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Identification Of A Factor That Promotes Human Hematopoietic Stem Cell Self-Renewal

Technology Benefits

Increased efficiency and safety of HSC transplantationDoes not give self-renewing properties to non-self-renewing progenitor cellsMay provide better in vitro models for PSC-derived hematopoiesisImproved expansion capacity could enable “disease-in-a-dish” studies for hematological diseases using patient specific iPSC or other pluripotent stem cells

Technology Application

Maintain HSC self-renewalImprove the yield of transplantable HSCs during ex vivo expansionProlong the maintenance of an immunophenotypic HSPC population

Detailed Technology Description

The Mikkola group at UCLA has discovered a novel nuclear regulator of HSC differentiation that is expressed in human HSCs but not cultured human stem/progenitor cells (HSPCs). In vitro overexpression of the discovered factor improves both the expansion of cultured HSPCs and the engraftment of human HSPCs into immunodeficient mice. Moreover, overexpression of the nuclear factor did not confer self-renewal properties to non-self-renewing hematopoietic progenitors or prevent differentiation, suggesting that it does not reprogram progenitors to HSCs or leukemic stem cells but enhances self-renewal specifically in the context of undifferentiated HSPCs. Therefore, the overexpression of this regulator may be used to more efficiently expand human HSCs in vitro, and thereby improve the success of HSC transplantation.

Others

State Of Development

In vitro studies show that decreased expression of this nuclear factor causes a loss in the proliferative capacity of HSCs, while overexpression resulted in an enhancement of immunophenotypic HSPCs.
Mouse studies show that decreased expression of the novel self-renewal regulator impaired human HSC engraftment into immunodeficient mice, while overexpression improved engraftment.

Background

Given their multipotent capabilities, hematopoietic stem cells (HSCs) are routinely used in a number of cell-based and gene therapies to treat medical conditions, including hematologic diseases, immunodeficiencies, and genetic disorders. The success of such therapies is higher with an increased number of transplanted HSCs but the expansion of HSC cultures ex vivo remains a challenge. A method that increases the number of transplantable stem cells obtained during expansion could greatly improve the success of HSC-based cell and genetic therapies.

Tech ID/UC Case

27131/2016-990-0

Related Cases

2016-990-0

Country/Region

USA

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