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Editorial Commentary: Are We Ready to Apply Stem Cell Therapy in Rotator Cuff Tear Surgery?

      Abstract

      For rotator cuff tear surgery, application of mesenchymal stem cells (MSCs) is a promising new option. Among various MSC sources, synovial tissue contains a high number of MSCs with high chondrogenic potential. Because chondrogenic formation is an important factor in enthesis healing in rotator cuff repair, synovial MSCs derived from the subacromial bursa are superior candidates for the augmentation of rotator cuff tear surgery.
      Retear of the rotator cuff after repair remains a challenging issue. Several biological augmentation strategies, such as the application of growth factors
      • Yonemitsu R.
      • Tokunaga T.
      • Shukunami C.
      • et al.
      Fibroblast growth factor 2 enhances tendon-to-bone healing in a rat rotator cuff repair of chronic tears.
      • Yoon J.P.
      • Lee C.H.
      • Jung J.W.
      • et al.
      Sustained delivery of transforming growth factor beta1 by use of absorbable alginate scaffold enhances rotator cuff healing in a rabbit model.
      or platelet-rich plasma,
      • Saltzman B.M.
      • Jain A.
      • Campbell K.A.
      • et al.
      Does the use of platelet-rich plasma at the time of surgery improve clinical outcomes in arthroscopic rotator cuff repair when compared with control cohorts? A systematic review of meta-analyses.
      have been reported. Application of mesenchymal stem cells (MSCs) is one of the promising new options for rotator cuff tear surgery; several articles have shown the positive effects of this augmentation in animal and human studies.
      • Rothrauff B.B.
      • Smith C.A.
      • Ferrer G.A.
      • et al.
      The effect of adipose-derived stem cells on enthesis healing after repair of acute and chronic massive rotator cuff tears in rats.
      • Jo C.H.
      • Chai J.W.
      • Jeong E.C.
      • et al.
      Intratendinous injection of autologous adipose tissue-derived mesenchymal stem cells for the treatment of rotator cuff disease: A first-in-human trial.
      • Kim Y.S.
      • Sung C.H.
      • Chung S.H.
      • Kwak S.J.
      • Koh Y.G.
      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.
      • Dyrna F.
      • Zakko P.
      • Pauzenberger L.
      • McCarthy M.B.
      • Mazzocca A.D.
      • Dyment N.A.
      Human subacromial bursal cells display superior engraftment Versus bone marrow stromal cells in Murine tendon repair.
      All prior studies have used enzymatic digestion with collagenase to isolate MSCs. The current article “Comparison of Preparation Techniques for Isolating Subacromial Bursa-Derived Cells as a Potential Augment for Rotator Cuff Tear” reported by Morikawa, Muench, Baldino, Kia, Johnson, Otto, Pauzenberger, Dyrna, McCarthy, and Mazzocca
      • Morikawa Muench
      • Baldino Kia
      • Johnson Otto
      • et al.
      Comparison of preparation techniques for isolating subacromial bursa-derived cells as a potential augment for rotator cuff tear.
      revealed that a similar number of subacromial bursa–derived cells were obtained using a chopping technique to mechanically isolate cells as when using collagenase digestion. The chopping technique simplifies MSC preparation for rotator cuff repair.
      Among the potential sources of MSCs for rotator cuff tears, synovial tissue derived from the subacromial bursa appears to be the best. In our in vitro study, we showed that subacromial bursa–derived cells have properties of MSCs: specific cell surface markers, high proliferation potential, and multipotency.
      • Utsunomiya H.
      • Uchida S.
      • Sekiya I.
      • Sakai A.
      • Moridera K.
      • Nakamura T.
      Isolation and characterization of human mesenchymal stem cells derived from shoulder tissues involved in rotator cuff tears.
      Although the bone marrow is a representative MSC source, synovial MSCs are considered superior to bone marrow–derived MSCs because synovial MSCs have higher chondrogenic potential than bone marrow MSCs,
