Perivascular-Derived Stem Cells with Neural Crest Characteristics Are Involved in Tendon Repair

Xu, Wei; Sun, Yanjun; Zhang, Jinye; Xu, Kang; Pan, Lianhong; He, Long; Song, Yang; Njunge, Lucy Wanjiru; Xu, Zhiling; Chiang, Martin Y.; Sung, Kuo‐Li Paul; Chuong, Cheng Ming; Yang, Li

doi:10.1089/scd.2014.0036

Cited by 27 publications

(32 citation statements)

References 34 publications

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“…Stem/progenitor cells derived from torn human rotator cuff tendons were characterized and determined to be multipotent MSCs with the ability to undergo multilineage differentiation . Vascularized peritenon, the loose connective tissue surrounding the tendon, harbors a unique population of stem/progenitor cells that expressed markers consistent with neural crest stem cells (NCSCs), such as P75 + (p75 neurotrophin receptor) . In response to tendon injury in a window defect model in the rat patellar tendon, P75 + cells, originating from the neural crest, increased in number and detached from vessels upon tendon injury, migrated to the interstitial space, and may contribute to the deposition of extracellular matrix (ECM) .…”

Section: Tendon Stem/progenitor Cellsmentioning

confidence: 99%

“…47 In response to tendon injury in a window defect model in the rat patellar tendon, P75 + cells, originating from the neural crest, increased in number and detached from vessels upon tendon injury, migrated to the interstitial space, and may contribute to the deposition of extracellular matrix (ECM). 47 In a rat model of Achilles rupture, stem/progenitor cells infiltrated the entire length of the Achilles tendon at 1 and 2 weeks post-rupture. 48 However, octamer-binding transcription factor 3/4 (Oct 3/4) + cells mainly localized to the injury site, while the number of nucleostemin (Nst) + cells generally increased throughout the tendon, suggesting that distinct populations of stem cells may serve different reparative functions.…”

Section: Tendon Stem/progenitor Cellsmentioning

confidence: 99%

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Mesenchymal stem cells in tendon repair and regeneration: basic understanding and translational challenges

Leong

Sun

2016

Annals of the New York Academy of Sciences

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Tendon injuries are common and present a clinical challenge because they often respond poorly to treatment and require prolonged rehabilitation. Current treatments often do not completely repair or regenerate the injured or diseased tendon to its native composition, structure, and mechanical properties. Stem cell-based therapies have brought new hope for tissue repair and regeneration, including that for tendon rupture and tendinopathy. Despite tremendous effort and progress, the success of stem cell-based studies on tendon repair and regeneration has mainly been limited to preclinical studies with few clinical applications. In this concise review, we discuss basic understanding and translational challenges of using mesenchymal stem cells (MSCs) for tendon repair and regeneration, with a focus on (1) tendon stem/progenitor cells (TSPCs) and therapeutic approaches using TSPCs and other MSCs, (2) regulation of fate determination in MSCs for tendon-lineage differentiation, (3) pretreatment and condition of stem/progenitor cells for transplantation, and (4) a treatment approach that involves stimulating endogenous stem cells to enhance tendon healing. The review concludes with discussion on future directions.

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Section: Tendon Stem/progenitor Cellsmentioning

confidence: 99%

Section: Tendon Stem/progenitor Cellsmentioning

confidence: 99%

Mesenchymal stem cells in tendon repair and regeneration: basic understanding and translational challenges

Leong

Sun

2016

Annals of the New York Academy of Sciences

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“…Previously we identified a subgroup of P75 + cells bearing NC characteristics that participate in tendon regeneration . However, we did not locate any NC cells with immune‐staining in the healthy tendon tissues, and it's still unknown where these cells came from.…”

Section: Discussionmentioning

confidence: 78%

Neural crest‐derived cells migrate from nerve to participate in Achilles tendon remodeling

