J Korean Med Sci.  2007 Jun;22(3):412-419. 10.3346/jkms.2007.22.3.412.

Co-transplantation of Human Mesenchymal Stem Cells Promotes Human CD34+ Cells Engraftment in a Dose-dependent Fashion in NOD/SCID Mice

• Park SK
• Won JH
• Kim HJ
• Bae SB
• Kim CK
• Lee KT
• Lee NS
• Lee YK
• Jeong DC
• Chung NG
• Kim HS
• Hong DS
• Park HS

• KMID: 1778346
• DOI: http://doi.org/10.3346/jkms.2007.22.3.412

Abstract

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 1x10(5) human CD34+ cells in the presence or absence of culture expanded MSCs (1x10(6) or 5x10(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 cotransplanted 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 5x10(6) rather than 1x10(6) MSCs. These results suggest that MSCs are capable of enhancing hematopoietic cell engraftment and distribution in multiple organs in a dose-dependent fashion.

Keyword

Mesenchymal Stem Cells; Hematopoietic Stem Cells; Transplantation

MeSH Terms

Animals
Antigens, CD34/*biosynthesis
Cell Differentiation
Cells, Cultured
Dose-Response Relationship, Drug
Female
Fetal Blood/*metabolism
Humans
In Situ Hybridization, Fluorescence
Mesenchymal Stem Cells/*cytology
Mice
Mice, Inbred NOD
Mice, SCID
Microscopy, Fluorescence/methods
Stem Cell Transplantation/*methods

Figure

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  Fig. 1 Immunophenotype of cultured human mesenchymal stem cells. Mesenchymal stem cells expressed CD105 and CD166, but were negative for CD34, CD45, and CD14.

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  Fig. 2 Culture-expanded human mesenchymal stem cells exhibited a fibroblastic morphology (top panel). Under specific differentiation-inducing conditions, mesenchymal stem cells differentiated into osteoblasts, chondrocytes, and adipocytes.

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  Fig. 3 Effects of MSCs on human UCB 34+ cell engraftment in NOD/SCID mice. Co-transplantation with UCB CD34+ cells and MSCs resulted in higher engraftment levels in NOD/SCID mouse bone marrow 4 weeks after transplantation than after transplantation with UCB CD34+ cells alone. Moreover, this engraftment-promoting effect was related to the MSC dosage and increased myeloid and B lymphoid cell numbers but not those of T-lymphoid cells. *A significant difference (p<0.05) between the cotransplanted group and the group transplanted with CD34+ alone. †Significant (p<0.05) between the group infused with 1×106 MSCs and the group infused with 5×106 MSCs.

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  Fig. 4 Human X chromosome (green) and Y chromosome (red) expression by fluorescence in situ hybridization (FISH) analysis. Human X and Y chromosomes were detected in bone marrow, spleen, liver, lung, and kidney. Y chromosomes were detected in the heart, intestine, and skin (results of heart and intestine are not shown).

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