title: 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.
authors.affiliation: Division of Hematology-Oncology, Hopital Maisonneuve-Rosemont Research Center, Montreal, Canada.
authors.forename: Renaud
authors.initials: R
authors.lastname: Manuguerra-Gagné
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Boulos
authors.forename: Ahmed
authors.initials: A
authors.lastname: Ammar
authors.forename: François A
authors.initials: FA
authors.lastname: Leblond
authors.forename: Gorazd
authors.initials: G
authors.lastname: Krosl
authors.forename: Vincent
authors.initials: V
authors.lastname: Pichette
authors.forename: Mark R
authors.initials: MR
authors.lastname: Lesk
authors.forename: Denis-Claude
authors.initials: DC
authors.lastname: Roy
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D002924:Ciliary Body / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D005901:Glaucoma / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019899:Paracrine Communication; D051381:Rats; D011914:Rats, Inbred BN; D012038:Regeneration / Q000502:physiology*; D014129:Trabecular Meshwork / Q000502:physiology