title: Ex vivo expanded hematopoietic stem cells overcome the MHC barrier in allogeneic transplantation.
abstract: The lack of understanding of the interplay between hematopoietic stem cells (HSCs) and the immune system has severely hampered the stem cell research and practice of transplantation. Major problems for allogeneic transplantation include low levels of donor engraftment and high risks of graft-versus-host disease (GVHD). Transplantation of purified allogeneic HSCs diminishes the risk of GVHD but results in decreased engraftment. Here we show that ex vivo expanded mouse HSCs efficiently overcame the major histocompatibility complex barrier and repopulated allogeneic-recipient mice. An 8-day expansion culture led to a 40-fold increase of the allograft ability of HSCs. Both increased numbers of HSCs and culture-induced elevation of expression of the immune inhibitor CD274 (B7-H1 or PD-L1) on the surface of HSCs contributed to the enhancement. Our study indicates the great potential of utilizing ex vivo expanded HSCs for allogeneic transplantation and suggests that the immune privilege of HSCs can be modulated.
authors.affiliation: Department of Physiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
authors.forename: Junke
authors.initials: J
authors.lastname: Zheng
authors.forename: Masato
authors.initials: M
authors.lastname: Umikawa
authors.forename: Shichuan
authors.initials: S
authors.lastname: Zhang
authors.forename: HoangDinh
authors.initials: H
authors.lastname: Huynh
authors.forename: Robert
authors.initials: R
authors.lastname: Silvany
authors.forename: Benjamin P C
authors.initials: BP
authors.lastname: Chen
authors.forename: Lieping
authors.initials: L
authors.lastname: Chen
authors.forename: Cheng Cheng
authors.initials: CC
authors.lastname: Zhang
mesh_terms: D000818:Animals; D060890:B7-H1 Antigen / Q000378:metabolism; D002452:Cell Count; D002462:Cell Membrane / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D055879:Gene Knock-In Techniques; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology*; D006801:Humans; D008285:Major Histocompatibility Complex / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D014184:Transplantation, Homologous; D015854:Up-Regulation
chemical_list: D060890:B7-H1 Antigen