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Mesenchymal Stem Cells Versus Fat Pad–Derived Cells

      To the Editor:
      We read the article “Mesenchymal Stem Cell Injections Improve Symptoms of Knee Osteoarthritis” in the April 2013 issue of your highly acclaimed journal with great interest.
      • Koh Y.-G.
      • Jo S.-B.
      • Kwon O.-R.
      • et al.
      Mesenchymal stem cell injections improve symptoms of knee osteoarthritis.
      We congratulate Koh et al. for their work, but we are very concerned about the erroneous use of the term “fat pad–derived mesenchymal stem cells (MSCs)” instead of “fat pad aspirate concentrate” or “fat pad–derived cells” (probably containing a small number of mesenchymal stem cells) in the article. It leads to serious confusion for the readers including ourselves.
      To use the term “fat pad–derived MSCs,” the cells should have been isolated from human adipose tissue by culture expansion and then characterized by the following: self-renewal, expression of specific cell surface markers, and multilineage differentiation. Thus the obtained cell population is relatively homogeneous,
      • Gimble J.M.
      • Bunnell B.A.
      • Chiu E.S.
      • Guilak F.
      Concise review: Adipose-derived stromal vascular fraction cells and stem cells: Let's not get lost in translation.
      which can be designated as “MSCs.” The other term, “fat pad aspirate concentrate” or “fat pad–derived cells,” means that the cell population is not isolated by culture expansion, so the cells are heterogeneous and may contain only a small number of MSCs.
      • Gimble J.M.
      • Bunnell B.A.
      • Chiu E.S.
      • Guilak F.
      Concise review: Adipose-derived stromal vascular fraction cells and stem cells: Let's not get lost in translation.
      In the introduction to the article, Koh et al.
      • Koh Y.-G.
      • Jo S.-B.
      • Kwon O.-R.
      • et al.
      Mesenchymal stem cell injections improve symptoms of knee osteoarthritis.
      state that “Buda et al. advocated the use of a one-step technique in repairing osteochondral lesions of the knee with bone marrow–derived mesenchymal stem cell transplantation.” However, the cells used in the study by Buda et al.
      • Buda R.
      • Vannini F.
      • Cavallo M.
      • Grigolo B.
      • Cenacchi A.
      • Giannini S.
      Osteochondral lesions of the knee: A new one-step repair technique with bone-marrow-derived cells.
      were not “MSCs” but were “bone marrow–derived cells” (in other words, “bone marrow aspirate concentrate”). It is clear that the title of the article only used the term “bone marrow–derived cells.” We believe that it is a serious error to interchange the term “bone marrow–derived cells” with “bone marrow–derived MSCs” because it is well known that both entities are different from each other, and this error adds more confusion to the already confusing information in terms of the clinical results of various types of cell therapies.
      Moreover, in the paragraph describing the surgical procedure and MSC harvesting technique, Koh et al.
      • Koh Y.-G.
      • Jo S.-B.
      • Kwon O.-R.
      • et al.
      Mesenchymal stem cell injections improve symptoms of knee osteoarthritis.
      described that “MSCs were derived and counted with a hemocytometer, as described previously.”
      • English A.
      • Jones E.A.
      • Corscadden D.
      • et al.
      A comparative assessment of cartilage and joint fat pad as a potential source of cells for autologous therapy development in knee osteoarthritis.
      • Wickham M.Q.
      • Erickson G.R.
      • Gimble J.M.
      • Vail T.P.
      • Guilak F.
      Multipotent stromal cells derived from the infrapatellar fat pad of the knee.
      However, in the referenced articles,
      • English A.
      • Jones E.A.
      • Corscadden D.
      • et al.
      A comparative assessment of cartilage and joint fat pad as a potential source of cells for autologous therapy development in knee osteoarthritis.
      • Wickham M.Q.
      • Erickson G.R.
      • Gimble J.M.
      • Vail T.P.
      • Guilak F.
      Multipotent stromal cells derived from the infrapatellar fat pad of the knee.
      cells from the infrapatellar fat pad were cultured and expanded in MSC expansion media. In this study cells from the infrapatellar fat pad were not cultured; thus the cell preparation took only 3 to 4 hours. Isolation of MSCs by culture expansion needs at least several days. Thus the authors' method for cell preparation was completely different from the previous method of MSC preparation in the referenced articles.
      • English A.
      • Jones E.A.
      • Corscadden D.
      • et al.
      A comparative assessment of cartilage and joint fat pad as a potential source of cells for autologous therapy development in knee osteoarthritis.
      • Wickham M.Q.
      • Erickson G.R.
      • Gimble J.M.
      • Vail T.P.
      • Guilak F.
      Multipotent stromal cells derived from the infrapatellar fat pad of the knee.
      This is a serious error in the description of the methods and citing of references.
      Although we acknowledge that this article is a leading clinical study using “fat pad–derived cells” in arthritic patients, we believe that it is very important to understand that the results of this study are not the results of using MSCs. We would like to ask the authors to change the erroneous term “mesenchymal stem cells” used in their article to an appropriate term—“fat pad-derived cells” or “fat pad aspirate concentrate.” We look forward to their response to our concerns.

      References

        • Koh Y.-G.
        • Jo S.-B.
        • Kwon O.-R.
        • et al.
        Mesenchymal stem cell injections improve symptoms of knee osteoarthritis.
        Arthroscopy. 2013; 29: 748-755
        • Gimble J.M.
        • Bunnell B.A.
        • Chiu E.S.
        • Guilak F.
        Concise review: Adipose-derived stromal vascular fraction cells and stem cells: Let's not get lost in translation.
        Stem Cells. 2011; 29: 749-754
        • Buda R.
        • Vannini F.
        • Cavallo M.
        • Grigolo B.
        • Cenacchi A.
        • Giannini S.
        Osteochondral lesions of the knee: A new one-step repair technique with bone-marrow-derived cells.
        J Bone Joint Surg Am. 2010; 92: 2-11
        • English A.
        • Jones E.A.
        • Corscadden D.
        • et al.
        A comparative assessment of cartilage and joint fat pad as a potential source of cells for autologous therapy development in knee osteoarthritis.
        Rheumatology (Oxford). 2007; 46: 1676-1683
        • Wickham M.Q.
        • Erickson G.R.
        • Gimble J.M.
        • Vail T.P.
        • Guilak F.
        Multipotent stromal cells derived from the infrapatellar fat pad of the knee.
        Clin Orthop Relat Res. 2003; : 196-212

      Linked Article

      • Mesenchymal Stem Cell Injections Improve Symptoms of Knee Osteoarthritis
        ArthroscopyVol. 29Issue 4
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          The purpose of this study was to evaluate the clinical and imaging results of patients who received intra-articular injections of autologous mesenchymal stem cells for the treatment of knee osteoarthritis.
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      • Authors' Reply
        ArthroscopyVol. 30Issue 4
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          We appreciate the interesting and perceptive comments by Ha and Park regarding our recent study. The review's primary concern is the terms “fat pad–derived mesenchymal stem cells (MSCs)” and “fat pad aspirate concentrate” or “fat pad–derived cells.” To use the term MSCs, the cells should possess the following characteristics: self-renewal, the expression of specific cell surface markers, and the capacity for multilineage differentiation. In the “Methods” section of our article, we briefly described the sample collection method and MSC isolation technique.
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