Journal
JOURNAL OF MOLECULAR NEUROSCIENCE
Volume 49, Issue 2, Pages 250-261Publisher
HUMANA PRESS INC
DOI: 10.1007/s12031-012-9917-z
Keywords
BM-MSCs; Diabetic retinopathy; NOD mice; Wnt/beta-catenin signaling; Differentiation
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Funding
- Natural Science Foundation of China [81172841]
- Natural Science Foundation of Jiangsu Colleges and Universities Grant [09KJB320010, 10KJB320012]
- Top Six Types of Talents'' Financial Assistance of Jiangsu Province Grant
- Jiangsu province's outstanding medical academaic leader program [LJ201136]
- Graduate Student Innovation of Science and Technology Projects in Jiangsu Province
- Nantong University [13025045]
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Recent studies have shown that mesenchymal stem cells (MSCs) are expected to become promising therapeutic agents for the treatment of diabetic retinopathy (DR); moreover, we previously demonstrated that bone marrow (BM)-MSCs from nonobese diabetic (NOD) mice (an ideal DR model) had abnormal migration and adhesion. So, we hypothesized that NOD-MSCs also have abnormal retinal neuron-like differentiation potential. MSCs were cultured with brain-derived neurotrophic factor, nerve growth factor, and basic fibroblast growth factor. Western blot analysis and immunofluorescence both showed that the level of retinal neuron-like markers, such as glial fibrillary acidic protein, neuron-specific nuclear protein, tyrosine hydroxylase, Thy-1, glutamine synthetase, and rhodopsin was lower in NOD-MSCs than in imprinting control region MSCs. Furthermore, we explored the precise mechanisms controlling this change in NOD-MSCs. The expression levels of some important member proteins in Wnt/beta-catenin signaling were determined and suggested the downregulation of Wnt/beta-catenin signaling with retinal neuron-like differentiation of NOD-MSCs. Incubation of NOD-MSCs in medium supplemented with human recombinant Wnt1 resulted in a significant upregulation of retinal neuron-like markers, and the effects of Wnt1 were dose-dependent. Taken together, our study indicated that the inhibition of Wnt/beta-catenin signaling in NOD-MSCs after induction could contribute to the abnormal retinal neuron-like differentiation. These data provide important preclinical references supporting the basis for further development of autologous MSC-based therapies for DR.
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