Adipose-derived stem cells in the treatment of knee osteoarthritis: from extraction methods to the preparation of the transplant
DOI:
https://doi.org/10.33448/rsd-v11i1.24669Keywords:
Osteoarthritis; Knee; Mesenchymal stem cells; Adipose tissue.Abstract
Introduction: Recent studies have investigated the use of adipose tissue as source of mesenchymal stem cells in the treatment of knee osteoarthritis in humans. However, there are still several protocols being performed. Objective: Analyze the protocols published in the literature in the last ten years and to investigate how they are being carried out and if they are following the criteria adopted by the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT). Methodology: Articles from the PubMed, ScienceDirect and Lilacs database published in January / 2010 until the present time, which were evaluated in order to investigate the use of adipose-derived stem cells in the treatment of knee osteoarthritis. Results: Thirty four articles were evaluated in its entiraty. The abdominal area was the most choosen to do the liposuction, however the quantities of adipose tissue removed and the number of cells transplanted was variable. It is hightlited the enzimatic digestion of adipose tissue with collagenase as extraction method. Only 14 articles complied all the 3 criteria required to prove the real presence of mesenchymal stem cells in the samples that was transplanted. However, all the articles showed improvement of function and pain. Final considerations: Thus, even the results found are promising, the evidence is still limited in humans and the variability of the methodology makes it difficult to standardize the technique, also its implementation as a reference in the treatment of knee osteoarthritis.
References
Aronowitz, J. A., Lockhart, R. A., & Hakakian, C. S. (2015). Mechanical versus enzymatic isolation of stromal vascular fraction cells from adipose tissue. Springerplus, 4(1), 713.
Bansal, H., Comella, K., Leon, J., Verma, P., Agrawal, D., Koka, P., & Ichim, T. (2017). Intra-articular injection in the knee of adipose derived stromal cells (stromal vascular fraction) and platelet rich plasma for osteoarthritis. Journal of translational medicine, 15(1), 141.
Bianchi, F., Maioli, M., Leonardi, E., Olivi, E., Pasquinelli, G., Valente, S., . . . Tremolada, C. (2013). A new nonenzymatic method and device to obtain a fat tissue derivative highly enriched in pericyte-like elements by mild mechanical forces from human lipoaspirates. Cell transplantation, 22(11), 2063-2077.
Boller, C. E. P., & Lopes, F. d. O. (2021). Intra-articular injection of platelet-rich plasma for knee osteoarthritis: scientific technical opinion on the use. Research, Society and Development, 10(1), e15710111606. https://doi.org/10.33448/rsd-v10i1.11606
Bora, P., & Majumdar, A. S. (2017). Adipose tissue-derived stromal vascular fraction in regenerative medicine: a brief review on biology and translation. Stem cell research & therapy, 8(1), 145.
Bourin, P., Bunnell, B. A., Casteilla, L., Dominici, M., Katz, A. J., March, K. L., . . . Gimble, J. M. (2013). 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, 15(6), 641-648.
Brown, L. L. (2018). Adipose-Derived Stromal Stem Cells. In Advanced Procedures for Pain Management (pp. 489-507). Springer.
Bui, K. H.-T., Duong, T. D., Nguyen, N. T., Nguyen, T. D., Le, V. T., Mai, V. T., . . . Van Pham, P. (2014). Symptomatic knee osteoarthritis treatment using autologous adipose derived stem cells and platelet-rich plasma: a clinical study. Biomedical Research and Therapy, 1(01), 02-08.
Caplan, A. I., & Dennis, J. E. (2006). Mesenchymal stem cells as trophic mediators. Journal of cellular biochemistry, 98(5), 1076-1084.
Cattaneo, G., De Caro, A., Napoli, F., Chiapale, D., Trada, P., & Camera, A. (2018). Micro-fragmented adipose tissue injection associated with arthroscopic procedures in patients with symptomatic knee osteoarthritis. BMC musculoskeletal disorders, 19(1), 176.
Chaput, B., Bertheuil, N., Escubes, M., Grolleau, J.-L., Garrido, I., Laloze, J., . . . Varin, A. (2016). Mechanically isolated stromal vascular fraction provides a valid and useful collagenase-free alternative technique: A comparative study. Plastic and reconstructive surgery, 138(4), 807-819.
Cooper, C., Javaid, M. K., & Arden, N. (2014). Epidemiology of osteoarthritis. In Atlas of osteoarthritis (pp. 21-36). Springer.
Coughlin, R. P., Oldweiler, A., Mickelson, D. T., & Moorman III, C. T. (2017). Adipose-Derived Stem Cell Transplant Technique for Degenerative Joint Disease. Arthroscopy techniques, 6(5), e1761-e1766.
