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Engineering long term multipotent hematopoietic cells from human pluripotent stem cells
7th Annual Conference on Stem Cell and Regenerative Medicine
August 04-05, 2016 Manchester, UK
Ryohichi Sugimura
Harvard Medical School/Boston Children�??s Hospital, USA
Posters & Accepted Abstracts: J Stem Cell Res Ther
Abstract:
Hematopoietic stem cell (HSC) transplantation is an important curative source for malignant and non malignant blood diseases. However, HSC transplantation has limitations, including donor availability and immunologic mismatch. To resolve these issues, researchers have been mounting considerable efforts to induce HSCs from autologous sources such as induced pluripotent stem cells, hematopoietic precursors and fibroblasts. Human pluripotent stem cells (hPSCs) are intriguing platform that allow for large scale expansion culture and correction of mutations. Achieving the formation of HSCs from hPSCs would transform our ability to model and treat hematologic disease from autologous stem cells. Desired cell types have been generated from hPSCs by two approaches, one is biomimetics of developing embryos in 3D culture by supplementing signaling factors; the other is synthetic biology by exogenously expressing transcription factors (TFs). Either approach has not achieved fully functional HSCs from hPSCs so far. Thus combination of these two, biomimetic 3D culture to derive hematopoietic precursors followed by exogenous expression of TFs was taken in this study. The hPSCs was differentiated to precursors of hematopoietic cells in 3D culture; those precursors, still lacking robust hematopoietic capacity (e.g., engraftment upon transplantation) in vivo was induced expression of TFs specific to HSCs. Upon transplantation to immune deficient mouse models, long term and multi lineage reconstitution was observed. The future direction of this work is gene correction of hPSC derived hematopoietic cells, for example, Cas9 mediated genome editing of congenital anemia. This work will provide a significant platform to produce human HSCs for potential clinical applications as well as better understanding of hematopoiesis.