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

作者：Ishida Takashi; Takahashi Satoshi; Lai Chen Yi; Nojima Masanori; Yamamoto Ryo; Takeuchi Emiko; Takeuchi Yasuo; Higashihara Masaaki; Nakauchi Hiromitsu; Otsu Makoto^*

来源：Journal of Experimental Medicine, 2016, 213(9): 1865-1880.

DOI：10.1084/jem.20151493

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.

• 出版日期2016-8-22
• 单位河北医科大学