Format

Send to

Choose Destination
J Exp Med. 2016 Aug 22;213(9):1865-80. doi: 10.1084/jem.20151493. Epub 2016 Aug 8.

Multiple allogeneic progenitors in combination function as a unit to support early transient hematopoiesis in transplantation.

Author information

1
Department of Hematology, Kitasato University School of Medicine, Kanagawa 252-0374, Japan Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-0071, Japan.
2
Division of Molecular Therapy, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo 108-0071, Japan.
3
Division of Stem Cell Processing, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-0071, Japan.
4
Division of Advanced Medicine Promotion, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo 108-0071, Japan.
5
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305.
6
Department of Immunology, Kitasato University Graduate School of Medical Science, Kanagawa 252-0374, Japan.
7
Department of Nephrology, Kitasato University School of Medicine, Kanagawa 252-0374, Japan.
8
Department of Hematology, Kitasato University School of Medicine, Kanagawa 252-0374, Japan.
9
Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-0071, Japan Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305.
10
Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-0071, Japan Division of Stem Cell Processing, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-0071, Japan motsu@ims.u-tokyo.ac.jp.

Abstract

Cord blood (CB) is a valuable donor source in hematopoietic cell transplantation. However, the initial time to engraftment in CB transplantation (CBT) is often delayed because of low graft cell numbers. This limits the use of CB. To overcome this cell dose barrier, we modeled an insufficient dose CBT setting in lethally irradiated mice and then added hematopoietic stem/progenitor cells (HSCs/HPCs; HSPCs) derived from four mouse allogeneic strains. The mixture of HSPCs rescued recipients and significantly accelerated hematopoietic recovery. Including T cells from one strain favored single-donor chimerism through graft versus graft reactions, with early hematopoietic recovery unaffected. Furthermore, using clinically relevant procedures, we successfully isolated a mixture of CD34(+) cells from multiple frozen CB units at one time regardless of HLA-type disparities. These CD34(+) cells in combination proved transplantable into immunodeficient mice. This work provides proof of concept that when circumstances require support of hematopoiesis, combined multiple units of allogeneic HSPCs are capable of early hematopoietic reconstitution while allowing single-donor hematopoiesis by a principal graft.

PMID:
27503070
PMCID:
PMC4995077
DOI:
10.1084/jem.20151493
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center