‘‘Stem Cell Treatments Flourish With Little Evidence That They Work’’

This was a headline in the May 13, 2019 New York Times. You must read the full article in this link.

Here is a nice review: The role of biologic agents in the management of common shoulder pathologies: current state and future directions
Here are their conclusions regarding platelet rich plasma (PRP). Given the wide variety of clinical results for PRP injections for various shoulder pathologies, expectations must be tempered by clinicians and patients. Although basic science literature supports a potential role in the management of rotator cuff tears, robust clinical data are lacking to support their widespread use.

Here are their conclusions regarding "stem cells" or "cell based therapy" or Bone marrow aspirate concentrate (BMAC). BMAC has the unique advantage of containing a very small population of mesenchymal stem cells and a high proportion of various growth factors, but its true clinical efficacy is still largely unknown. High-quality studies with appropriate control groups are needed to better define its clinical role. A critical deficiency in the current literature is the lack of information correlating the composition and/or biologic activity of marrow-derived cells and clinical outcomes. Furthermore, obtaining BMAC is an expensive procedure with unknown cost-effectiveness.

One of the key issues is the direct to consumer advertising of stem cell and related therapies See this link.

Comment: Currently we are seeing aggressive marketing and patient demand that has led to the indiscriminate use of cell therapy for a wide range of musculoskeletal conditions. It is of note that in many cases the high cost of these procedures is covered by the patient because insurance companies have not been convinced of their effectiveness. Because of the lack of data on their value to the patient, we avoid these interventions in our patients.

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Are PRP, stem cells, or biomaterials of value in rotator cuff repair?

Biologics for Rotator Cuff Repair A Critical Analysis Review

In their introduction, the authors state that "Despite an increase in the number of operations performed and enhanced surgical techniques, unacceptably high rates of failure of up to 94% still occur." They point out that this has driven intense scientific and commercial interest in "biologics" (platelet-rich plasma, stem cells, and biomaterials) as a possible means for enhancing the healing of attempted cuff repairs.

In their review, these authors note that

(1) among the many types of biologic augmentation, there is considerable heterogeneity of the content, quality, and quantity of growth factors used in platelet-rich plasma and bone marrow aspirate concentrate, and conclusions from individual studies may not necessarily be generalizable to other formulations within the group.

(2) current Level-I evidence suggests that universal use of platelet-rich plasma provides no significant clinical benefit in rotator cuff repair.
(3) although some evidence exists for the use of stem cells from bone marrow aspirate concentrate and the use of biologic grafts, results from Level-I studies are lacking and 

(4) level-I trials focused on the evaluation of clinical outcomes (i.e. using the Simple Shoulder Test, the American Shoulder and Elbow Surgeons score, the University of California at Los Angeles  shoulder score, or the Constant score) should be performed to help to determine the appropriate use of biologic augmentation in rotator cuff surgical procedures.

Comment: As these authors indicate, all of the scientific and commercial interest in biologics needs to be evaluated in terms of well controlled studies showing that clinical outcomes are better for patients receiving biologics in comparison to comparable patients not receiving them. These studies need to be carried out in recognition of the observation that over 10 million individuals are living with cuff tears and at most 4% of them get surgery each year. It is commonly observed that patients with cuff tears can respond to physical therapy. Furthermore, patients are commonly clinically improved after cuff repair surgery whether or not the surgery is successful in restoring the integrity of the cuff. From a clinical standpoint, therefore, biologics are going to need to make a big difference in order to justify their cost.

For a perspective on cuff repair as well as a Robert Frost poem, readers are invited to visit this post:

Rotator cuff repair - failure with continuity

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How you can support progress in shoulder surgery

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Are injections good for arthritis?

Injectable Biological Treatments for Osteoarthritis of the Knee

These authors reviewed the highly controversial topic of injectable biologic treatments for arthritis. 

Here are their conclusions:

 (1) platelet-rich plasma may provide symptomatic relief on a short-term basis, but long-term data are lacking on the effectiveness of PRP in changing the course of arthritis.

(2) stem cell therapy may provide symptomatic relief on a short-term basis, however it is unclear how to direct these cells to form useful new cartilage in an arthritic joint. 

See related post: Is there such a thing as injection arthropathy? which includes theAAOS recommendations on the use of injections.

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Stem cell therapy – what can be said about it?

Intra-ArticularCellular Therapy for Osteoarthritis and Focal Cartilage Defects of the Knee

Patients with shoulder arthritis and rotator cuff often ask, “I’ve heard about stem cell injections and cryopreserved, injectable amniotic fluid-derived allograft, would they help my shoulder?”

The authors of a recent systematic review of stem cell treatment of knee arthritis and articular cartilage defects concluded that “the efficacy of cellular therapy injections has not yet been established.

The value and effective use of cell therapy in orthopaedics remain unclear largely because of the absence of 

(1) rigorous blinded clinical trials, 

(2) standardized use of nomenclature to define cell populations, and 

(3) quantitative metrics to define cell populations and clinical and structural outcomes. 

