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Published Online: 12 September 2013

Potential of Human Fetal Chorionic Stem Cells for the Treatment of Osteogenesis Imperfecta

Publication: Stem Cells and Development
Volume 23, Issue Number 3

Abstract

Osteogenesis imperfecta (OI) is a genetic bone pathology with prenatal onset, characterized by brittle bones in response to abnormal collagen composition. There is presently no cure for OI. We previously showed that human first trimester fetal blood mesenchymal stem cells (MSCs) transplanted into a murine OI model (oim mice) improved the phenotype. However, the clinical use of fetal MSC is constrained by their limited number and low availability. In contrast, human fetal early chorionic stem cells (e-CSC) can be used without ethical restrictions and isolated in high numbers from the placenta during ongoing pregnancy. Here, we show that intraperitoneal injection of e-CSC in oim neonates reduced fractures, increased bone ductility and bone volume (BV), increased the numbers of hypertrophic chondrocytes, and upregulated endogenous genes involved in endochondral and intramembranous ossification. Exogenous cells preferentially homed to long bone epiphyses, expressed osteoblast genes, and produced collagen COL1A2. Together, our data suggest that exogenous cells decrease bone brittleness and BV by directly differentiating to osteoblasts and indirectly stimulating host chondrogenesis and osteogenesis. In conclusion, the placenta is a practical source of stem cells for the treatment of OI.

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Information & Authors

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Published In

cover image Stem Cells and Development
Stem Cells and Development
Volume 23Issue Number 3February 1, 2014
Pages: 262 - 276
PubMed: 24028330

History

Published in print: February 1, 2014
Published ahead of print: 16 October 2013
Published online: 12 September 2013
Accepted: 12 September 2013
Received: 11 March 2013

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    Affiliations

    Gemma N. Jones
    *
    Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom.
    Dafni Moschidou*
    Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom.
    Hassan Abdulrazzak
    Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom.
    Bhalraj Singh Kalirai
    Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom.
    Maximilien Vanleene
    Department of Bioengineering, Imperial College London, London, United Kingdom.
    Suchaya Osatis
    Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom.
    Sandra J. Shefelbine
    Department of Bioengineering, Imperial College London, London, United Kingdom.
    Nicole J. Horwood
    Kennedy Institute of Rheumatology, Imperial College London, London, United Kingdom.
    Massimo Marenzana
    Department of Bioengineering, Imperial College London, London, United Kingdom.
    Paolo De Coppi
    Surgery Unit, UCL Institute of Child Health, London, United Kingdom.
    J.H. Duncan Bassett
    Molecular Endocrinology Group, Department of Medicine, Imperial College London, London, United Kingdom.
    Graham R. Williams
    Molecular Endocrinology Group, Department of Medicine, Imperial College London, London, United Kingdom.
    Nicholas M. Fisk
    UQ Centre for Clinical Research, University of Queensland, Brisbane, Australia.
    Pascale V. Guillot
    Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom.

    Notes

    Address correspondence to:Dr. Pascale V. GuillotInstitute of Reproductive and Developmental BiologyImperial College LondonDu Cane RoadLondon W12 0NNUnited Kingdom
    E-mail: [email protected]

    Author Disclosure Statement

    The authors declare no competing financial interests exist.

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