Article

International Journal of Hematology

, 80:370

First online:

Cotransplantation of Marrow Stromal Cells May Prevent Lethal Graft-versus-Host Disease in Major Histocompatibility Complex Mismatched Murine Hematopoietic Stem Cell Transplantation

  • Nak Gyun ChungAffiliated withDepartment of Pediatrics, Our Lady of Mercy Hospital
  • , Dae Chul JeongAffiliated withDepartment of Pediatrics, Our Lady of Mercy Hospital Email author 
  • , Soo Jeong ParkAffiliated withInternal Medicine, The Catholic University of Korea College of Medicine
  • , Byung Ock ChoiAffiliated withRadiation Oncology, The Catholic University of Korea College of Medicine
  • , Bin ChoAffiliated withDepartment of Pediatrics, Our Lady of Mercy Hospital
  • , Hack Ki KimAffiliated withDepartment of Pediatrics, Our Lady of Mercy Hospital
  • , Chung Sik ChunAffiliated withDepartment of Pediatrics, Our Lady of Mercy Hospital
  • , Jong Ho WonAffiliated withDepartment of Internal Medicine, Soonchunhyang University Medical College
  • , Chi Wha HanAffiliated withInternal Medicine, The Catholic University of Korea College of Medicine

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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-γ were low in group D. Our results suggest that cotransplantation of MSC in HSCT prevents lethal GVHD, possibly by immune modulation.

Key words

Marrow stromal cell Allogeneic hematopoietic stem cell transplantation Cell proliferation assay Interferon-γ