Transplantation of Mesenchymal Stem Cells Promotes Tissue Regeneration in a Glaucoma Model Through Laser-Induced Paracrine Factor Secretion and Progenitor Cell Recruitment§

Authors

  • Renaud Manuguerra-GagnÉ,

    1. Division of Hematology-Oncology, Hopital Maisonneuve-Rosemont Research Center, Montreal, Canada
    2. Department of Vision Health Research, Hopital Maisonneuve-Rosemont, Montreal, Canada
    3. Department of Medicine, University of Montreal, Montreal, Canada
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  • Patrick R. Boulos,

    1. Department of Vision Health Research, Hopital Maisonneuve-Rosemont, Montreal, Canada
    2. Department of Ophthalmology, University of Montreal, Montreal, Canada
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  • Ahmed Ammar,

    1. Division of Hematology-Oncology, Hopital Maisonneuve-Rosemont Research Center, Montreal, Canada
    2. Department of Vision Health Research, Hopital Maisonneuve-Rosemont, Montreal, Canada
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  • François A. Leblond,

    1. Division of Nephrology, Hopital Maisonneuve-Rosemont Research Center, Montreal, Canada
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  • Gorazd Krosl,

    1. Division of Hematology-Oncology, Hopital Maisonneuve-Rosemont Research Center, Montreal, Canada
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  • Vincent Pichette,

    1. Department of Medicine, University of Montreal, Montreal, Canada
    2. Division of Nephrology, Hopital Maisonneuve-Rosemont Research Center, Montreal, Canada
    3. Department of Pharmacology, University of Montreal, Montreal, Canada
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  • Mark R. Lesk,

    Corresponding author
    1. Department of Vision Health Research, Hopital Maisonneuve-Rosemont, Montreal, Canada
    2. Department of Ophthalmology, University of Montreal, Montreal, Canada
    • Glaucoma Research Laboratory, Hopital Maisonneuve-Rosemont Research Center, 5415 l'Assomption blvd., Montreal, Quebec H1T 2M4, Canada
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    • Telephone: 514-252-3400, ext. 4959; Fax : 514-251-7094

  • Denis-Claude Roy

    Corresponding author
    1. Division of Hematology-Oncology, Hopital Maisonneuve-Rosemont Research Center, Montreal, Canada
    2. Department of Medicine, University of Montreal, Montreal, Canada
    • Cellular Therapy Laboratory, Hospital Maisonneuve-Rosemont Research Center, 5415 l'Assomption blvd., Montreal, Quebec H1T 2M4, Canada
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    • Telephone: 514-252-3400, ext.3331; Fax: 514-252-3430


  • Author contributions: R.M.-G.: conception and design, collection and/or assembly of data, data analysis and interpretation, and manuscript writing; P.R.B. and V.P.: conception and design; A.A. and F.A.L.: conception and design and collection and/or assembly of data; G.K.: conception and design and manuscript writing; M.R.L. and D.-C.R.: conception and design, administrative support, financial support, manuscript writing.

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

  • §

    first published online in STEM CELLS EXPRESS February 4, 2013.

Abstract

Among bone marrow cells, hematopoietic and mesenchymal components can contribute to repair damaged organs. Such cells are usually used in acute diseases but few options are available for the treatment of chronic disorders. In this study, we have used a laser-induced model of open angle glaucoma (OAG) to evaluate the potential of bone marrow cell populations and the mechanisms involved in tissue repair. In addition, we investigated laser-induced tissue remodeling as a method of targeting effector cells into damaged tissues. We demonstrate that among bone marrow cells, mesenchymal stem cells (MSC) induce trabecular meshwork regeneration. MSC injection into the ocular anterior chamber leads to far more efficient decrease in intraocular pressure (IOP) (p < .001) and healing than hematopoietic cells. This robust effect was attributable to paracrine factors from stressed MSC, as injection of conditioned medium from MSC exposed to low but not to normal oxygen levels resulted in an immediate decrease in IOP. Moreover, MSC and their secreted factors induced reactivation of a progenitor cell pool found in the ciliary body and increased cellular proliferation. Proliferating cells were observed within the chamber angle for at least 1 month. Laser-induced remodeling was able to target MSC to damaged areas with ensuing specific increases in ocular progenitor cells. Thus, our results identify MSC and their secretum as crucial mediators of tissue repair in OAG through reactivation of local neural progenitors. In addition, laser treatment could represent an appealing strategy to promote MSC-mediated progenitor cell recruitment and tissue repair in chronic diseases. STEM Cells 2013;31:1136–1148

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