title: Chimerism of bone marrow mesenchymal stem/stromal cells in allogeneic hematopoietic cell transplantation: is it clinically relevant?
abstract: Multipotent mesenchymal stem/stromal cells (MSCs) have been extensively used as a transplantable cell source for regenerative medicine and immunomodulatory therapy. Specifically in allogeneic hematopoietic stem cell transplantation (HSCT), co-transplantation or post-transplant infusion of MSCs derived from bone marrow (BM) of non-self donors has been implicated in accelerating hematopoietic recovery, ameliorating graft-vs.-host disease, and promoting tissue regeneration. However, irrespective of the use of MSC co-administration, post-transplant chimerism of BM-derived MSCs after allogeneic HSCT has been reported to remain of host origin, suggesting that the infused donor MSCs are immunologically rejected or not capable of long-term engraftment in the host microenvironment. Also, hematopoietic cell allografts currently used for HSCT do not seem to contain sufficient amount of MSCs or their precursors to reconstitute host BM microenvironment. Since the toxic conditioning employed in allo-HSCT may impair the function of host MSCs to maintain hematopoietic/regenerative stem cell niches and to provide a local immunomodulatory milieu, we propose that new directions for enhancing immunohematopoietic reconstitution and tissue repair after allogeneic HSCT include the development of strategies to support functional replenishment of residual host MSCs or to support more efficient engraftment of infused donor MSCs. Future areas of research should include in vivo tracking of infused MSCs and detection of their microchimeric presence in extra-marrow sites as well as in BM.
authors.affiliation: Department of Transfusion Medicine and Cell Therapy; Kyoto University Hospital; Kyoto, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Miura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yoshioka
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Yao
authors.forename: Akifumi
authors.initials: A
authors.lastname: Takaori-Kondo
authors.forename: Taira
authors.initials: T
authors.lastname: Maekawa
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Ichinohe
mesh_terms: D001853:Bone Marrow / Q000276:immunology; D060833:Cellular Microenvironment / Q000276:immunology; D046528:Chimerism; D006086:Graft vs Host Disease / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007154:Immune System Diseases / Q000628:therapy; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology* / Q000502:physiology; D012038:Regeneration; D019172:Transplantation Conditioning; D023001:Transplantation Tolerance / Q000276:immunology*; D014184:Transplantation, Homologous
keywords: graft-versus-host disease; hematopoietic cell transplantation; hematopoietic reconstitution; mesenchymal stem/stromal cells; stem cell niches