Co-transplantation of human mesenchymal stem cells promotes human CD34+ cells engraftment in a dose-dependent fashion in NOD/SCID mice.
Mesenchymal stem cells (MSCs) have recently been identified and characterized in humans. Moreover, MSC secrete cytokines that can support hematopoietic progenitor growth. In the present study, we evaluated whether the efficacy of hematopoietic stem cell transplantation is improved by their co-transplantation with MSC, and whether this is positively correlated with the dose of infused MSCs. Accordingly, irradiated NOD/SCID mice were transplanted with 1 x 10(5) human CD34+ cells in the presence or absence of culture expanded MSCs (1 x 10(6) or 5 x 10(6)). We evaluated human hematopoietic cell engraftment by flow cytometry and assessed MSC tissue distributions by fluorescence in situ hybridization. We found that CD45+ and CD34+ cell levels were significantly elevated in a dose-dependent manner in co-transplanted mice 4 weeks after transplantation. The engraftments of CD33+ and CD19+ cells also increased dose-dependently. However, the engraftment of CD3+ cells did not increase after co-transplantation with MSCs. Human Y chromosome+ cells were observed in multiple tissues and were more frequently observed in mice co-transplanted with 5 x 10(6) rather than 1 x 10(6) MSCs. These results suggest that MSCs are capable of enhancing hematopoietic cell engraftment and distribution in multiple organs in a dose-dependent fashion.
Park
Seong-Kyu
SK
Department of Internal Medicine, Soon Chun Hyang University College of Medicine, Seoul, Korea.
Won
Jong-Ho
JH
Kim
Hyun-Jung
HJ
Bae
Sang-Byung
SB
Kim
Chan-Kyu
CK
Lee
Kyu-Taeg
KT
Lee
Nam-Su
NS
Lee
You Kyoung
YK
Jeong
Dae-Chul
DC
Chung
Nak-Gyun
NG
Kim
Hyun-Soo
HS
Hong
Dae-Sik
DS
Park
Hee-Sook
HS
D000818:Animals; D018952:Antigens, CD34 / Q000096:biosynthesis*; D002454:Cell Differentiation; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D005312:Fetal Blood / Q000378:metabolism*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008856:Microscopy, Fluorescence / Q000379:methods; D033581:Stem Cell Transplantation / Q000379:methods*
D018952:Antigens, CD34