Hematopoietic stem cells (HSCs) are parent cells in the bone marrow that give rise to blood cells. Allogeneic stem cell transplantation has great potential in the treatment of malignancy, genetic disorders, and in solid organ transplantation. However, the radiation or high doses of chemotherapy commonly used in the treatment of blood cancers to destroy abnormal HSCs--a process called myeloablation-- is very toxic.
Furthermore, even following this form of conditioning, many patients develop graft-versus-host disease (GVHD), where the host immune system launches an attack against the newly transplanted HSCs.
In order to avoid both lethal conditioning and GVHD, new HSC transplant strategies are in development. Greiner et al. have adapted a costimulatory blockade-based protocol developed for solid organ transplantation for use in stem cell transplantation. The authors combined donor-specific transfusion and anti-CD154 monoclonal antibody administration to achieve functional donor and recipient HSC populations within the donor without the need for myeloablation or stimulating the induction of GVHD.
TITLE: Hematopoietic chimerism and central tolerance created by peripheral-tolerance induction without myeloablative conditioning
Dale L. Greiner
University of Massachusetts Medical School, Worcester, Massachusetts, USA
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