Involvement of Indian hedgehog signaling in mesenchymal stem cell–augmented rotator cuff tendon repair in an athymic rat model

Zong, Jingfeng; Mosca, Michael J.; Degen, Ryan M.; Lebaschi, Amir; Carballo, Camila; Carbone, Andrew; Cong, Guang‐Ting; Liang, Ying; Deng, Xiang‐Hua; Rodeo, Scott A.

doi:10.1016/j.jse.2016.09.036

Cited by 23 publications

(22 citation statements)

References 31 publications

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“…Delivery of ASCs to augment rotator cuff repair in vivo generally reduces inflammation and the presence of inflammatory cells; however, functional properties do not improve . Similarly, delivery of bMSCs showed increased numbers of anti‐inflammatory M2 macrophages at later timepoints, in parallel with upregulated enthesis markers . Collectively, these studies indicate that MSCs derived from bone marrow or fat may have immunoprotective properties, but the impact on functional restoration may be minimal.…”

Section: Stem Cell‐based Therapies For Rotator Cuff Repairmentioning

confidence: 91%

“…Differentiation can be carried out in vitro to create an engineered tendon/enthesis construct prior to implantation, or naive MSCs can be delivered within a biomimetic matrix to promote the proper cell fate in situ . Commonly used scaffolds for rotator cuff include electrospun fibers, xenograft tendon scaffolds, or hydrogels (typically fibrin or type I collagen gels) . The use of a carrier vehicle is advantageous since it ensures proper localization of delivered cells; the environment provided by the scaffolds has the additional potential to improve host cell proliferation or differentiation.…”

Section: Stem Cell‐based Therapies For Rotator Cuff Repairmentioning

confidence: 99%

“…[116][117][118][119] Commonly used scaffolds for rotator cuff include electrospun fibers, xenograft tendon scaffolds, or hydrogels (typically fibrin or type I collagen gels). 43,59,[120][121][122][123] The use of a carrier vehicle is advantageous since it ensures proper localization of delivered cells; the environment provided by the scaffolds has the additional potential to improve host cell proliferation or differentiation. While MSCs delivered within such carriers generally showed some positive indicators of improved healing (such as improved histology, fibrocartilage deposition, or expression of enthesis markers), 46,120,122 functional outcomes have been mixed.…”

Section: Directed Differentiation Of Stem Cells In Vivomentioning

confidence: 99%

“…43,59,[120][121][122][123] The use of a carrier vehicle is advantageous since it ensures proper localization of delivered cells; the environment provided by the scaffolds has the additional potential to improve host cell proliferation or differentiation. While MSCs delivered within such carriers generally showed some positive indicators of improved healing (such as improved histology, fibrocartilage deposition, or expression of enthesis markers), 46,120,122 functional outcomes have been mixed. Although some studies reported improved mechanical properties, 120,123 others observed no differences relative to carrier or suture controls by the final timepoint.…”

Section: Directed Differentiation Of Stem Cells In Vivomentioning

confidence: 99%

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Biologics and stem cell‐based therapies for rotator cuff repair

Bianco

Moser

Galatz

et al. 2018

Annals of the New York Academy of Sciences

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The rotator cuff is composed of several distinct muscles and tendons that function in concert to coordinate shoulder motion. Injuries to these tendons frequently result in permanent dysfunction and persistent pain. Despite considerable advances in operation techniques, surgical repair alone still does not fully restore rotator cuff function. This review focuses on recent research in the use of biologics and stem cell-based therapies to augment repair, highlighting promising avenues for future work and remaining challenges. While a number of animal models are used for rotator cuff studies, the anatomy of the rotator cuff varies dramatically between species. Since the rodent rotator cuff shares the most anatomical features with the human, this review will focus primarily on rodent models to enable consistent interpretation of outcome measures.