Pan

Qiu

et al. 2018

Wound Repair Regeneration

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During tendon injury, nerve ingrowth is one of the earliest events of tendon repair and remodeling. Since peripheral neurons and associated cells are mostly derived from neural crest (NC) cells, we sought to investigate the role of NC-derived cells in tendon regeneration. Thus, we used Sox10-Cre/ROSA26-Flox-Red Fluorescent Protein (RFP) transgenic mice to trace these cells during tendon regeneration. After 4 weeks of Achilles tendon rupture, the injured tendon tissues were harvested for immunohistological analyses, cell isolation, and phenotype identification. In addition, the tenocytes were co-cultured with RFP labeled cells to examine cellular functions. Following the injury, a significant number of RFP-labeled cells penetrated into the wound site and reached a peak (∼30% of cells) after 2 weeks, and then stabilized at a level of approximately 20%. Interestingly, 36.9% RFP labeled cells in the injured area expressed Tuj1, suggesting that most of the cells are peripheral neurons. Some RFP /Tuj1 cells were also found adjacent to newly formed blood vessels in the tendon. Importantly, the existing neuropeptide Y (NPY) and neuropeptide Y receptor (NPYr) in the invading nerve and blood vessels were directly correlated. In addition, there were also RFP cells (∼30%) negative for neuronal markers but positive for fibroblast markers, that is, FAP (34.7%) and Vimentin (Vmt) (27.2%), and approximately 10% positive for Sox10. Indeed, many RFP cells isolated from the ruptured Achilles tendon showed long spindle shapes and expressed fibroblast phenotypic markers FSP1 and FAP. Part of the Sox10 RFP-labeled cells exhibited osteogenic and adipogenic differentiation ability. It is concluded that after Achilles tendon injury, nerves sprout into the wound site. The NC-derived Vmt /FAP mesenchymal cells and peripheral nerves participate in tendon regeneration.

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“…Quantitative real‐time polymerase chain reaction (PCR) was performed with the SsoAdvanced SYBR Green PCR supermix (1725264, Bio‐Rad) using iCycler (Bio‐Rad) according to described techniques (Xu et al, ). Total RNA was isolated from the collected cells using a MagMAX™‐96 Viral RNA Isolation Kit (AMB18365, Thermo Fisher) and then reverse transcribed into complementary DNA (cDNA) with a high‐capacity cDNA reverse transcription kit (4368813, Thermo Fisher) according to the manufacturer's protocol.…”

Section: Methodsmentioning

confidence: 99%

The use of mechano growth factor to prevent cartilage degeneration in knee osteoarthritis

Song

et al. 2017

J Tissue Eng Regen Med

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Previous studies have attached more importance to growth factors in treating cartilage degeneration and osteoarthritis (OA). Here, the capability of mechano growth factor-C24E (MGF) to prevent osteoarthritic cartilage degeneration was evaluated in vitro and in vivo. Using in vitro cultured human OA chondrocytes treated with 10-60-ng/ml MGF for 12 hr, we detected the cell proliferation, migration, and anabolism of OA chondrocytes. The unfolded protein response and the protein characteristic of OA pathology, such as transforming growth factor β, SMAD family member 3, and hypoxia-inducible factor 2α of OA chondrocytes, were also detected by western blotting. Furthermore, protein kinase RNA-like endoplasmic reticulum kinase was knocked down via small interfering RNA to illuminate the potential mechanism of MGF's treatment of OA. In a rabbit knee joint OA model, cartilage degeneration was inhibited after 2 weeks of treatment with 0.1-10-μg/ml MGF. This study demonstrated that MGF treatment can inhibit the pathological apoptosis of OA chondrocytes and promote the proliferation, migration, and matrix synthesis of the chondrocytes. The results also demonstrate that the degeneration of OA cartilage can be delayed by MGF treatment partially via unfolded protein response regulated by protein kinase RNA-like endoplasmic reticulum kinase and suggest a potential therapeutic application of MGF for OA treatment.

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Perivascular-Derived Stem Cells with Neural Crest Characteristics Are Involved in Tendon Repair

Cited by 27 publications

References 34 publications

Mesenchymal stem cells in tendon repair and regeneration: basic understanding and translational challenges

Mesenchymal stem cells in tendon repair and regeneration: basic understanding and translational challenges

Neural crest‐derived cells migrate from nerve to participate in Achilles tendon remodeling

The use of mechano growth factor to prevent cartilage degeneration in knee osteoarthritis

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