IRCMS International Research Center for Medical Sciences

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IRCMS Seminars

[September 12] 55th IRCMS Seminar

August 28 2019

We would like to inform you that the 55th IRCMS Seminar has been scheduled as below. We would be pleased to see many of you participating in the seminar.

Date       : September 12, 2019 (Thursday)
Time     : 16:00-17:00
Venue    : IRCMS 1F Meeting Lounge 
Speaker : Adam C Wilkinson, Ph.D.
                Postdoctoral Research Fellow
                Stanford Institute for Stem Cell Biology and Regenerative Medicine,
                Stanford University, USA

Tilte       : Long-Term Ex Vivo Expansion Of Hematopoietic Stem Cells

Abstract:

The self-renewal of multipotent hematopoietic stem cells (HSCs) is key for life-long maintenance of hematopoiesis and the curative capacity of clinical bone marrow transplantation. However, while in vivo HSC self-renewal capacity has been well-described, existing culture conditions poorly support ex vivo HSC self-renewal and afford a very limited window to study or modify HSCs in-a-dish. By taking a reductionist optimization approach, we have developed a simple culture platform that supports functional mouse HSCs ex vivo over 1-2 months. Importantly, we identified the synthetic polymer polyvinyl alcohol as a superior, inexpensive, and chemically-defined alternative to serum albumin supplements, which have long represented a major source of biological contaminants and batch-to-batch variability in HSC cultures. Limiting dilution transplantation analysis of day-28 HSC cultures estimated a ~900-fold expansion of functional HSCs (based on >1% multilineage engraftment at 16-weeks post-transplantation) with secondary transplantation analysis estimating >200-fold expansion of serially-engraftable long-term HSCs. HSCs could also be expanded clonally using this system, demonstrating bone fide ex vivo HSC self-renewal. The large numbers of functional HSCs generated by this long-term ex vivo expansion system even enabled HSC transplantation in nonconditioned immunocompetent recipients. Finally, this albumin-free and GMP-compatible culture system also supported human HSCs ex vivo, as determined by long-term engraftment in NSG mice. Thus, our novel HSC culture system provides a useful platform to interrogate HSC self-renewal and lineage commitment and also suggests a novel approach in clinical HSC transplantation.

 

Related references:

  1. Wilkinson AC, Ishida R, Kikuchi M, Sudo K, Morita M, Crisostomo RV, Yamamoto R, Loh KM, Nakamura Y, Watanabe M, Nakauchi H, Yamazaki S. Long-term ex vivo hematopoietic-stem-cell expansion allows nonconditioned transplantation. Nature 2019. 571(7763):117-121.
  2. Wilkinson AC, Morita M, Nakauchi H, Yamazaki S. Branched-chain amino acid depletion conditions bone marrow for hematopoietic stem cell transplantation avoiding amino acid imbalance-associated toxicity. Experimental Hematology 2018. 63:12-16.

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