The protection of MSCs from apoptosis in nerve regeneration by TGFβ1 through reducing inflammation and promoting VEGF-dependent angiogenesis
| Autor: | Yongjie Zhang, Ziqiang Zhang, Yan Jin, Hailang Luo |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Vascular Endothelial Growth Factor A
Angiogenesis Sus scrofa Biophysics Neovascularization Physiologic Apoptosis Bioengineering Inflammation Mice SCID Biology Mesenchymal Stem Cell Transplantation Immunomodulation Rats Sprague-Dawley Transforming Growth Factor beta1 Biomaterials Neovascularization Mice Dogs medicine Animals Myelin Sheath Tissue Scaffolds Regeneration (biology) Mesenchymal stem cell Immunity Mesenchymal Stem Cells Nerve injury Sciatic Nerve Nerve Regeneration Rats Cytoprotection Mechanics of Materials Immunology Ceramics and Composites Cancer research Collagen Sciatic nerve medicine.symptom |
| Zdroj: | Biomaterials. 33:4277-4287 |
| ISSN: | 0142-9612 |
| DOI: | 10.1016/j.biomaterials.2012.02.042 |
| Popis: | Our previous report demonstrated that autologous adipose-derived mesenchymal stem cells (ADSCs) combined with xenogeneic acellular nerve matrix (XANM) can support the regeneration of defective nerves. Although ADSCs had the potential to replace Schwann cells in engineered-tissue nerves, apoptosis easily obstructed the ability to treat serious nerve injury in the host, such as a >50-mm-long nerve defect. In the present study, we found that, in combination with transforming growth factor β1 (TGFβ1), an ADSCs-XANM graft was sufficient to support the regeneration of a 50-mm sciatic nerve defect, which was not achieved using an ADSCs-XANM graft alone. Based on this finding, we further investigated how TGFβ1 coordinated with ADSCs to enhance nerve regeneration. In vitro, cell culture experiments demonstrated that TGFβ1 did not have a direct effect on ADSC proliferation, apoptosis, the cell cycle, or neural differentiation. The expression of VEGF, however, was significantly increased in ADSCs cultured with TGFβ1. In vivo, fluorescence labeling experiments demonstrated that the survival of transplanted ADSCs inoculated with XANM-TGFβ1 was higher than with XANM. Further study showed that TGFβ1 was capable of impairing the host immune response that was trigged by transplanted XANM. Additionally, we discovered that XANM-ADSCs in immunodeficient mice had apoptosis rates similar to XANM-ADSCs-TGFβ1 over a short time course (7 days). Once we blocked VEGF with a neutralizing antibody, the protective effect of TGFβ1 was impaired over a long time course (28 days). These results suggested that TGFβ1 was capable of enhancing the regenerative capacity of an XANM-ADSCs graft, mainly by protecting transplanted ADSCs from apoptosis. This effect was achieved in part through decreasing inflammation and promoting VEGF-dependent angiogenesis. |
| Databáze: | OpenAIRE |
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