Engraftment of W/c-kit mutant mice is determined by stem cell competition, not by increased marrow 'space'

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

W/c-kit mutant mice accept engraftment by small numbers of normal hematopoietic stem cells without the necessity for myeloablation. One explanation for this observation is that a deficiency of Kit receptors reduces the number of primitive hematopoietic stem cells and increases the number of available 'niches' or 'space' in the marrow. As a test of this model, we transplanted a series of unirradiated W mutant mice with donor marrow cells of the identical mutant genotype. Despite the intrinsic anemia and hematopoietic defect of severely affected W(x)/W(v) and mildly affected W(v) months after transplantation with 1-4 x 107 marrow cells of the same W(x)/W(v) and W(v)/+ genotypes, respectively. In contrast, both genotypes were engrafted, as judged by sustained proliferation of donor-derived RBC, after a second transplant with equal numbers of +/+ cells. The inability of W(x)/W(v) marrow to proliferate in W(x)/W(v) hosts was not due to an absence of transplantable stem cells, however, as W(x)/W(v) cells were capable of sustained engraftment and proliferation in irradiated W(x)/W(v) recipients. We conclude that when donor and host are equivalent for Kit receptor function, W mutant mice do not accept marrow grafts more readily than wild-type mice. The results suggest that a deficiency of host Kit receptor function promotes engraftment of normal stem cells not by increasing marrow space, but by providing an advantage to donor cells in competition for marrow stroma or for self-renewal and differentiation.

Original languageEnglish
Pages (from-to)209-213
Number of pages5
JournalExperimental Hematology
Volume24
Issue number2
StatePublished - 1996

Keywords

  • bone marrow transplantation
  • hematopoietic stem cells
  • proto-oncogene protein Kit
  • stromal cells

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Engraftment of W/c-kit mutant mice is determined by stem cell competition, not by increased marrow 'space''. Together they form a unique fingerprint.

Cite this