Dominici, M., Le Blanc, K., Mueller, I., Slaper-Cortenbach, I., Marini, F., Krause, D., . . . Horwitz, E. (2006). Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy, 8(4), 315-317.
Fodor, P. B., & Paulseth, S. G. (2015). Adipose derived stromal cell (ADSC) injections for pain management of osteoarthritis in the human knee joint. Aesthetic surgery journal, 36(2), 229-236.
Food, & Administration, D. (2014). Minimal manipulation of human cells, tissues, and cellular and tissue‐based products; draft guidance for industry and Food and Drug Administration staff. Dec. http://www. fda. gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/CellularandGeneTherapy/ucm427692. htm.
Fraser, J., Wulur, I., Alfonso, Z., Zhu, M., & Wheeler, E. (2007). Differences in stem and progenitor cell yield in different subcutaneous adipose tissue depots. Cytotherapy, 9(5), 459-467.
Freitag, J., Bates, D., Wickham, J., Shah, K., Huguenin, L., Tenen, A., . . . Boyd, R. (2019). Adipose-derived mesenchymal stem cell therapy in the treatment of knee osteoarthritis: a randomized controlled trial. Regenerative medicine(0).
Gibbs, N., Diamond, R., Sekyere, E. O., & Thomas, W. D. (2015). Management of knee osteoarthritis by combined stromal vascular fraction cell therapy, platelet-rich plasma, and musculoskeletal exercises: a case series. Journal of pain research, 8, 799.
Hong, Z., Chen, J., Zhang, S., Zhao, C., Bi, M., Chen, X., & Bi, Q. (2018). Intra-articular injection of autologous adipose-derived stromal vascular fractions for knee osteoarthritis: a double-blind randomized self-controlled trial. International orthopaedics, 1-12.
Hudetz, D., Borić, I., Rod, E., Jeleč, Ž., Radić, A., Vrdoljak, T., . . . Plečko, M. (2017). The effect of intra-articular injection of autologous microfragmented fat tissue on proteoglycan synthesis in patients with knee osteoarthritis. Genes, 8(10), 270.
Jo, C. H., Chai, J. W., Jeong, E. C., Oh, S., Shin, J. S., Shim, H., & Yoon, K. S. (2017). Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: a 2-year follow-up study. The American journal of sports medicine, 45(12), 2774-2783.
Jo, C. H., Lee, Y. G., Shin, W. H., Kim, H., Chai, J. W., Jeong, E. C., . . . Shin, I. S. (2014). Intra‐articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: a proof‐of‐concept clinical trial. Stem cells, 32(5), 1254-1266.
Kim, Y., Choi, Y., Lee, S., Kwon, O., Suh, D., Heo, D., & Koh, Y. (2016). Assessment of clinical and MRI outcomes after mesenchymal stem cell implantation in patients with knee osteoarthritis: a prospective study. Osteoarthritis and cartilage, 24(2), 237-245.
Kim, Y. S., Choi, Y. J., & Koh, Y. G. (2015). Mesenchymal stem cell implantation in knee osteoarthritis: an assessment of the factors influencing clinical outcomes. The American journal of sports medicine, 43(9), 2293-2301.
Kim, Y. S., Choi, Y. J., Suh, D. S., Heo, D. B., Kim, Y. I., Ryu, J.-S., & Koh, Y. G. (2015). Mesenchymal stem cell implantation in osteoarthritic knees: is fibrin glue effective as a scaffold? The American journal of sports medicine, 43(1), 176-185.
Kim, Y. S., Kwon, O. R., Choi, Y. J., Suh, D. S., Heo, D. B., & Koh, Y. G. (2015). Comparative matched-pair analysis of the injection versus implantation of mesenchymal stem cells for knee osteoarthritis. The American journal of sports medicine, 43(11), 2738-2746.
Koh, Y.-G., & Choi, Y.-J. (2012). Infrapatellar fat pad-derived mesenchymal stem cell therapy for knee osteoarthritis. The Knee, 19(6), 902-907.
Koh, Y.-G., Choi, Y.-J., Kwon, S.-K., Kim, Y.-S., & Yeo, J.-E. (2015). Clinical results and second-look arthroscopic findings after treatment with adipose-derived stem cells for knee osteoarthritis. Knee Surgery, Sports Traumatology, Arthroscopy, 23(5), 1308-1316.
Koh, Y.-G., Jo, S.-B., Kwon, O.-R., Suh, D.-S., Lee, S.-W., Park, S.-H., & Choi, Y.-J. (2013). Mesenchymal stem cell injections improve symptoms of knee osteoarthritis. Arthroscopy: The Journal of Arthroscopic & Related Surgery, 29(4), 748-755.
