Generation of Engraftable Hematopoietic Stem Cells from Induced Pluripotent Stem Cells


Engraftment Challenge in Bone Marrow Transplantation
Bone marrow transplant is currently used to treat leukemia, lymphoma and genetic bone marrow failure disorders, but it can be highly risky especially when a closely matched donor is not available. Only one third of patients even have a viable donor for bone marrow transplantation. Generation of autologous hematopoietic stem cells (HSCs) engraftable in the bone marrow would improve safety and provide a source of cells for all HSC transplants without the need for donor matches. The challenge has been that iPS-derived HSCs do not engraft in the bone marrow when injected into immune deficient mice. Recently a study by Sugimura et al. (Nature, 2017) identified seven transcription factors (ERG, HOXA5, HOXA9, HOXA10, LCOR, RUNX1 and SPI1) that, when over-expressed in an iPS cell result in an engraftable HSC. However, over-expression of these seven genes by lentiviral transduction is not an ideal solution for several reasons including its cost, feasibility at commercial scale, and potential risk of harm from multiple over-expressed transcription factors.

Small Molecule Treatment on iPSC
A University of Colorado research group led by Dr. Michael Verneris has developed a novel process to create autologous HSCs that are engraftable in patient bone marrow. Human iPS cells are treated with a small molecule (SM1). SM1 changes the gene expression in iPS-derived HSCs, giving them a genetic signature associated with bone marrow engraftment in mice and the associated ability to engraft in mice.
In addition, treatment with SM1 resulted in more than two-fold expansion of HSCs over the course of 12 days of culture (figure 1), and led to increased iPSC-derived human HSC engraftment in immune-deficient mice (figure 2).


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For Information, Contact:
Doreen Molk
University of Colorado
Michael Verneris
Seonhui Shim
Disease Areas:
Regenerative Medicine
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