Date:11/1/2012

In a new study appearing this month in the Journal of Neuroscience, researchers have unlocked the complex cellular mechanics that instruct specific brain cells to continue to divide. This discovery overcomes a significant technical hurdle to potential human stem cell therapies; ensuring that an abundant supply of cells is available to study and ultimately treat people with diseases.

"One of the major factors that will determine the viability of stem cell therapies is access to a safe and reliable supply of cells," said University of Rochester Medical Center (URMC) neurologist Steve Goldman, M.D., Ph.D., lead author of the study. "This study demonstrates that in the case of certain populations of brain cells we now understand the cell biology and the mechanisms necessary to control cell division and generate an almost endless supply of cells."

The study focuses on cells called glial progenitor cells (GPCs) that are found in the white matter of the human brain. These stem cells give rise to two cells found in the central nervous system: oligodendrocytes, which produce myelin, the fatty tissue that insulates the connections between cells; and astrocytes, cells that are critical to the health and signaling function of oligodendrocytes as well as neurons.

Damage to myelin lies at the root of a long list of diseases, such as multiple sclerosis, cerebral palsy, and a family of deadly childhood diseases called pediatric leukodystrophies. The scientific community believes that regenerative medicine in the form of cell transplantation holds great promise for treating myelin disorders. Goldman and his colleagues, for example, have demonstrated in numerous animal model studies that transplanted GPCs can proliferate in the brain and repair damaged myelin.

However, one of the barriers to moving forward with human treatments for myelin disease has been the difficulty of creating a plentiful supply of necessary cells, in this case GPCs. Scientists have been successful at getting these cells to divide and multiply in the lab, but only for limited periods of time, resulting in the generation of limited numbers of usable cells.

"After a period of time, the cells stop dividing or, more typically, begin to specialize and form astrocytes which are not useful for myelin repair," said Goldman. "These cells could go either way but they essentially choose the wrong direction."

Overcoming this problem required that Goldman's lab master the precise chemical symphony that occurs within stem cells, and which instructs them when to divide and multiply, and when to stop this process and become oligodendrocytes and astrocytes.

One of the key players in cell division is a protein called beta-catenin. Beta-catenin is regulated by another protein in the cell called glycogen synthase kinase 3 beta (GSK3B). GSK3B is responsible for altering beta-catenin by adding an additional phosphate molecule to its structure, essentially giving it a barcode that the cell then uses to sort the protein and send it off to be destroyed. During development, when cell division is necessary, this process is interrupted by another signal that blocks GSK3B. When this occurs, the beta-catenin protein is spared destruction and eventually makes its way to the cell's nucleus where it starts a chemical chain reaction that ultimately instructs the cell to divide. However, after a period of time this process slows and, instead of replicating, the cells begin to then commit to becoming one type or another. The challenge for scientists was to find another way to essentially trick these cells into continuing to divide, and to do so without risking the uncontrolled growth that could otherwise result in tumor formation.

The new discovery hinges on a receptor called protein tyrosine phosphatase beta/zeta (PTPRZ1). Goldman and his team long suspected that PTPRZ1 played an important role in cell division; the receptor shows up prominently in molecular profiles of GPCs. After a six-year effort to discern the receptor's function, they found that it works in concert with GSK3B and helps "label" beta-catenin protein for either destruction or nuclear activity. The breakthrough was the identification of a molecule called pleiotrophin that essentially blocks the function of the PTPRZ1 receptor. They found that by regulating the levels of pleiotrophin, they were able to essentially "short circuit" PTPRZ1's normal influence on cell division, allowing the cells to continue dividing.

While the experiments were performed on cells derived from human brain tissue, the authors contend that the same process could also be applied to GPCs derived from embryos or from "reprogrammed" skin cells. This would greatly expand the number of cells potentially derived from single patient samples, whether for transplantation back to those same individuals or for use in other patients.


'/>"/>

Contact: Mark Michaud
mark_michaud@urmc.rochester.edu
585-273-4790
University of Rochester Medical Center
Source:Eurekalert

Related medicine news :

1. Scientists solving the mystery of human consciousness
2. Scientists uncover multiple faces of deadly breast cancer
3. Scientists identify major source of cells defense against oxidative stress
4. Scientists tailor cell surface targeting system to hit organelle ZIP codes
5. Scientists rewrite rulebook on breast cancer in landmark global study
6. Warwick scientists uncover how checkpoint proteins bind chromosomes
7. NIH scientists link quickly spreading gene to Asian MRSA epidemic
8. Joslin scientists identify important mechanism that affects the aging process
9. Scripps Research scientists show how memory B cells stay in class to fight different infections
10. Scientists Map Melanomas Genome
11. A*STAR scientists discover switch to boost anti-viral response to fight infectious diseases
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/21/2017)... ... ... As recently as 2015, rhinoplasty was one of the Top 5 cosmetic ... patients want to make a change in the appearance of their nose while others ... team at usrhinoplasty.org is expanding its article database to better inform its ...
(Date:2/21/2017)... ... 2017 , ... American Veterinarian™, the premier multimedia provider of ... first bi-monthly issue of 2017 in February. The inaugural issue will offer expert ... , In making the announcement, American Veterinarian™ Publisher Chris Hennessy said, “We ...
(Date:2/21/2017)... San Francisco, California (PRWEB) , ... February 21, ... ... in the world with over 50,000 participants. The connected care demonstration spanned ... Office of the National Coordinator, roughly 30% of providers have no Health Information ...
(Date:2/21/2017)... ... February 21, 2017 , ... Along with Valentine’s Day, February marks ... small changes that can lead to a lifetime of heart health. In addition, ... emergency. , The Athletic Trainers’ Society of New Jersey (ATSNJ) is urging ...
(Date:2/20/2017)... ... 20, 2017 , ... Daily Body Restore, "DBR" a company ... “good” bacteria in the body, announced its Daily Body Restore® supplement is now ... Body Restore® is made with a unique combination of digestive enzymes and probiotics ...
Breaking Medicine News(10 mins):
(Date:2/21/2017)... 21, 2017 Mass Spectrometer Market: Overview ... This report on mass spectrometer ... prospects of the market globally. The stakeholders of ... the manufacture and commercialization of various mass spectrometer ... planning to enter this market. This report comprises ...
(Date:2/21/2017)... -- Luminex Corporation (NASDAQ: LMNX ) (the "Company") today ... of a quarterly cash dividend to its shareholders, the first ... payable on April 14, 2017 to shareholders of record as ... The board of directors intends for the Company ... holders of its common stock, representing a planned annual dividend ...
(Date:2/21/2017)... Feb. 21, 2017  Global health services company Cigna ... ® for breast reconstruction surgery and Dermacell ... an advanced acellular dermal matrix developed by LifeNet Health ... NVDQ ) "We are proud ... health-care payers to review the growing base of evidentiary ...
Breaking Medicine Technology: