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Newswise Led by Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research member Dr. Hanna Mikkola, UCLA scientists have discovered a unique protein that is integral to the self-renewal of hematopoietic stem cells (HSCs) during human development.

This discovery lays the groundwork for researchers to generate HSCs in the lab (in vitro) that better mirror those that develop in their natural environment (in vivo). This could lead to improved therapies for blood-related diseases and cancers by enabling the creation of patient-specific blood stem cells for transplantation.

The findings are reported online November 13, 2014, ahead of print in the journal Cell Stem Cell.

The research community has long sought to harness the promise of pluripotent stem cells (PSCs) to overcome a significant roadblock in making cell-based therapies blood and immune diseases more broadly available, which has been hampered by the inability to generate and expand human HSCs in culture. HSCs are the blood forming cells that serve as the critical link between PSCs and fully differentiated cells of the blood system. The ability of HSCs to self-renew (replicate themselves) and differentiate to all blood cell types, is determined in part by the environment that the stem cell came from, called the niche.

In the five-year study, Mikkola and Drs. Sacha Prashad and Vincenzo Calvanese, members of Mikkolas lab and lead authors of the study, investigated a unique HSC surface protein called GPI-80. They found that it was produced by a specific subpopulation of human fetal hematopoietic cells that were the only group that could self-renew and differentiate into various blood cell types. They also found that this subpopulation of hematopoietic cells was the sole population able to permanently integrate into and thrive within the blood system of a recipient mouse.

Mikkola and colleagues further discovered that GPI-80 identifies HSCs during multiple phases of human HSC development and migration. These include the early first trimester of fetal development when newly generated HSCs can be found in the placenta, and the second trimester when HSCs are actively replicating in the fetal liver and the fetal bone marrow.

We found that whatever HSC niche we investigated, we could use GPI-80 as the best determinant to find the stem cell as it was being generated or colonized different hematopoietic tissues, said Mikkola, associate professor of molecular, cell and development biology at UCLA and also a member of the Jonsson Comprehensive Cancer Center. Moreover, loss of GPI-80 caused the stem cells to differentiate. This essentially tells us that GPI-80 must be present to make HSCs. We now have a very unique marker for investigating how human hematopoietic cells develop, migrate and function.

Mikkolas team is actively exploring different stages of human HSC development and PSC differentiation based on the GPI-80 marker, and comparing how blood stem cells are being generated in vitro and in vivo. This paves the way for scientists to redirect PSCs into patient-specific HSCs for transplantation into the patient without the need to find a suitable donor.

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UCLA Researchers Identify Unique Protein Key to the Development of Blood Stem Cells

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