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Section: Stem Cell‐based Therapies For Rotator Cuff Repairmentioning

confidence: 91%

Section: Stem Cell‐based Therapies For Rotator Cuff Repairmentioning

confidence: 99%

Section: Directed Differentiation Of Stem Cells In Vivomentioning

confidence: 99%

Section: Directed Differentiation Of Stem Cells In Vivomentioning

confidence: 99%

See 2 more Smart Citations

Biologics and stem cell‐based therapies for rotator cuff repair

Bianco

Moser

Galatz

et al. 2018

Annals of the New York Academy of Sciences

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“…The results showed improved fibrocartilage formation, collagen orientation, and biomechanical strength 2 weeks following repair 65 . Further analysis of the data demonstrate that Indian hedgehog (Ihh) and Sox9 signaling play an important role in the tendon-to-bone healing mechanism 66 .…”

Section: Current Cell-based Approachesmentioning

confidence: 99%

Cell-based Approaches for Augmentation of Tendon Repair

Carballo

Lebaschi

Rodeo

2017

Techniques in Shoulder &Amp; Elbow Surgery

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Cell-based approaches are among the principal interventions in orthobiologics to improve tendon and ligament healing and to combat degenerative processes. The number of options available for investigation are expanding rapidly and investigators have an increasing number of cell types to choose from for research purposes. However, in part due to the current regulatory environment, the list of available cells at clinicians’ disposal for therapeutic purposes is still rather limited. In this review, we present an overview of the main cellular categories in current use. Notable recent developments in cell-based approaches include the introduction of diverse sources of mesenchymal stem cells, pluripotent cells of extra-embryonic origin, and the emerging popularity of fully differentiated cells such as tenocytes and endothelial cells. Delivery strategies are discussed and a succinct discussion of the current regulatory environment in the United States is presented.

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Postoperative Tendon Loading With Treadmill Running Delays Tendon‐to‐Bone Healing: Immunohistochemical Evaluation in a Murine Rotator Cuff Repair Model

Wada

Lebaschi

Nakagawa

et al. 2019

Journal Orthopaedic Research

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Mechanical stress has an important effect on tendon-to-bone healing. The purpose of the present study was to compare tendon-to-bone healing in animals exposed to either tendon unloading (botulinum toxin injection) or excessive loading (treadmill running) in a murine rotator cuff repair model. Forty-eight C57BL/6 mice underwent unilateral supraspinatus tendon detachment and repair. Mice in the unloaded group were injected with botulinum toxin to the supraspinatus muscle. The contralateral shoulder of the unloaded group was used as a control. Mice were euthanized at 1, 2, and 4 weeks after surgery and evaluated with hematoxylin-eosin and immunohistochemical (IHC) staining for Ihh, Gli1, Wnt3a, and β-catenin. The positive staining area on IHC and the Modified Tendon Maturing Score were measured. The score of the unloaded group was significantly higher (better healing) than that of the treadmill group at 4 weeks. Ihh and the glioma-associated oncogene homolog 1 (Gli1) positive area in the unloaded group were significantly higher than those of the control group at 1 week. The peak time-points of the Ihh and Gli1 positive area was 1 week for the unloaded group and 2 weeks for the treadmill group. The Wnt3a positive area in the unloaded group was significantly higher than that of the control group at 2 weeks. The β-catenin positive area in the unloaded group was significantly higher than that of the treadmill group and the control group at 1 week. Our data indicated that the unloaded group has superior tendon maturation compared to the treadmill running group. Excessive tendon loading may delay the tendon healing process by affecting the activity of Ihh and Wnt/β-Catenin pathways.

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Involvement of Indian hedgehog signaling in mesenchymal stem cell–augmented rotator cuff tendon repair in an athymic rat model

Cited by 23 publications

References 31 publications

Biologics and stem cell‐based therapies for rotator cuff repair

Biologics and stem cell‐based therapies for rotator cuff repair

Cell-based Approaches for Augmentation of Tendon Repair

Postoperative Tendon Loading With Treadmill Running Delays Tendon‐to‐Bone Healing: Immunohistochemical Evaluation in a Murine Rotator Cuff Repair Model

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