Effects of lubricant and autologous bone marrow stromal cell augmentation on immobilized flexor tendon repairs

Zhao, Chunfeng; Ozasa, Yasuhiro; Shimura, Haruhiko; Reisdorf, Ramona L.; Thoreson, Andrew R.; Jay, Gregory D.; Moran, Steven L.; An, Kai Nan; Amadio, Peter C.

doi:10.1002/jor.22980

Cited by 20 publications

(29 citation statements)

References 46 publications

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“…MSCs are multipotent stem cells with significant potential in the field of regenerative medicine. Numbers of previous studies have demonstrated beneficial effects of BMSCs implantation in improving tendon healing after injury . Pacini et al used suspension of undifferentiated BMSCs for equine superficial digital flexor tendon repair and reported improved outcome .…”

Section: Discussionmentioning

confidence: 99%

“…MSCs have been successfully identified and isolated from a variety of tissues including adipose tissue, umbilical cord, bone marrow, amniotic fluid, skeletal muscle, and cartilage, among which bone marrow‐derived MSCs (BMSCs) is most commonly used for tissue regeneration and cell therapy because of their easy accessibility and expandability . Recently, regenerative approaches incorporating BMSCs delivery have been explored using in vivo or ex vivo model, with promising evidences showing promoted flexor tendon repair and healing . Concomitantly, BMSCs have been isolated from several experimental animals for the growing interest and needs of utilizing cell‐based therapies .…”

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Isolation and characterization of turkey bone marrow‐derived mesenchymal stem cells

Liu

Zhu

et al. 2019

Journal Orthopaedic Research

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Flexor tendon injury is often associated with suboptimal outcomes and results in substantial digit dysfunction. Stem cells have been isolated from several experimental animals for the growing interest and needs of utilizing cell‐based therapies. Recently, turkey has been developed as a new large animal model for flexor tendon research. In the present study, we reported the isolation and characterization of bone marrow‐derived mesenchymal stem cells (BMSCs) from 8‐ to 12‐month‐old heritage‐breed turkeys. The isolated cells demonstrated fibroblast‐like morphology, clonogenic capacity, and high proliferation rate. These cells were positive for surface antigens CD90, CD105, and CD44, but were negative for CD45. The multipotency of turkey BMSCs was determined by differentiating cells into osteogenic, adipogenic, chondrogenic, and tenogenic lineages. There was upregulated gene expression of tenogenic markers, including mohawk, tenomodulin, and EGR1 as well as increased collagen synthesis in BMP12 induced cells. The successful isolation and verification of bone marrow‐derived MSCs from turkey would provide opportunities of studying cell‐based therapies and developing new treatments for tendon injuries using this novel preclinical large animal model. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1419–1428, 2019.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Isolation and characterization of turkey bone marrow‐derived mesenchymal stem cells

Liu

Zhu

et al. 2019

Journal Orthopaedic Research

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“…10,16 More than 80% of the dry weight of a tendon is composed of COL1 and COL3. 17 Production of COL1 and COL3 indicates the cell tenogenic phenotype and activity. 10 Our study showed that mechanical stimulation with seeded BMSCs upregulated COL1 expression more than 30-fold and COL3 expression more than ten-fold compared with BMSC treatments.…”

Section: Discussionmentioning

confidence: 99%

The revitalisation of flexor tendon allografts with bone marrow stromal cells and mechanical stimulation

