Harnessing endogenous stem/progenitor cells for tendon regeneration
| Autor: | Yena Jun, Chang H. Lee, Solaiman Tarafder, Kristy Kao, Jeremy J. Mao, Francis Y. Lee, G. W. Yang |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
MAP Kinase Signaling System
Cellular differentiation CD146 Antigen Biology Stem cell marker Colony-Forming Units Assay Rats Sprague-Dawley Tendons Tendon Injuries Animals Regeneration Progenitor cell Cell Proliferation Wound Healing Tissue Engineering Regeneration (biology) Multipotent Stem Cells Connective Tissue Growth Factor Cell Differentiation General Medicine Cell biology Rats Endothelial stem cell Adult Stem Cells Multipotent Stem Cell Focal Adhesion Kinase 1 Immunology Stem cell Adult stem cell Research Article |
| Popis: | Current stem cell-based strategies for tissue regeneration involve ex vivo manipulation of these cells to confer features of the desired progenitor population. Recently, the concept that endogenous stem/progenitor cells could be used for regenerating tissues has emerged as a promising approach that potentially overcomes the obstacles related to cell transplantation. Here we applied this strategy for the regeneration of injured tendons in a rat model. First, we identified a rare fraction of tendon cells that was positive for the known tendon stem cell marker CD146 and exhibited clonogenic capacity, as well as multilineage differentiation ability. These tendon-resident CD146+ stem/progenitor cells were selectively enriched by connective tissue growth factor delivery (CTGF delivery) in the early phase of tendon healing, followed by tenogenic differentiation in the later phase. The time-controlled proliferation and differentiation of CD146+ stem/progenitor cells by CTGF delivery successfully led to tendon regeneration with densely aligned collagen fibers, normal level of cellularity, and functional restoration. Using siRNA knockdown to evaluate factors involved in tendon generation, we demonstrated that the FAK/ERK1/2 signaling pathway regulates CTGF-induced proliferation and differentiation of CD146+ stem/progenitor cells. Together, our findings support the use of endogenous stem/progenitor cells as a strategy for tendon regeneration without cell transplantation and suggest this approach warrants exploration in other tissues. |
| Databáze: | OpenAIRE |
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