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5 Days of Stem Cells
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Igor Slukvin

University of Wisconsin

Dr. Igor Slukvin is a Professor of Pathology and Laboratory Medicine and Cell and Regenerative Biology at the University of Wisconsin, Madison. He received his medical education and PhD degree at Kiev Medical University, Ukraine. After moving to the United States, he completed postdoctoral training and medical residency in pathology at UW Madison and later became the faculty member at the same institution. His research interest is in the understanding of cellular and molecular pathways leading to development of hematopoietic and vascular cells from human pluripotent stem cells (hPSCs). Dr. Slukvin also co-directs Precision Medicine Core at the Wisconsin National Primate Research Center which is focused on establishing next generation animal models and tools for the assessment precision stem cell therapies. His work is relevant for the development of novel sources of cells for bone marrow transplantation, transfusion and cancer and AIDS immunotherapies. He is a cofounder of Cellular Dynamics International and Cynata therapeutics biotechnology companies.


Advancing pluripotent stem cell technologies for research and therapy of blood diseases

Abstract


The derivation of human embryonic stem cells more than 20 years ago by James Thomson at University of Wisconsin followed by advances in cellular reprogramming have created alternative platforms for manufacturing blood cells for transfusion, immunotherapies and transplantation using human pluripotent stem cells (hPSCs). However, development of such therapies depends on our ability to produce the appropriate types of hematopoietic cells in sufficient quantities. Although we have demonstrated the feasibility of generating a variety of blood cell types from hPSCs, significant challenges remain, including de novo generation of hematopoietic stem cells (HSC) and robust production of lymphoid cells from hPSCs. This is due to the limited specification of adult-type definitive hematopoietic progenitors and predominance of myeloid-restricted embryonic hematopoiesis in hPSC differentiation cultures. In the embryo, lymphoid progenitors and hematopoietic stem cells (HSCs) arise from hemogenic endothelium (HE) lining arteries, but not veins. In our recent studies we identified HE in hPSC cultures and demonstrated the important role of NOTCH and arterial signaling in specification of definitive HE, thus providing an innovative strategy to aid in generating of definitive lymphomyeloid progenitors from hPSCs through enhancing arterial programming of HE. In addition, I will discuss our advances in direct blood programming technologies using modified mRNA and the utility of iPSC models for identifying novel factors involved in leukemia stem cell survival.