Thoreson

Gingery

et al. 2017

Bone & Joint Research

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ObjectivesThe present study describes a novel technique for revitalising allogenic intrasynovial tendons by combining cell-based therapy and mechanical stimulation in an ex vivo canine model.MethodsSpecifically, canine flexor digitorum profundus tendons were used for this study and were divided into the following groups: (1) untreated, unprocessed normal tendon; (2) decellularised tendon; (3) bone marrow stromal cell (BMSC)-seeded tendon; and (4) BMSC-seeded and cyclically stretched tendon. Lateral slits were introduced on the tendon to facilitate cell seeding. Tendons from all four study groups were distracted by a servohydraulic testing machine. Tensile force and displacement data were continuously recorded at a sample rate of 20 Hz until 200 Newton of force was reached. Before testing, the cross-sectional dimensions of each tendon were measured with a digital caliper. Young’s modulus was calculated from the slope of the linear region of the stress-strain curve. The BMSCs were labeled for histological and cell viability evaluation on the decellularized tendon scaffold under a confocal microscope. Gene expression levels of selected extracellular matrix tendon growth factor genes were measured. Results were reported as mean ± SD and data was analyzed with one-way ANOVAs followed by Tukey’s post hoc multiple-comparison test.ResultsWe observed no significant difference in cross-sectional area or in Young’s modulus among the four study groups. In addition, histological sections showed that the BMSCs were aligned well and viable on the tendon slices after two-week culture in groups three and four. Expression levels of several extracellular matrix tendon growth factors, including collagen type I, collagen type III, and matrix metalloproteinase were significantly higher in group four than in group three (p < 0.05).ConclusionLateral slits introduced into de-cellularised tendon is a promising method of delivery of BMSCs without compromising cell viability and tendon mechanical properties. In addition, mechanical stimulation of a cell-seeded tendon can promote cell proliferation and enhance expression of collagen types I and III in vitro.Cite this article: J. H. Wu, A. R. Thoreson, A. Gingery, K. N. An, S. L. Moran, P. C. Amadio, C. Zhao. The revitalisation of flexor tendon allografts with bone marrow stromal cells and mechanical stimulation: An ex vivo model revitalising flexor tendon allografts. Bone Joint Res 2017;6:179–185. DOI: 10.1302/2046-3758.63.BJR-2016-0207.R1.

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“…This safe, targeted, sustained delivery approach represents a significant improvement compared to previous growth factor delivery strategies for tendon repair. 11,15,17 …”

Section: Discussionmentioning

confidence: 99%

Effect of connective tissue growth factor delivered via porous sutures on the proliferative stage of intrasynovial tendon repair

Linderman

Shen

Yoneda

et al. 2018

Journal Orthopaedic Research

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Recent growth factor, cell, and scaffold-based experimental interventions for intrasynovial flexor tendon repair have demonstrated therapeutic potential in rodent models. However, these approaches have not achieved consistent functional improvements in large animal trials due to deleterious inflammatory reactions to delivery materials and insufficient induction of targeted biological healing responses. In this study, we achieved porous suture-based sustained delivery of connective tissue growth factor (CTGF) into flexor tendons in a clinically relevant canine model. Repairs with CTGF-laden sutures were mechanically competent and did not show any evidence of adhesions or other negative inflammatory reactions based on histology, gene expression, or proteomics analyses at 14 days following repair. CTGF-laden sutures induced local cellular infiltration and a significant biological response immediately adjacent to the suture, including histological signs of angiogenesis and collagen deposition. There were no evident widespread biological effects throughout the tendon substance. There were significant differences in gene expression of the macrophage marker CD163 and anti-apoptotic factor BCL2L1; however, these differences were not corroborated by proteomics analysis. In summary, this study provided encouraging evidence of sustained delivery of biologically active CTGF from porous sutures without signs of a negative inflammatory reaction. With the development of a safe and effective method for generating a positive local biological response, future studies can explore additional methods for enhancing intrasynovial tendon repair. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2052-2063, 2018.

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Effects of lubricant and autologous bone marrow stromal cell augmentation on immobilized flexor tendon repairs

Cited by 20 publications

References 46 publications

Isolation and characterization of turkey bone marrow‐derived mesenchymal stem cells

Isolation and characterization of turkey bone marrow‐derived mesenchymal stem cells

The revitalisation of flexor tendon allografts with bone marrow stromal cells and mechanical stimulation

Effect of connective tissue growth factor delivered via porous sutures on the proliferative stage of intrasynovial tendon repair

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