Superior Osteogenic Capacity for Bone Tissue Engineering of Fetal Compared with Perinatal and Adult Mesenchymal Stem Cells§

Authors

  • Zhi-Yong Zhang,

    1. Graduate Program in Bioengineering, National University of Singapore, Singapore
    2. Centre for Biomedical Materials Applications and Technology (BIOMAT), Department of Mechanical Engineering, Faculty of Engineering, National University of Singapore, Singapore
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  • Swee-Hin Teoh,

    1. Centre for Biomedical Materials Applications and Technology (BIOMAT), Department of Mechanical Engineering, Faculty of Engineering, National University of Singapore, Singapore
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  • Mark S.K. Chong,

    1. Graduate Program in Bioengineering, National University of Singapore, Singapore
    2. Centre for Biomedical Materials Applications and Technology (BIOMAT), Department of Mechanical Engineering, Faculty of Engineering, National University of Singapore, Singapore
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  • Jan Thorsten Schantz,

    1. Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore and National University Hospital Systems, Singapore
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  • Nicholas M. Fisk,

    1. The University of Queensland Centre for Clinical Research, Brisbane, Australia
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  • Mahesh A. Choolani,

    Corresponding author
    1. Experimental Fetal Medicine Group, Department of Obstetrics & Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore and National University Hospital Systems, Singapore
    • Experimental Fetal Medicine Group, Department of Obstetrics & Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore and National University Hospital Systems, Singapore 119074

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    • Telephone: 65-6772-4261; Fax: 65-6779-4753

  • Jerry Chan

    1. Experimental Fetal Medicine Group, Department of Obstetrics & Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore and National University Hospital Systems, Singapore
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  • Author contributions: Z.Y.Z.: design of the study, collection, analysis, and interpretation of data, manuscript writing; T.S.H.: conception and design of the study, provision of study material, analysis and interpretation of data, manuscript writing; M.C.: provision of study material, analysis and interpretation of data, manuscript writing; J.T.S.: provision of study material; N.M.F.: analysis of data, manuscript writing; M.C.: conception and design, financial support, administrative support, provision of study materials, analysis of data, manuscript writing, final approval of the manuscript; J.C.: conception and design, financial support, administrative support, provision of study materials, analysis of data, manuscript writing, final approval of the manuscript; M.A.C. and J.C. contributed equally to this work.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLS Express October 2, 2008.

Abstract

Mesenchymal stem cells (MSCs) from human adult bone marrow (haMSCs) represent a promising source for bone tissue engineering. However, their low frequencies and limited proliferation restrict their clinical utility. Alternative postnatal, perinatal, and fetal sources of MSCs appear to have different osteogenic capacities, but have not been systematically compared with haMSCs. We investigated the proliferative and osteogenic potential of MSCs from human fetal bone marrow (hfMSCs), human umbilical cord (hUCMSCs), and human adult adipose tissue (hATMSCs), and haMSCs, both in monolayer cultures and after loading into three-dimensional polycaprolactone-tricalcium-phosphate scaffolds.Although all MSCs had comparable immunophenotypes, only hfMSCs and hUCMSCs were positive for the embryonic pluripotency markers Oct-4 and Nanog. hfMSCs expressed the lowest HLA-I level (55% versus 95%–99%) and the highest Stro-1 level (51% versus 10%–27%), and had the greatest colony-forming unit–fibroblast capacity (1.6×–2.0×; p < .01) and fastest doubling time (32 versus 54–111 hours; p < .01). hfMSCs had the greatest osteogenic capacity, as assessed by von-Kossa staining, alkaline phosphatase activity (5.1×–12.4×; p < .01), calcium deposition (1.6×–2.7× in monolayer and 1.6×–5.0× in scaffold culture; p < .01), calcium visualized on micro-computed tomography (3.9×17.6×; p < .01) and scanning electron microscopy, and osteogenic gene induction. Two months after implantation of cellular scaffolds in immunodeficient mice, hfMSCs resulted in the most robust mineralization (1.8×–13.3×; p < .01).The ontological and anatomical origins of MSCs have profound influences on the proliferative and osteogenic capacity of MSCs. hfMSCs had the most proliferative and osteogenic capacity of the MSC sources, as well as being the least immunogenic, suggesting they are superior candidates for bone tissue engineering. STEM CELLS 2009;27:126–137

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