title: Multiple allogeneic progenitors in combination function as a unit to support early transient hematopoiesis in transplantation.
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.
authors: 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.
authors: Takashi
authors: 0000-0002-9429-1763
authors: T
authors: Ishida
authors: Division of Molecular Therapy, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo 108-0071, Japan.
authors: Satoshi
authors: S
authors: Takahashi
authors: Division of Stem Cell Processing, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-0071, Japan.
authors: Chen-Yi
authors: CY
authors: Lai
authors: Division of Advanced Medicine Promotion, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo 108-0071, Japan.
authors: Masanori
authors: M
authors: Nojima
authors: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305.
authors: Ryo
authors: R
authors: Yamamoto
authors: Department of Immunology, Kitasato University Graduate School of Medical Science, Kanagawa 252-0374, Japan.
authors: Emiko
authors: 0000-0001-7623-6261
authors: E
authors: Takeuchi
authors: Department of Nephrology, Kitasato University School of Medicine, Kanagawa 252-0374, Japan.
authors: Yasuo
authors: Y
authors: Takeuchi
authors: Department of Hematology, Kitasato University School of Medicine, Kanagawa 252-0374, Japan.
authors: Masaaki
authors: M
authors: Higashihara
authors: 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.
authors: Hiromitsu
authors: H
authors: Nakauchi
authors: 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.
authors: Makoto
authors: 0000-0002-9769-0217
authors: M
authors: Otsu
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D036101:Cord Blood Stem Cell Transplantation; D006410:Hematopoiesis; D051379:Mice; D008815:Mice, Inbred Strains; D011835:Radiation Protection; D013601:T-Lymphocytes / Q000276:immunology; D018183:Transplantation Chimera; D014184:Transplantation, Homologous
chemical_list: D018952:Antigens, CD34