Although many of the studies reported were randomized, patients had not been blinded. Because cellular therapy carries a high level of expectation for possible benefits, it can constitute a strong source of bias in enrollment and in perception of patient-reported outcome.” 

 While this article is about the knee, it is likely that even less quality information is available about the shoulder.

At present, we do not use these agents in our practice because the lack of evidence of their cost-effectiveness.

The effect of stem cells on chronic subscapularis tears - a rabbit model

Effect of the adipose-derived stem cell for the improvement of fatty degeneration and rotator cuff healing in rabbit model.

These authors sectioned the right and left subscapularis tendon at the insertion in 32 rabbits and wrapped the torn tendon with a 10-mm-long silicone Penrose drain with an 8-mm outer diameter to inhibit adhesion to the surrounding soft tissue. There four study groups: (1) repair + stem cells, (2) repair + saline, (3) stem cells without repair, and (4) saline without repair. Repair was carried out using two suture anchors. The adipose derived stem cells had been  previously cultured and were injected into the subscapularis muscle adjacent to the musculotendinous junction area. A fifth group of 8 rabbits served as normal controls. In each rabbit both shoulders were tested electromyographically, one side was additionally tested biomechanically and the other examined histologically.

At six weeks after surgery the animals were investigated.

The unprepared tendons (groups 3 and 4) did not heal.

On electromyographic evaluation, the stem cell +repair group exhibited a significantly larger compound muscle action potential area than the saline+repair group, achieving values  almost at the level of the control group.

The load-to-failure of the stem cell+repair group insignificantly higher than that of the saline+repair group.

The mean proportion of fatty infiltration in the subscapularis muscles was lower for the stem cell + repair group was lower than that of the other experimental groups. 

Comment: this is a nicely controlled animal study. Importantly, the authors investigated delayed repair in contrast to many prior studies that investigated only immediate repair after tendon sectioning. The authors were very forthcoming about he possible limitations of the study:

(1) most human cuff repairs are performed more than 6 weeks after the tear; chronic rotator cuff tears typically develop slowly over a long period of time. 

(2) the amount of fatty infiltration at the time of repair was not assessed.

(3) the histologic evaluation of tendon-to-bone healing was not evaluated.

(4) the level of fatty infiltration was only evaluated in a single section of muscle by histologic evaluation.

(5) muscle stimulation and contraction on EMG testing may not represent the functional aspects of the repaired muscle. 

(6) the injected stem cells were not tracked and the  molecular pathways involved in muscle regeneration were not explored.

Nevertheless, this study should stimulate investigation of the optimal dose, timing and longer term effects of stem cell injection prior to clinical application.

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To see the topics covered in this Blog, click here

Use the "Search" box to the right to find other topics of interest to you.

You may be interested in some of our most visited web pages including:shoulder arthritis, total shoulder, ream and run, reverse total shoulder, CTA arthroplasty, and rotator cuff surgery as well as the 'ream and run essentials'

See from which cities our patients come.

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Not much support for the use of biologics in rotator cuff repair.

Application of biologics in the treatment of the rotator cuff, meniscus, cartilage, and osteoarthritis.

Abstract: "Advances in our knowledge of cell signaling and biology have led to the development of products that may guide the healing/regenerative process. Therapies are emerging that involve growth factors, blood-derived products, marrow-derived products, and stem cells. Animal studies suggest that genetic modification of stem cells will be necessary; studies of cartilage and meniscus regeneration indicate that immature cells are effective and that scaffolds are not always necessary. Current preclinical animal and clinical human data and regulatory requirements are important to understand in light of public interest in these products."

With respect to rotator cuff repair, however, the authors conclude that 'synthesis of all the studies illustrates that there is no clear advantage to using PRP (platelet rich plasma) as a surgical adjunct to rotator cuff repair'. A similar statement was made about mesenchymal stem cells.

Comment: While there is no question that platelets, growth factors and stem cells are part of the body's response to injury and healing process, there are many complexities in trying to improve on nature's finely tuned healing response.

As pointed out the Rotator Cuff Tear Book, we consider rotator cuff repair when tendon of good quality can be brought to bone of good quality without undue tension on the repair. We then intentionally create a injury to the bone in the form of trough into which the tendon is secured. By creating this trough, we cause local bleeding and start the response to injury with the natural influx of platelets, growth factors, and stem cells.

More details on cuff repair technique are shown here.

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Consultation for those who live a distance away from Seattle.

Check out the new Shoulder Arthritis Book - click here.

Click here to see the new Rotator Cuff Book

To see the topics covered in this Blog, click here

Use the "Search" box to the right to find other topics of interest to you.

You may be interested in some of our most visited web pages including:shoulder arthritis, total shoulder, ream and run, reverse total shoulder, CTA arthroplasty, and rotator cuff surgery as well as the 'ream and run essentials'

See from which cities our patients come.

See the countries from which our readers come on this post.