An in vivo model of double-unit cord blood transplantation that correlates with clinical engraftment.
Double-unit cord blood transplantation (DCBT) appears to enhance engraftment despite sustained hematopoiesis usually being derived from a single unit. To investigate DCBT biology, in vitro and murine models were established using cells from 39 patient grafts. Mononuclear cells (MNCs) and CD34(+) cells from each unit alone and in DCB combination were assessed for colony-forming cell and cobblestone area-forming cell potential, and multilineage engraftment in NOD/SCID/IL2R-γ(null) mice. In DCB assays, the contribution of each unit was measured by quantitative short tandem repeat region analysis. There was no correlation between colony-forming cell (n = 10) or cobblestone area-forming cell (n = 9) numbers and clinical engraftment, and both units contributed to DCB cocultures. In MNC transplantations in NOD/SCID/IL2R-γ(null) mice, each unit engrafted alone, but MNC DCBT demonstrated single-unit dominance that correlated with clinical engraftment in 18 of 21 cases (86%, P < .001). In contrast, unit dominance and clinical correlation were lost with CD34(+) DCBT (n = 11). However, add-back of CD34(-) to CD34(+) cells (n = 20) restored single-unit dominance with the dominant unit correlating not with clinical engraftment but also with the origin of the CD34(-) cells in all experiments. Thus, unit dominance is an in vivo phenomenon probably associated with a graft-versus-graft immune interaction mediated by CD34(-) cells.
Eldjerou
Lamis K
LK
Allogeneic Bone Marrow Transplantation, Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Chaudhury
Sonali
S
Baisre-de Leon
Ada
A
He
Mai
M
Arcila
Maria E
ME
Heller
Glenn
G
O'Reilly
Richard J
RJ
Barker
Juliet N
JN
Moore
Malcolm A
MA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003114:Colony-Forming Units Assay; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D005260:Female; D006082:Graft Enhancement, Immunologic / Q000379:methods*; D019337:Hematologic Neoplasms / Q000097:blood / Q000276:immunology / Q000628:therapy*; D006410:Hematopoiesis; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D051379:Mice; D008875:Middle Aged; D023421:Models, Animal; D014019:Tissue Donors; D014183:Transplantation, Heterologous; D055815:Young Adult
D018952:Antigens, CD34