Lymphohematopoietic stem cell engraftment

Peter J. Quesenberry, F. Marc Stewart, Suju Zhong, Houri Habibian, Christina McAuliffe, Judy Reilly, Jane Carlson, Mark Dooner, Susie Nilsson, Stefan Peters, Gary Stein, Janet Stein, Rob Emmons, Brian Benoit, Ivan Bertoncello, Pamela Becker

Research output: Contribution to journalArticleResearchpeer-review

13 Citations (Scopus)

Abstract

Traditional dogma has stated that space needs to be opened by cytoxic myeloablative therapy in order for marrow stem cells to engraft. Resent work in murine transplant models, however, indicates that engraftment is determined by the ratio of donor to host stem cells, i.e., stem cell competition. One hundred centigray whole body irradiation is stem cell toxic and nonmyelotoxic, thus allowing for higher donor chimerism in a murine syngeneic transplant setting. This nontoxic stem cell transplantation can be applied to allogeneic transplant with the addition of a tolerizing step; in this case presensitization with donor spleen cells and administration of CD40 ligand antibody to block costimulation. The stem cells that engraft in the nonmyeloablated are in G0, but are rapidly induced (by 12 hours) to enter the S phase after in vivo engraftment. Exposure of murine marrow to cytokines (IL-3, IL-6, IL-11 and steel factor) expands progenitor clones, induces stem cells into cell cycle, and causes a fluctuating engraftment phenotype tied to phase of cell cycle. These data indicate that the concepts of stem cell competition and fluctuation of stem cell phenotype with cell cycle transit should underlie any new stem cell engraftment strategy.

Original languageEnglish
Pages (from-to)40-47
Number of pages8
JournalAnnals of the New York Academy of Sciences
Volume872
DOIs
Publication statusPublished - 1999
Externally publishedYes

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