Cell-based therapy in soft tissue sports injuries of the knee: a systematic review

ABSTRACT

Introduction

An ever-increasing number of clinics are offering purportedly ‘regenerative’ stem-cell treatments, although cell-based therapies may not primarily act as stem cells and have shown the ability to regenerate end-target tissues in some clinical studies only. We aim to systematically review the evidence for their use in soft-tissue sports injuries of the knee.

Areas covered

A search for articles pertaining to the use of preparations of, or containing, mesenchymal stem cells (MSCs) in human subjects in sports knee injuries yielded 14 relevant results for inclusion after screening: 7 used cultured MSCs, 5 bone marrow concentrate (BMC), and the remaining 2 evaluated stromal vascular fraction (SVF) and tenocyte-like-cells. Most studies were level 3 or lower (n = 9).

Expert opinion

There is insufficient high-quality evidence for the use of cell-based therapies that demonstrates either ligamentous or tendinous healing, meniscal volume restoration, or post-traumatic osteoarthritis amelioration/regression. Methods of cell harvesting, preparation, and application are highly heterogenous. Efforts should be directed toward standardization of protocols and their reporting, starting with more basic scientific investigations of MSCs and their niche, as well as rigorous, large clinical RCTs adhering to the reporting principles set out by recent expert consensus.

KEYWORDS:

• Cell-based therapy
• mesenchymal stem cell
• anterior cruciate ligament injury
• patellar tendinopathy
• meniscal tear

Article Highlights

• Of 14 eligible articles investigating cell-based therapies in sports injuries of the knee most studies were level 3 or lower (n=9), few were level 1 (n=2) or level 2 (n=3)

• The included level 1 and 2 studies evidenced no statistically significant difference in imaging outcomes evaluating ligamentous or tendinous healing, meniscal volumes, or post-traumatic osteoarthritis at final follow up.

• The included level 3 or below studies all showed positive imaging findings, but the only one of these studies which compared the treatment group to a control retrospectively showed no statistically significant inter-group difference.

• The harvesting techniques, preparation, and application of cell-based therapies are highly heterogenous. The protocols used and their reporting must be standardized.

• Areas that require further exploration and research include: simulating the stem cell ‘niche,’ preconditioning MSCs in vitro, and elucidating the effect of source donor variability on cell-based therapy efficacy.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.