      • Sakaguchi Y.
      • Sekiya I.
      • Yagishita K.
      • Muneta T.
      Comparison of human stem cells derived from various mesenchymal tissues: Superiority of synovium as a cell source.
      and synovial tissue has considerably higher concentrations of MSCs than bone marrow.
      • Sakaguchi Y.
      • Sekiya I.
      • Yagishita K.
      • Muneta T.
      Comparison of human stem cells derived from various mesenchymal tissues: Superiority of synovium as a cell source.
      • Nimura A.
      • Muneta T.
      • Koga H.
      • et al.
      Increased proliferation of human synovial mesenchymal stem cells with autologous human serum: Comparisons with bone marrow mesenchymal stem cells and with fetal bovine serum.
      In the current article, Morikawa et al.
      • Morikawa Muench
      • Baldino Kia
      • Johnson Otto
      • et al.
      Comparison of preparation techniques for isolating subacromial bursa-derived cells as a potential augment for rotator cuff tear.
      collected 200 mg of the subacromial bursa. We previously showed that 1 mg of the subacromial bursa contained approximately 1.1 million nucleated cells. Of these nucleated cells, up to 1.6% had a fraction of MSCs.
      • Utsunomiya H.
      • Uchida S.
      • Sekiya I.
      • Sakai A.
      • Moridera K.
      • Nakamura T.
      Isolation and characterization of human mesenchymal stem cells derived from shoulder tissues involved in rotator cuff tears.
      This means that 3.5 million MSCs are included in 200 mg of the subacromial bursa without any expansion process. If surgeons need 3.5 million bone marrow–derived MSCs, they require more than 150 mL of bone marrow.
      • Sakaguchi Y.
      • Sekiya I.
      • Yagishita K.
      • Muneta T.
      Comparison of human stem cells derived from various mesenchymal tissues: Superiority of synovium as a cell source.
      • Nimura A.
      • Muneta T.
      • Koga H.
      • et al.
      Increased proliferation of human synovial mesenchymal stem cells with autologous human serum: Comparisons with bone marrow mesenchymal stem cells and with fetal bovine serum.
      The subacromial bursa is a “waste tissue” during shoulder surgery, and 200 mg of the subacromial bursa is very easy to harvest.
      • Utsunomiya H.
      • Uchida S.
      • Sekiya I.
      • Sakai A.
      • Moridera K.
      • Nakamura T.
      Isolation and characterization of human mesenchymal stem cells derived from shoulder tissues involved in rotator cuff tears.
      The normal tendon-bone junction of the rotator cuff and humeral head is a cartilage tissue called the “enthesis.”
      • Benjamin M.
      • Moriggl B.
      • Brenner E.
      • Emery P.
      • McGonagle D.
      • Redman S.
      The “enthesis organ” concept: Why enthesopathies may not present as focal insertional disorders.
      However, rotator cuff tear surgery results in direct tendon-bone healing without cartilage formation.
      • Galatz L.M.
      • Sandell L.J.
      • Rothermich S.Y.
      • et al.
      Characteristics of the rat supraspinatus tendon during tendon-to-bone healing after acute injury.
      The elasticity of the tendon-bone junction can be one of the factors determining tissue strength.
      • Su W.
      • Li X.
      • Zhao S.
      • et al.
      Native enthesis preservation versus removal in rotator cuff repair in a rabbit model.
      As tendon-bone healing with cartilage formation will improve the clinical outcome of rotator cuff tear surgery, synovial MSCs derived from the subacromial bursa are superior candidates for augmentation in rotator cuff tear surgery. We are very close to initiating MSC therapy for patients with rotator cuff tears in the clinical setting.

      Supplementary Data

      References

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        Sustained delivery of transforming growth factor beta1 by use of absorbable alginate scaffold enhances rotator cuff healing in a rabbit model.
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