Human Cartilage-Derived Progenitors Resist Terminal Differentiation and Require CXCR4 Activation to Successfully Bridge Meniscus Tissue Tears.
Stem Cells
; 37(1): 102-114, 2019 01.
Article
em En
| MEDLINE
| ID: mdl-30358021
ABSTRACT
Meniscus injuries are among the most common orthopedic injuries. Tears in the inner one-third of the meniscus heal poorly and present a significant clinical challenge. In this study, we hypothesized that progenitor cells from healthy human articular cartilage (chondroprogenitor cells [C-PCs]) may be more suitable than bone-marrow mesenchymal stem cells (BM-MSCs) to mediate bridging and reintegration of fibrocartilage tissue tears in meniscus. C-PCs were isolated from healthy human articular cartilage based on their expression of mesenchymal stem/progenitor marker activated leukocyte cell adhesion molecule (ALCAM) (CD166). Our findings revealed that healthy human C-PCs are CD166+, CD90+, CD54+, CD106- cells with multilineage differentiation potential, and elevated basal expression of chondrogenesis marker SOX-9. We show that, similar to BM-MSCs, C-PCs are responsive to the chemokine stromal cell-derived factor-1 (SDF-1) and they can successfully migrate to the area of meniscal tissue damage promoting collagen bridging across inner meniscal tears. In contrast to BM-MSCs, C-PCs maintained reduced expression of cellular hypertrophy marker collagen X in monolayer culture and in an explant organ culture model of meniscus repair. Treatment of C-PCs with SDF-1/CXCR4 pathway inhibitor AMD3100 disrupted cell localization to area of injury and prevented meniscus tissue bridging thereby indicating that the SDF-1/CXCR4 axis is an important mediator of this repair process. This study suggests that C-PCs from healthy human cartilage may potentially be a useful tool for fibrocartilage tissue repair/regeneration because they resist cellular hypertrophy and mobilize in response to chemokine signaling. Stem Cells 2019;37102-114.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Cartilagem Articular
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Receptores CXCR4
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Condrogênese
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Menisco
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article