title: Cotransplantation of marrow stromal cells may prevent lethal graft-versus-host disease in major histocompatibility complex mismatched murine hematopoietic stem cell transplantation.
abstract: 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.
authors.affiliation: Department of Pediatrics, The Catholic University of Korea, College of Medicine, Seoul, Korea.
authors.forename: Nak Gyun
authors.initials: NG
authors.lastname: Chung
authors.forename: Dae Chul
authors.initials: DC
authors.lastname: Jeong
authors.forename: Soo Jeong
authors.initials: SJ
authors.lastname: Park
authors.forename: Byung Ock
authors.initials: BO
authors.lastname: Choi
authors.forename: Bin
authors.initials: B
authors.lastname: Cho
authors.forename: Hack Ki
authors.initials: HK
authors.lastname: Kim
authors.forename: Chung Sik
authors.initials: CS
authors.lastname: Chun
authors.forename: Jong Ho
authors.initials: JH
authors.lastname: Won
authors.forename: Chi Wha
authors.initials: CW
authors.lastname: Han
mesh_terms: 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*