Special issue on rotator cuff biology and healing
Biologic approaches to enhance rotator cuff healing after injury

https://doi.org/10.1016/j.jse.2011.10.004Get rights and content

Background

Despite the advances in surgical procedures to repair the rotator cuff, there is a high incidence of failure. Biologic approaches, such as growth factor delivery and stem cell and gene therapy, are potential targets for optimization to improve the outcome of rotator cuff therapies and reduce rates of reinjury. This article outlines the current evidence for growth factor and stem cell therapy in tendon healing and the augmentation of rotator cuff repair.

Methods

Literature on the PubMed–National Center for Biotechnology Information database was searched using the keywords growth factor, factor, gene therapy, stem cell, mesenchymal, or bone marrow in combination with rotator cuff, supraspinatus, or infraspinatus. Articles that studied growth factors or stem cells alone in rotator cuff repair were selected. Only 3 records showed use of stem cells in rotator cuff repair; thus, we expanded our search to include selected studies on stem cells and Achilles or patellar tendon repairs. Bibliographies and proceedings of meetings were searched to include additional applicable studies. We also included hitherto unpublished data by our group on the use of stem cell transplantation for rotator cuff therapy.

Results

More than 70 articles are summarized, with focus on recent original research papers and significant reviews that summarized earlier records.

Conclusions

Use of growth factors, stem cell therapy, and other tissue-engineering means serve to augment classical surgical rotator cuff repair procedures. The combination of stem cells and growth factors resulted in enhanced repair that emulated uninjured tissue, but the literature search reflected paucity of research in this field. Preclinical evidence from gene therapy and stem cell studies can be used as a start to move therapy from the experimental phase to clinical translation in patients.

Level of evidence

Review Article.

Section snippets

Methods

We used the PubMed and Google Scholar search engines to search the literature using the following search terms: growth factor, factor, gene therapy, stem cell, mesenchymal, or bone marrow combined with rotator cuff, supraspinatus, or infraspinatus, and included all permutations. We selected the papers that studied growth factors or stem cells alone in RC repair. Only 3 reports were found that used stem cells in RC therapy, and we thus expanded our stem cell search to include selected studies on

Growth factors

Numerous growth factors, including the bone morphogenetic proteins (BMPs), basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF), and transforming growth factor-β (TGF-β), can be found in the RC in predictable expression patterns during the early healing process. Many of these growth factors have a unique temporal expression profile and are thought to play an important role in directing tissue formation during the acute phase of RC healing.29, 60 Therefore, the ability of

Stem cell augmentation of tendon healing and RC repair

In this section, literature records on the use of stem cells for RC repair are reviewed, and significant findings are listed for each population. It is worth mentioning that tendon-derived stem/progenitor cells (TSPCs) have been isolated and cultured from human, mouse, rabbit, and rat tendons.3, 49, 50, 63 Data obtained thus far has shown that TSPCs can differentiate, form tendon-like tissue, and have the ability to synthesize tendon extracellular matrix. However, no studies using TSPCs to

Discussion

Augmentation of RC repair by growth factors and stem cells is intended to enhance the repair process, improve the mechanical force of the tendon, and reduce the rates of rerupture. This review has focused on research that investigated the influence of individual growth factors or stem cells from a single source to augment tendon healing and RC repair. Overall, data presented by several investigators indicate only a modest improvement in structure and biomechanics of tendon in RC repair after

Conclusions

Few studies exist documenting the role of stem cells, MDSCs in particular, in tendon tissue engineering; however, our laboratory has previously shown that the injection of MDSCs into the supraspinatus tendon of athymic rats resulted in the engraftment of transplanted cells into a continuous, longitudinal pattern, with a morphology comparable to resident tendon fibers.44 The ability of MDSCs to improve tendon healing has not been fully demonstrated thus far and remains a goal of future studies,

Acknowledgment

The authors are grateful to Aaron Boyer for technical help.

Disclaimer

Funds used in the preparation of this manuscript were provided by the Henry Mankin Endowed Chair at the University of Pittsburgh to Johnny Huard. Some of the data included were obtained through research funded by a Orthopaedic Research Education Foundation (OREF) grant to Vonda J. Wright.

Johnny Huard receives remuneration as a consultant and also receives royalties from Cook MyoSite, Inc, Pittsburgh, PA, USA. None of the other authors, their immediate families, and any research foundations with

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