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Letter to the Editor| Volume 24, ISSUE 7, P1302-1303, July 2016

Stem cells for cartilage repair: what exactly were used for treatment, cultured adipose-derived stem cells or the unexpanded stromal vascular fraction?

  • J.I. Lee
    Correspondence
    Address correspondence and reprint requests to: J.I. Lee, Regenerative Medicine Laboratory, Center for Stem Cell Research, Department of Biomedical Science and Technology, Institute of Biomedical Science and Technology, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea. Tel: 82-2-2049-6234; Fax: 82-2-446-9001.
    Affiliations
    Regenerative Medicine Laboratory, Center for Stem Cell Research, Department of Biomedical Science and Technology, Institute of Biomedical Science and Technology, Konkuk University, Seoul, Republic of Korea
    Department of Veterinary Medicine, College of Veterinary Medicine, Konkuk University, Seoul, Republic of Korea
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  • E. Balolong Jr.
    Affiliations
    Regenerative Medicine Laboratory, Center for Stem Cell Research, Department of Biomedical Science and Technology, Institute of Biomedical Science and Technology, Konkuk University, Seoul, Republic of Korea
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  • Y. Han
    Affiliations
    Regenerative Medicine Laboratory, Center for Stem Cell Research, Department of Biomedical Science and Technology, Institute of Biomedical Science and Technology, Konkuk University, Seoul, Republic of Korea
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  • S. Lee
    Correspondence
    Address correspondence and reprint requests to: S. Lee, Regenerative Medicine Laboratory, Center for Stem Cell Research, Department of Biomedical Science and Technology, Institute of Biomedical Science and Technology, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea. Tel: 82-2-2049-6234; Fax: 82-2-446-9001.
    Affiliations
    Regenerative Medicine Laboratory, Center for Stem Cell Research, Department of Biomedical Science and Technology, Institute of Biomedical Science and Technology, Konkuk University, Seoul, Republic of Korea
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Open ArchivePublished:March 02, 2016DOI:https://doi.org/10.1016/j.joca.2016.01.990
Stem cells for cartilage repair: what exactly were used for treatment, cultured adipose-derived stem cells or the unexpanded stromal vascular fraction?
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Next ArticleResponse to Letter to the Editor: the use of the term “mesenchymal stem cells” in our article is appropriate based on our laboratory study and the review of the literatures

      Keywords

      Dear Editors,
      We read with interest the recent article entitled “Assessment of clinical and MRI outcomes after mesenchymal stem cell implantation in patients with knee osteoarthritis: a prospective study” by Kim et al. In this paper, the authors have concluded that the use of mesenchymal stem cells (MSCs) to repair cartilage lesions is feasible as demonstrated by their clinical and MRI data.
      We noticed, however, that the authors misreported the fraction they used for their therapy. According to the joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT), the pellet obtained after subjecting the adipose tissue to enzymatic digestion (usually collagenase), filtration and subsequently separated further from the mature adipocytes through centrifugation is referred to as the heterogeneous stromal vascular fraction (SVF) with the adipose-derived stem cells (ASCs) as among the subset of cells within the SVF. The ASCs identity can be verified when cultured as they are plastic-adherent, exhibit multi-potency and express specific surface markers
      • Bourin P.
      • Bunnell B.
      • Casteilla L.
      • Dominici M.
      • Katz A.J.
      • March K.L.
      • et al.
      Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal/stem cells: a joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT).
      Cytotherapy. 2013; 15: 641-648https://doi.org/10.1016/j.jcyt.2013.02.006
      . Several terms have been used to identify these adherent cells and in support to the consensus reached by IFATS to unify the term
      • Bunnell B.
      • Flaat M.
      • Gagliardi C.
      • Patel B.
      • Ripoll C.
      Adipose-derived stem cells: isolation, expansion and differentiation.
      Methods. 2008; 45: 115-120https://doi.org/10.1016/j.ymeth.2008.03.006
      we will call the MSCs referred to in this article as ASCs. Likewise, we encourage the authors to use the same.
      In the methods section the authors stated “we aimed to collect 140 cc liposuctioned adipose tissue: 120 cc was used for implantation and the remaining 20 cc was analyzed to examine the plastic adherent cells that form the fibroblast colony forming units (CFU-F) and confirm the mutilineage differentiation of adipose-derived stem cells”. There is no other way this can be understood but to mean that the adipose tissue collected were divided into two portions. One portion was used for transplantation and upon review of their procedure which was adapted from Zuk et al.
      • Zuk P.
      • Zhu M.
      • Mizuno H.
      • Huang J.
      • Futrell J.W.
      • Katz A.J.
      Multilineage cells from human adipose tissue: implications for cell-based therapies.
      Tissue Eng. 2001; 7: 211-228
      , this clearly was the unexpanded SVF. Although they were successful in showing that adherent cells upon culture were indeed ASCs by using another portion of the collected adipose tissue, this does not necessarily mean that the SVF works the same way as when using the expanded ASCs cultured from the SVF. The uncultured ASCs in the SVF when characterized according to their surface markers have different phenotypes compared with cultured ASCs
      • Feisst V.
      • Meidinger S.
      • Locke M.B.
      From bench to bedside: use of human adipose-derived stem cells.
      Stem Cells Cloning. 2015 Nov 2; 8: 149-162https://doi.org/10.2147/SCCAA.S64373
      .
      Also, in the methods section particularly on describing their surgical technique, the authors acknowledged that the SVF was used as they wrote “first, the cell suspension (stromal vascular fraction cells containing MSCs) was loaded into the thrombin solution in a 1:1 mixture ratio” but later in the paragraph they refer this suspension wholly as stem cells when they wrote “implantation of this cell thrombin-fibrinogen suspension (i.e., MSCs mixed with fibrin glue) under arthroscopic guidance after the arthroscopic fluid was extracted”. The term stem cell was reflected in the title and the abstract with no reference to the SVF which is incorrect and will confuse the readers and patients.
      Researches, reviewers and editors are encouraged to look closely at the true identity of the cells using the characteristics put forward through the IFATS and ISCT joint statement. While there are published reports declaring the use of ASCs but in fact what were used was the SVF

