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

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

Stem Cells in the Trabecular Meshwork for Regulating Intraocular Pressure

“…53,54 Bone marrow-derived mesenchymal stem cells are multipotent and have been explored for TM regeneration. 55 In the study by Manuguerra-Gagne et al, 55 MSCs were injected into the anterior chamber of rats with laser-induced glaucoma. MSC injection induced a rapid return to normal IOP levels in experimental glaucomatous rats.…”

Editorial: 2013—A Year of Clinical Success and Great Scientific Innovation in the Stem Cell Field

“…Manuscripts covered many advances in understanding the fundamental mechanisms that control stem and progenitor cell fate, and advances in working toward treating all tissues, from the lower extremities to the brain. Exciting basic and translational research was reported in using stem cells to treat osteoporosis [11], spinal cord injuries [12,13], radiation-induced fibrosis [14], glaucoma [15], globoid cell leukodystrophy [16], stroke [17], and Huntington's disease [18], to name just a few. It has truly been an exciting year, as we watch the stem cell field explode.…”

Cell therapy using retinal progenitor cells shows therapeutic effect in a chemically-induced rotenone mouse model of Leber hereditary optic neuropathy

“…This can be shown to be the case with photoreceptor transplants, 13 but may not be the case for other stem cells delivered to other sites in the body, with a paracrine mode of action favoured for some. [26][27][28] In this case, the premise is that secretion of hormones, growth factors and/or extracellular matrix components by the stem cells, in complex dialogue with pre-existing damaged tissue, may be stimulating transplanted cells to secrete therapeutic substances in response to the injured host tissue, thereby providing benefit. [26][27][28] The addition of pRPCs with glial potential to damaged retinas may enhance natural repair processes, by physical contact and structural repair, by providing an antiapoptotic effect (as suggested by increased Bcl2 levels), and by secretion of hormones and/or growth factors [26][27][28] or, perhaps, via increased glial protection of normally unmyelinated segments of ganglion cell axons.…”