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Tendon stem progenitor cells: Understanding the biology to inform therapeutic strategies for tendon repair.

ABSTRACT: Tendon and ligament injuries are a leading cause of healthcare visits with significant impact in terms of economic cost and reduced quality of life. To date, reparative strategies remain largely restricted to conservative treatment or surgical repair. However, these therapies fail to restore native tendon structure and function; thus, the tissue may re-rupture or degenerate with time. To improve tendon healing, one promising strategy may be harnessing the innate potential of resident tendon stem/progenitor cells (TSPCs) to guide tenogenic regeneration. In this review, we outline recent advances in the identification and characterization of putative TSPC populations, and discuss biochemical, biomechanical, and biomaterial methods employed for their culture and differentiation. Finally, we identify limitations in our current understanding of TSPC biology, key challenges for their use, and potential therapeutic strategies to inform cell-based tendon repair. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1270-1280, 2019.

SUBMITTER: Walia B

PROVIDER: S-EPMC6823601 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Tendon stem progenitor cells: Understanding the biology to inform therapeutic strategies for tendon repair.

Walia Bhavita B Huang Alice H AH

Journal of orthopaedic research : official publication of the Orthopaedic Research Society 20181018 6

Tendon and ligament injuries are a leading cause of healthcare visits with significant impact in terms of economic cost and reduced quality of life. To date, reparative strategies remain largely restricted to conservative treatment or surgical repair. However, these therapies fail to restore native tendon structure and function; thus, the tissue may re-rupture or degenerate with time. To improve tendon healing, one promising strategy may be harnessing the innate potential of resident tendon stem ...[more]

PMID: 30270569

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Project description:BACKGROUND:Tendon stem/progenitor cells (TSPC) exhibit a low proliferative response to heal tendon injury, leading to limited regeneration outcomes. Exogenous growth factors that activate TSPC proliferation have emerged as a promising approach for treatment. Here, we evaluated the pigment epithelial-derived factor (PEDF)-derived short peptide (PSP; 29-mer) for treating acute tendon injury and to determine the timing and anatomical features of CD146- and necleostemin-positive TSPC in the tendon healing process. METHODS:Tendon cells were isolated from rabbit Achilles tendons, stimulated by the 29-mer and analyzed for colony-forming capacity. The expression of the TSPC markers CD146, Oct4, and nestin, induced by the 29-mer, was examined by immunostaining and western blotting. Tendo-Achilles injury was induced in rats by full-thickness insertion of an 18-G needle and immediately treated topically with an alginate gel, loaded with 29-mer. The distribution of TSPC in the injured tendon and their proliferation were monitored using immunohistochemistry with antibodies to CD146 and nucleostemin and by BrdU labeling. RESULTS:TSPC markers were enriched among the primary tendon cells when stimulated by the 29-mer. The 29-mer also induced the clonogenicity of CD146+ TSPC, implying TSPC stemness was retained during TSPC expansion in culture. Correspondingly, the expanded TSPC differentiated readily into tenocyte-like cells after removal of the 29-mer from culture. 29-mer/alginate gel treatment caused extensive expansion of CD146+ TSPC in their niche on postoperative day 2, followed by infiltration of CD146+/BrdU- TSPC into the injured tendon on day 7. The nucleostemin+ TSPC were located predominantly in the healing region of the injured tendon in the later phase (day 7) and exhibited proliferative capacity. By 3?weeks, 29-mer-treated tendons showed more organized collagen fiber regeneration and higher tensile strength than control tendons. In culture, the mitogenic effect of the 29-mer was found to be mediated by the phosphorylation of ERK2 and STAT3 in nucleostemin+ TSPC. CONCLUSIONS:The anatomical analysis of TSPC populations in the wound healing process supports the hypothesis that substantial expansion of resident TSPC by exogenous growth factor is beneficial for tendon healing. The study suggests that synthetic 29-mer peptide may be an innovative therapy for acute tendon rupture.

Dataset Information

Tendon stem progenitor cells: Understanding the biology to inform therapeutic strategies for tendon repair.

Publications

Tendon stem progenitor cells: Understanding the biology to inform therapeutic strategies for tendon repair.

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