Human Cartilage-Derived Progenitors Resist Terminal Differentiation and Require CXCR4 Activation to Successfully Bridge Meniscus Tissue Tears.

dc.contributor.author

Jayasuriya, Chathuraka T

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Twomey-Kozak, John

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Newberry, Jake

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Desai, Salomi

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Feltman, Peter

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Franco, Jonathan R

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Li, Neill

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Terek, Richard

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Ehrlich, Michael G

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Owens, Brett D

dc.date.accessioned

2022-10-06T17:37:26Z

dc.date.available

2022-10-06T17:37:26Z

dc.date.issued

2019-01

dc.date.updated

2022-10-06T17:37:10Z

dc.description.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;37:102-114.

dc.identifier.issn

1066-5099

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1549-4918

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https://hdl.handle.net/10161/26069

dc.language

eng

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Oxford University Press (OUP)

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Stem cells (Dayton, Ohio)

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10.1002/stem.2923

dc.subject

Cartilage, Articular

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Animals

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Humans

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Rats

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Receptors, CXCR4

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Cell Differentiation

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Chondrogenesis

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Meniscus

dc.title

Human Cartilage-Derived Progenitors Resist Terminal Differentiation and Require CXCR4 Activation to Successfully Bridge Meniscus Tissue Tears.

dc.type

Journal article

duke.contributor.orcid

Li, Neill|0000-0001-9149-4859

pubs.begin-page

102

pubs.end-page

114

pubs.issue

1

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Duke

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School of Medicine

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Clinical Science Departments

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Orthopaedic Surgery

pubs.publication-status

Published

pubs.volume

37

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