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Protein key to harnessing regenerative power of blood stem cells identified by researchers

Date:
November 24, 2014
Source:
UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research
Summary:
A protein that is integral to the regulation of human blood stem cell regeneration has been uncovered by researchers. The study revealed that stem cells which lack the protein have markedly increased ability to replicate in vivo and following transplantation. The discovery provides new understanding of human stem cell self-renewal and paves the way for targeted therapies to make stem cells grow.
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In a study led by Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research member, Dr. John Chute, UCLA scientists have for the first time identified a unique protein that plays a key role in regulating blood stem cell replication in humans.

This discovery lays the groundwork for a better understanding of how this protein controls blood stem cell growth and regeneration, and could lead to the development of more effective therapies for a wide range of blood diseases and cancers.

The study was published online November 21, 2014 ahead of print in the Journal of Clinical Investigation.

Hematopoietic stem cells (HSCs) are the blood-forming cells that have the remarkable capacity to both self-renew and give rise to all of the differentiated cells (fully developed cells) of the blood system. HSC transplantation provides curative therapy for thousands of patients annually. However, little is known about the process through which transplanted HSCs replicate following their arrival in human bone marrow. In this study, the authors showed that a cell surface protein called protein tyrosine phosphatase-sigma (PTP-sigma) regulates the critical process called engraftment, meaning how HSCs start to grow and make health blood cells after transplantation.

Mamle Quarmyne, a graduate student the lab of Dr. Chute and first author of the study, demonstrated that PTP-sigma is produced (expressed) on a high percentage of mouse and human HSCs. She showed further that genetic deletion of PTP-sigma in mice markedly increased the ability of HSCs to engraft in transplanted mice.

In a complementary study, she demonstrated that selection of human blood HSCs which did not express PTP-sigma led to a 15-fold increase in HSC engraftment in transplanted immune-deficient mice. Taken together, these studies showed that PTP-sigma suppresses normal HSC engraftment capacity and targeted blockade of PTP-sigma can substantially improve mouse and human HSC engraftment after transplantation.

Chute and colleagues showed further that PTP-sigma regulates HSC function by suppressing a protein, RAC1, which is known to promote HSC engraftment after transplantation.

"These findings have tremendous therapeutic potential since we have identified a new receptor on HSCs, PTP-sigma, which can be specifically targeted as a means to potently increase the engraftment of transplanted HSCs in patients," said Chute, senior author of the study and UCLA Professor of Hematology/Oncology and Radiation Oncology. "This approach can also potentially accelerate hematologic recovery in cancer patients receiving chemotherapy and/or radiation, which also suppress the blood and immune systems."

Chute's team is now working with fellow UCLA researchers to test small molecules for their ability to specifically inhibit PTP-sigma on blood stem cells. If these studies are successful, they aim to translate these findings into clinical trials in the near future.


Story Source:

Materials provided by UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research. Note: Content may be edited for style and length.


Journal Reference:

  1. Mamle Quarmyne, Phuong L. Doan, Heather A. Himburg, Xiao Yan, Mai Nakamura, Liman Zhao, Nelson J. Chao, John P. Chute. Protein tyrosine phosphatase–σ regulates hematopoietic stem cell–repopulating capacity. Journal of Clinical Investigation, 2014; DOI: 10.1172/JCI77866

Cite This Page:

UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research. "Protein key to harnessing regenerative power of blood stem cells identified by researchers." ScienceDaily. ScienceDaily, 24 November 2014. <www.sciencedaily.com/releases/2014/11/141124143414.htm>.
UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research. (2014, November 24). Protein key to harnessing regenerative power of blood stem cells identified by researchers. ScienceDaily. Retrieved March 27, 2024 from www.sciencedaily.com/releases/2014/11/141124143414.htm
UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research. "Protein key to harnessing regenerative power of blood stem cells identified by researchers." ScienceDaily. www.sciencedaily.com/releases/2014/11/141124143414.htm (accessed March 27, 2024).

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