Abstract
The use of stem cells in orthopaedics remains a controversial topic, stem cells remain experimental, and significant concerns exist. Studies evaluating diagnoses that may spontaneously resolve could be of low value absent a control group. Only same-day harvest of minimally manipulated stem cells is approved for use in the United States, and these minimally manipulated products may contain insufficient cells to affect outcomes. Extensively cultured cells do not qualify for use in the United States outside of an approved Investigational New Drug Application. Moreover, in other arenas, significant, serious adverse events have been reported after the use of manipulated stem cells. Both the US Food and Drug Administration and American Academy of Orthopaedic Surgeons have recognized the potential for abuse regarding this evolving technology. Published results using stems cells to treat rotator cuff disease are inconsistent, and the optimum source and preparation of the stem cells remains unknown.
I read with interest the article entitled “Intratendinous Injection of Mesenchymal Stem Cells for the Treatment of Rotator Cuff Disease: A 2-Year Follow-Up Study by Jo, Chai, Jeong, Oh, and Yoon.
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The authors studied patients aged 19 years and older with unilateral shoulder pain for more than 3 months of symptom duration, and were discovered to have a partial-thickness rotator cuff tear identified with ultrasonography or magnetic resonance imaging scans. The paper is to be commended in that the specific dose of stem cells was rigorously quantified. No control group was offered. The clinical response was generally dose dependent, with higher doses proving more efficacious. Night pain was not significantly improved at the lowest dose, and strength was not increased at final follow-up except at the highest dose.It has been more than half a decade since the seminal work of Hernigou et al.
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demonstrated outstanding results using stem cells to augment rotator cuff repairs, with 87% of tears augmented with stem cells remaining healed at 10-year follow-up versus only 44% without. Since then, published results using stem cells to treat rotator cuff disease have been far more inconsistent, and no study has been able to duplicate these outstanding results. Like the current paper, Kim et al.3
(not referenced by the authors) used adipose-derived stem cells to augment rotator cuff repair. This study was notable for its prospective, randomized design. Although structural outcomes favored the stem cell group, no improvement in clinical outcomes was noted. Other stem cell proponents have preferred bone marrow-derived cell,2
,4
and the optimum source and preparation of the stem cells remains controversial. Reviews of the use of stem cells in rotator cuff disease have generally been circumspect. Dickenson et al.5
in a recent 2019 review noted that “more human trials would need to look at these factors in similar time frames” and Mora et al.6
stated that “the use of stem cell therapy in rotator cuff should still be considered an experimental technique.”Currently, only same-day minimally manipulated stem cells are approved for use in the United States.
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These minimally manipulated products may contain insufficient stem cells to affect the outcome of any surgical procedure. The stem cells described in this paper in contrast are extensively cultured and would not qualify for use in the United States outside of an approved Investigational New Drug Application.US Food and Drug Administration
FDA warns about stem cell therapies.
FDA warns about stem cell therapies.
https://www.fda.gov/consumers/consumer-updates/fda-warns-about-stem-cell-therapies
Date accessed: January 7, 2020
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Although the authors report no adverse events in their study, significant, serious adverse events have been reported in the use of manipulated stem cells in other arenas.US Food and Drug Administration
FDA warns about stem cell therapies.
FDA warns about stem cell therapies.
https://www.fda.gov/consumers/consumer-updates/fda-warns-about-stem-cell-therapies
Date accessed: January 7, 2020
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Cost is also an issue. A single stem cell injection can range in price from $1,500 to $10,000 depending who does the injection, and these costs are currently entirely born by the patient.US Food and Drug Administration
FDA warns about stem cell therapies.
FDA warns about stem cell therapies.
https://www.fda.gov/consumers/consumer-updates/fda-warns-about-stem-cell-therapies
Date accessed: January 7, 2020
4
In summary, although further research continuing to search for the Holy Grail of rotator cuff management is critical, routine inclusion of stem cell products in rotator cuff injury is not yet ready for prime time. Both the US Food and Drug Administration
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and American Academy of Orthopaedic SurgeonsUS Food and Drug Administration
FDA warns about stem cell therapies.
FDA warns about stem cell therapies.
https://www.fda.gov/consumers/consumer-updates/fda-warns-about-stem-cell-therapies
Date accessed: January 7, 2020
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have recognized the potential for abuse regarding this evolving technology. The absence of a control group for a diagnosis that often sees spontaneous resolution is troublesome. Historically, at least dating back to Le Morte d'Arthur,9
searches for Holy Grails have been problematic and unsuccessful except for the most pure (shall we say researchers?). Rather than arbitrarily using (and charging for) stem cells in rotator cuff disease, high-quality, prospective, randomized studies will be required to enter the era of prime-time stem cell treatment of rotator cuff disease.Supplementary Data
- ICMJE author disclosure forms
References
- Intratendinous injection of mesenchymal stem cells for the treatment rotator cuff disease: a 2-year follow-up study.Arthroscopy. 2020; 36: 971-980
- Biologic augmentation of rotator cuff repair with mesenchymal stem cells during arthroscopy improves healing and prevents further tears: a case-controlled study.Int Orthop. 2014; 38: 1811-1818
- Does an injection of adipose-derived mesenchymal stem cells loaded in fibrin glue influence rotator cuff repair outcomes? A clinical and magnetic resonance imaging study.Am J Sports Med. 2017; 45: 2010-2018
- Controversy, cost may not dim potential of stem cells in the shoulder. Orthop Today.
- A critical review of regenerative therapies for shoulder rotator cuff injuries.SN Comprehensive Clin Med. 2019; 1: 205-214
- Stem cell therapy in the management of shoulder rotator cuff disorders.World J Stem Cells. 2015; 7: 691-699
- FDA warns about stem cell therapies.https://www.fda.gov/consumers/consumer-updates/fda-warns-about-stem-cell-therapiesDate accessed: January 7, 2020
- AAOS position statement use of emerging biologic therapies.
Malory T. Le Morte D’Arthur New York, NY: Penguin Books, 1969; volume II.
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Footnotes
The author reports no conflicts of interest in the authorship and publication of this article. Full ICMJE author disclosure forms are available for this article online, as supplementary material.
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