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Lymphohematopoietic Stem Cell Engraftment a
Author(s) -
QUESENBERRY PETER J.,
STEWART F. MARC,
ZHONG SUJU,
HABIBIAN HOURI,
MCAULIFFE CHRISTINA,
REILLY JUDY,
CARLSON JANE,
DOONER MARK,
NILSSON SUSIE,
PETERS STEFAN,
STEIN GARY,
STEIN JANET,
EMMONS ROB,
BENOIT BRIAN,
BERTONCELLO IVAN,
BECKER PAMELA
Publication year - 1999
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1999.tb08451.x
Subject(s) - stem cell , haematopoiesis , progenitor cell , immunology , transplantation , stem cell factor , biology , induced pluripotent stem cell , bone marrow , cancer research , microbiology and biotechnology , medicine , embryonic stem cell , genetics , gene
A bstract : Traditional dogma has stated that space needs to be opened by cytoxic myeloablative therapy in order for marrow stem cells to engraft. Recent 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 G 0 , 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.