Cotransplantation of marrow stromal cells may prevent lethal graft-versus-host disease in major histocompatibility complex mismatched murine hematopoietic stem cell transplantation.
Marrow stromal cells (MSC) produce a microenvironment supporting hematopoiesis and may contribute immune tolerance because of low immunogenicity and the suppressive effect of alloreactivity. We investigated whether cotransplantation of MSC could prevent lethal graft-versus-host disease (GVHD) in major histocompatibility complex mismatched allogeneic murine hematopoietic stem cell transplantation (HSCT) using female BALB/c (H-2d, recipient) and C3H/He (H-2k, donor) mice. MSC were obtained from C3H/He bone marrow cells (BMC). MSC and irradiated BALB/c splenocytes (SP) were cocultured with C3H/He SP or BMC. Nonirradiated MSC did not inhibit the proliferation of alloantigen-stimulated BMC and SP. However, irradiated MSC suppressed the proliferation of alloantigen-stimulated SP at a level comparable with that of immunosuppressive agents, and the suppression by MSC was reversed to a significant degree by interleukin 2. Lethally irradiated BALB/c mice received transplants of donor cells according to the following experimental groups (group A, BMC only; group B, BMC and SP; group C, BMC, SP, and MSC; group D, BMC and MSC). The survival rate in group D was higher than in the other groups (P = .0057), and the clinical GVHD scores and serum levels of interferon-gamma were low in group D. Our results suggest that cotransplantation of MSC in HSCT prevents lethal GVHD, possibly by immune modulation.
Chung
Nak Gyun
NG
Department of Pediatrics, The Catholic University of Korea, College of Medicine, Seoul, Korea.
Jeong
Dae Chul
DC
Park
Soo Jeong
SJ
Choi
Byung Ock
BO
Cho
Bin
B
Kim
Hack Ki
HK
Chun
Chung Sik
CS
Won
Jong Ho
JH
Han
Chi Wha
CW
D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods*; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D008285:Major Histocompatibility Complex / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D017154:Stromal Cells / Q000637:transplantation*