Ryohichi (Rio) Sugimura
Harvard Medical School, USA
Title: Engineering long-term multipotent hematopoietic cells from human pluripotent stem cells
Biography
Biography: Ryohichi (Rio) Sugimura
Abstract
Hematopoietic stem cell (HSC) transplantation is an important curative source for malignant and nonmalignant 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. 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, were 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.