Purified hematopoietic stem cells without facilitating cells can repopulate fully allogeneic recipients across entire major histocompatibility complex transplantation barrier in mice

被引:13
作者
Wang, BY [1 ]
El-Badri, NS [1 ]
Cherry [1 ]
Good, RA [1 ]
机构
[1] Univ S Florida, All Childrens Hosp, Dept Pediat, St Petersburg, FL 33701 USA
关键词
D O I
10.1073/pnas.94.26.14632
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
We report herein the successful long term engraftment of highly purified hematopoietic stem cells (HSCs) without any facilitating cells in fully allogeneic recipient mice across the entire major histocompatibility complex (MHC) transplantation barrier, This finding challenges the assumption that highly purified marrow HSCs alone cannot produce long-lived allogeneic hone marrow chimeras across the MHC barrier, In the present experiments, 1 x 10(5) HSCs from 5-fluorouracil (5-FU)-treated donors, without any facilitating cells, have been found to repopulate lethally irradiated fully allogeneic recipients, Low density, lineage-negative (CD4(-), CD8(-), B220(-), Mac-1(-), Gr-1(-)), CD71-negative, class I highly positive, FAGS-sorted cells from 5-FU-treated C57BL/6 (B6) donor mice were transplanted into lethally irradiated BALB/c recipients, (BALB/c --> BALB/c) --> BALB/c T cell depleted marrow cells used as compromised cells were also transplanted into the recipients to permit experiments to be pursued over a long period of time, Cells of donor origin in all recognized lineages of hematopoietic cells developed in these allogeneic chimeras, One thousand HSCs were sufficient to repopulate hemiallogeneic recipients, but 1 x 10(4) HSCs alone from 5-FU-treated donors failed to repopulate the fully allogeneic recipients, Transplantation of primary marrow stromal cells or bones of the donor strain into recipient, together with 1 x 10(4) HSCs, also failed to reconstitute fully allogeneic recipients, Suppression of resistance of recipients by thymectomy or injections of granulocyte colony-stimulating factor before stem cell transplantation enhanced the engraftment of allogeneic HSCs, Our experiments show that reconstitution of all lymphohematopoietic lineages across the entire MHC transplantation barriers may be achieved by transplanting allogeneic HSCs alone, without any facilitating cells, as long as a sufficient number of HSCs is transplanted.
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页码:14632 / 14636
页数:5
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