Transplantation of Mesenchymal Stem Cells Promotes Tissue Regeneration in a Glaucoma Model Through Laser-Induced Paracrine Factor Secretion and Progenitor Cell Recruitment
Transplantation of Mesenchymal Stem Cells Promotes Tissue Regeneration in a Glaucoma Model Through Laser-Induced Paracrine Factor Secretion and Progenitor Cell Recruitment
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DOI：
10.1002/stem.1364
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发表时间：
2013-06-01
期刊：
影响因子：
5.2
通讯作者：
Roy, Denis-Claude
中科院分区：
文献类型：
--
作者：
Manuguerra-Gagne, Renaud;Boulos, Patrick R.;Roy, Denis-Claude
在骨髓细胞中，造血和间充质成分有助于修复受损器官。这些细胞通常用于急性疾病，但用于治疗慢性疾病的选择很少。在这项研究中，我们使用激光诱导的开角型青光眼（OAG）模型来评估骨髓细胞群的潜力和组织修复的机制。此外，我们研究了激光诱导的组织重塑作为靶向效应细胞进入受损组织的方法。我们证明，在骨髓细胞，间充质干细胞（MSC）诱导小梁网再生。MSC注射到眼前房中导致比造血细胞更有效的眼内压（IOP）降低（p <0.001）和愈合。这种强大的效果归因于来自应激MSC的旁分泌因子，因为从暴露于低而非正常氧水平的MSC注射条件培养基导致IOP立即降低。此外，MSC及其分泌的因子诱导睫状体中发现的祖细胞池的再活化并增加细胞增殖。在室角内观察到增殖细胞至少1个月。激光诱导的重塑能够将MSC靶向受损区域，从而导致眼祖细胞的特异性增加。因此，我们的研究结果确定MSC及其分泌物作为OAG组织修复的关键介质，通过重新激活局部神经祖细胞。此外，激光治疗可能是一种有吸引力的策略，以促进MSC介导的祖细胞招募和慢性疾病的组织修复。
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.