title: Cotransplanted bone marrow derived mesenchymal stem cells (MSC) enhanced engraftment of hematopoietic stem cells in a MSC-dose dependent manner in NOD/SCID mice.
abstract: Transplantation of marrow-derived mesenchymal stem cells (MSCs), expanded by culture in addition to whole bone marrow, has been shown to enhance engraftment of human hematopoietic stem cells (HSCs). Our hypothesis was that there might be an optimum ratio range that could enhance engraftment. We examined the percent donor chimerism according to the ratio of HSCs to MSCs in non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice. We tested a series of ratios of co-transplanted CD34(+) -selected bone marrow cells, and marrow-derived MSCs into sublethally irradiated NOD/SCID mice. In all experiments, 1x10(5) bone marrow derived human CD34(+) cells were administered to each mouse and human MSCs from different donors were infused concomitantly. We repeated the procedure three times and evaluated engraftment with flow cytometry four weeks after each transplantation. Serial ratios of HSCs to MSCs were 1:0, 1:1, 1:2 and 1:4, in the first experiment, 1:0, 1:1, 1:2, 1:4 and 1:8 in the second and 1:0, 1:1, 1:4, 1:8 and 1:16 in the third. Cotransplantation of HSCs and MSCs enhanced engraftment as the dose of MSCs increased. Our results suggest that the optimal ratio of HSCs and MSCs for cotransplantation might be in the range of 1:8-1:16; whereas, an excessive dose of MSCs might decrease engraftment efficiency.
authors.affiliation: School of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Keon Hee
authors.initials: KH
authors.lastname: Yoo
authors.forename: Young Sook
authors.initials: YS
authors.lastname: Yim
authors.forename: Jaewon
authors.initials: J
authors.lastname: Choi
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Lee
authors.forename: Hye Lim
authors.initials: HL
authors.lastname: Jung
authors.forename: Ki Woong
authors.initials: KW
authors.lastname: Sung
authors.forename: Sung-Eun
authors.initials: SE
authors.lastname: Yang
authors.forename: Won Il
authors.initials: WI
authors.lastname: Oh
authors.forename: Yoon-Sun
authors.initials: YS
authors.lastname: Yang
authors.forename: Sang-Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Sang-Yun
authors.initials: SY
authors.lastname: Choi
authors.forename: Hong Hoe
authors.initials: HH
authors.lastname: Koo
mesh_terms: D000328:Adult; D000818:Animals; D002452:Cell Count; D002478:Cells, Cultured; D006085:Graft Survival / Q000502:physiology*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged