Short-term culture of umbilical cord blood-derived CD34 cells enhances engraftment into NOD/SCID mice through increased CXCR4 expression.
Human umbilical cord blood (CB) has been used successfully in stem cell transplantation. A subpopulation of CD34(+) cells expresses chemokine receptor CXCR4 which is critical for bone marrow engraftment in human hematopoietic stem cells. Here, we demonstrate the effect of short-term culture on CXCR4 expression on umbilical CB-derived CD34(+) cells and subsequent engraftment capability in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. Surface CXCR4 expression on CD34(+) cells increased after incubating the cells in medium alone for 2 h; this effect was blocked by the addition of AMD3100. No difference in CXCR4 mRNA expression was noted after incubating CD34(+) cells in culture for 2 h, although these cells showed significantly increased transmigrational activity toward SDF-1 and homing activity in NOD/SCID mice. Furthermore, cultured human CD34(+) cells showed improved engraftment into the bone marrow of NOD/SCID mice compared to noncultured or AMD3100-treated CD34(+) cells. These observations suggest that increased cell surface expression of CXCR4 on CD34(+) cells improved the engraftment of human umbilical CB cells into bone marrow through enhanced homing activity.
Ohno
Norioki
N
Department of Pediatrics, Hiroshima University Graduate School of Biomedical Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima, Japan.
Kajiume
Teruyuki
T
Sera
Yasuhiko
Y
Sato
Takashi
T
Kobayashi
Masao
M
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D002465:Cell Movement; D002470:Cell Survival; D017690:Cell Transplantation; D002478:Cells, Cultured; D005312:Fetal Blood / Q000166:cytology* / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
D018952:Antigens, CD34; C527276:CXCR4 protein, human; D019718:Receptors, CXCR4