Purified Hematopoietic Stem Cells without Facilitating Cells can Repopulate Fully Allogeneic Recipients across Entire Major Histocompatibility Complex Transplantation Barrier in Mice

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 94; no. 26; pp. 14632 - 14636
• Main Authors: Wang, Bing-yan, El-Badri, Nagwa S., Good, Cherry, and Robert A.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 23-12-1997; National Acad Sciences; The National Academy of Sciences of the USA
• Subjects: Animals; Autoimmune diseases; Biological Sciences; Bone marrow; Bones; Cell Division; Cell Movement; Chimeras; Female; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - immunology; Major Histocompatibility Complex - immunology; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Spleen cells; Stem cells; Stromal cells; T lymphocytes; Thymectomy; Transplantation; Transplantation Immunology; Transplantation, Homologous
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.94.26.14632

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 bone marrow chimeras across the MHC barrier. In the present experiments, 1 × 105HSCs 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, FACS-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 × 104HSCs 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 × 104HSCs, 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.