      Balolong E, Lee S, Nemeno JG, Lee JI. Are they really stem cells? Scrutinizing the identity of cells and the quality of reporting in the use of adipose tissue-derived stem cells. Stem Cells Int. Available online 9 September 2015. Article ID 186965.

      , other authors using the same material as used in this study refer this correctly as the SVF rather than ASCs
      • Michalek A.J.
      • Moster R.
      • Lukac L.
      • Proefrock K.
      Autologous adipose tissue-derived stromal vascular fraction cells application in patients with osteoarthritis.
      Cell Transplant. 2015; : 1-36https://doi.org/10.3727/096368915X686760
      , 
      • Chatterjee S.
      • Laliberte M.
      • Blelloch S.
      • Ratanshi I.
      • Safneck J.
      • Buchel E.
      • et al.
      Adipose-derived stromal vascular fraction differentially expands breast progenitors in tissue adjacent to tumors compared to healthy breast tissue.
      Plast Reconstr Surg. 2015; 136: 414e-425ehttps://doi.org/10.1097/PRS.0000000000001635
      in their title and abstract. We cannot but emphasize the importance of having an accurate title and abstract as these highlights the objectives, methods, results and conclusion of the study.
      We request therefore the authors to clarify whether the material they used for therapy are the unexpanded SVF or the cultured ASCs. We expect modifications in the term “MSC implantation” in their title, abstract and conclusion if SVFs instead of ASCs were actually utilized. We enjoin the research community to be clear and transparent on the materials used to contribute to understanding the real therapeutic potential of SVFs or ASCs.

      Contributions

      All authors were involved in the manuscript conception, design, drafting and revising, and final approval of the submitted version.

      Competing interests

      None.

      Funding source

      This paper was supported by Konkuk University in 2015.

      Acknowledgments

      None.

      References

        • Bourin P.
        • Bunnell B.
        • Casteilla L.
        • Dominici M.
        • Katz A.J.
        • March K.L.
        • et al.
        Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal/stem cells: a joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT).
        Cytotherapy. 2013; 15: 641-648https://doi.org/10.1016/j.jcyt.2013.02.006
        View in Article
        • Bunnell B.
        • Flaat M.
        • Gagliardi C.
        • Patel B.
        • Ripoll C.
        Adipose-derived stem cells: isolation, expansion and differentiation.
        Methods. 2008; 45: 115-120https://doi.org/10.1016/j.ymeth.2008.03.006
        View in Article
        • Zuk P.
        • Zhu M.
        • Mizuno H.
        • Huang J.
        • Futrell J.W.
        • Katz A.J.
        Multilineage cells from human adipose tissue: implications for cell-based therapies.
        Tissue Eng. 2001; 7: 211-228
        View in Article
        • Feisst V.
        • Meidinger S.
        • Locke M.B.
        From bench to bedside: use of human adipose-derived stem cells.
        Stem Cells Cloning. 2015 Nov 2; 8: 149-162https://doi.org/10.2147/SCCAA.S64373
        View in Article

      5. Balolong E, Lee S, Nemeno JG, Lee JI. Are they really stem cells? Scrutinizing the identity of cells and the quality of reporting in the use of adipose tissue-derived stem cells. Stem Cells Int. Available online 9 September 2015. Article ID 186965.

        View in Article
        • Michalek A.J.
        • Moster R.
        • Lukac L.
        • Proefrock K.
        Autologous adipose tissue-derived stromal vascular fraction cells application in patients with osteoarthritis.
        Cell Transplant. 2015; : 1-36https://doi.org/10.3727/096368915X686760
        View in Article
        • Chatterjee S.
        • Laliberte M.
        • Blelloch S.
        • Ratanshi I.
        • Safneck J.
        • Buchel E.
        • et al.
        Adipose-derived stromal vascular fraction differentially expands breast progenitors in tissue adjacent to tumors compared to healthy breast tissue.
        Plast Reconstr Surg. 2015; 136: 414e-425ehttps://doi.org/10.1097/PRS.0000000000001635
        View in Article

      Article info

      Publication history

      Published online: March 02, 2016
      Accepted: January 10, 2016
      Received: December 16, 2015

      Identification

      DOI: https://doi.org/10.1016/j.joca.2016.01.990

      Copyright

      © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd.

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