Elsevier

Transplantation Proceedings

Volume 42, Issue 7, September 2010, Pages 2753-2758
Transplantation Proceedings

Bone marrow/stem cell transplantation
Correlation Between the Immature Characteristics of Umbilical Cord Blood–Derived Mesenchymal Stem Cells and Engraftment of Hematopoietic Stem Cells in NOD/SCID Mice

https://doi.org/10.1016/j.transproceed.2010.05.146Get rights and content

Abstract

Umbilical cord blood (UCB)-derived mesenchymal stem cells (MSC) facilitate the engraftment of human (h) hematopoietic stem cells when transplanted simultaneously in animal and human studies. However, the type of MSCs that preferentially enhance the engraftment of HSCs is unknown. Recent studies have shown that MSCs derived from a single source are heterogeneous in terms of cell size, morphology, proliferation rate, and differentiation potential.

This study was designed to investigate the properties of UCB-MSCs, which influence the engraftment of hHSCs in a NOD/SCID mouse model. We categorized MSCs as being the most effective (UCB-352 MSCs) or the least effective (UCB-156 MSCs) at promoting the homing and engraftment of HSCs, and compared the characteristics of these 2 MSC populations. We observed that the 2 populations showed differences in characteristics typical of immature MSCs, and related to proliferation potential. We showed that UCB-352 MSCs, which proliferate quickly, preferentially enhanced the engraftment of HSCs in NOD/SCID mice. In addition, we observed differences in the pattern of both PODXL and Oct4 expression, and in the levels of cytokines such as SDF-1 and SCF using flow cytometry and membrane arrays. The more effective UCB-352 MSCs expressed higher levels of PODXL and Oct4, which were associated with immaturity, than did the UCB-156 MSCs. Furthermore, UCB-352 cells secreted greater levels of SDF-1 and SCF, both of which are required for hematopoiesis. We propose that the proliferation potential of UCB-MSCs, coupled with their immature characteristics, may serve as a novel standard to promote the homing and engraftment of HSCs.

Section snippets

Isolation of CD34+ Cells From UCB

UCB was obtained from the umbilical cords of full-term deliveries after receiving informed consent. UCB collected in bags containing heparin were processed within 24 hours. After separation over Ficoll-Hypaque (Histopaque-1077; Sigma, St Louis, MO), low-density cells were washed in RPMI-1640 (Gibco-Invitrogen, Grand Isle, NY) supplemented with penicillin (20 U/mL; Gibco-Invitrogen), streptomycin (20 μg/mL; Gibco-Invitrogen), and 2% heat-inactivated fetal calf serum. CD34+ cells were isolated

Results

To identify the effects of UCB-MSCs on the homing and engraftment of hHSCs, we intravenously infused both MSCs and CD34+ HSCs into NOD/SCID mice. We successfully isolated UCB-MSCs from various donors and cultured them until passage 4. FACS analysis showed these cells to be positive for typical MSC antigens (CD29, CD44, CD105, CD166), but negative for typical hematopoietic antigens (CD14, CD34, CD45), and HLA-DR (MHC class II), indicating that they were MSCs (Fig 1A, B). Also, expanded UCB-MSCs

Discussion

The major finding of this study was that the UCB-MSCs that were most effective in promoting the engraftment of hHSCs were characterized by an immature phenotype. We systemically injected various populations of human UCB-derived MSCs into NOD/SCID mice after irradiation. The aim of our study was to evaluate the capacity of UCB-MSCs to promote the engraftment of hHSCs in these mice. However, our results showed that the ability of UCB-MSCs to promote engraftment is host dependent. To identify the

Acknowledgments

Y.S.Y. and Y.H.N. contributed equally to this work.

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    Y.S.Y and Y.H.N contributed equally to this work.

    Supported by a grant from the national R&D program for Cancer control, Ministry for Health, Welfare and Family affairs, Republic of Korea (Project No: 0720230) and by Samsung Biomedical Research Institute grant, #SBRI C-A7-201-3.

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