Koh, Y. G., Choi, Y. J., Kwon, O. R., & Kim, Y. S. (2014). Second-look arthroscopic evaluation of cartilage lesions after mesenchymal stem cell implantation in osteoarthritic knees. The American journal of sports medicine, 42(7), 1628-1637.
Kornicka, K., Marycz, K., Tomaszewski, K. A., Marędziak, M., & Śmieszek, A. (2015). The effect of age on osteogenic and adipogenic differentiation potential of human adipose derived stromal stem cells (hASCs) and the impact of stress factors in the course of the differentiation process. Oxidative Medicine and Cellular Longevity, 2015.
Labusca, L. S., Botez, P., Eloae, F. Z., & Mashayekhi, K. (2013). Stem cells derived from osteoarthritic knee mesenchymal tissues: a pilot study. European Journal of Orthopaedic Surgery & Traumatology, 23(2), 169-176.
Lapuente, J. P., Dos-Anjos, S., & Blázquez-Martínez, A. (2020). Intra-articular infiltration of adipose-derived stromal vascular fraction cells slows the clinical progression of moderate-severe knee osteoarthritis: hypothesis on the regulatory role of intra-articular adipose tissue. Journal of orthopaedic surgery and research, 15, 1-9.
Lee, C. S., Burnsed, O. A., Raghuram, V., Kalisvaart, J., Boyan, B. D., & Schwartz, Z. (2012). Adipose stem cells can secrete angiogenic factors that inhibit hyaline cartilage regeneration. Stem cell research & therapy, 3(4), 35.
Lee, W. S., Kim, H. J., Kim, K. I., Kim, G. B., & Jin, W. (2019). Intra‐Articular Injection of Autologous Adipose Tissue‐Derived Mesenchymal Stem Cells for the Treatment of Knee Osteoarthritis: A Phase IIb, Randomized, Placebo‐Controlled Clinical Trial. Stem cells translational medicine.
Lu, L., Dai, C., Zhang, Z., Du, H., Li, S., Ye, P., . . . Dong, Y. (2019). Treatment of knee osteoarthritis with intra-articular injection of autologous adipose-derived mesenchymal progenitor cells: a prospective, randomized, double-blind, active-controlled, phase IIb clinical trial. Stem cell research & therapy, 10(1), 143.
Markarian, C. F., Frey, G. Z., Silveira, M. D., Milani, A. R., Ely, P. B., Horn, A. P., . . . Camassola, M. (2014). Isolation of adipose-derived stem cells: a comparison among different methods. Biotechnology letters, 36(4), 693-702.
Mollon, B., Kandel, R., Chahal, J., & Theodoropoulos, J. (2013). The clinical status of cartilage tissue regeneration in humans. Osteoarthritis and cartilage, 21(12), 1824-1833.
Nasb, M., Liangjiang, H., Gong, C., & Hong, C. (2020). Human adipose-derived Mesenchymal stem cells, low-intensity pulsed ultrasound, or their combination for the treatment of knee osteoarthritis: study protocol for a first-in-man randomized controlled trial. BMC musculoskeletal disorders, 21(1), 1-8.
Onoi, Y., Hiranaka, T., Nishida, R., Takase, K., Fujita, M., Hida, Y., . . . Okamoto, K. (2019). Second-look arthroscopic findings of cartilage and meniscus repair after injection of adipose-derived regenerative cells in knee osteoarthrits: Report of two cases. Regenerative Therapy, 11, 212-216.
Pagano, C., Calcagno, A., Giacomelli, L., Poletti, A., Macchi, V., Vettor, R., . . . Federspil, G. (2004). Molecular and morphometric description of adipose tissue during weight changes: a quantitative tool for assessment of tissue texture. International journal of molecular medicine, 14(5), 897-902.
Pak, J., Chang, J.-J., Lee, J. H., & Lee, S. H. (2013). Safety reporting on implantation of autologous adipose tissue-derived stem cells with platelet-rich plasma into human articular joints. BMC musculoskeletal disorders, 14(1), 337.
Pak, J., Lee, J. H., Pak, N. J., Park, K. S., Jeon, J. H., Jeong, B. C., & Lee, S. H. (2018). Clinical Protocol of Producing Adipose Tissue-Derived Stromal Vascular Fraction for Potential Cartilage Regeneration. JoVE (Journal of Visualized Experiments)(139), e58363.
Pak, J., Lee, J. H., Park, K. S., Jeong, B. C., & Lee, S. H. (2016). Regeneration of cartilage in human knee osteoarthritis with autologous adipose tissue-derived stem cells and autologous extracellular matrix. BioResearch open access, 5(1), 192-200.
Pak, J., Lee, J. H., Park, K. S., Park, M., Kang, L.-W., & Lee, S. H. (2017). Current use of autologous adipose tissue-derived stromal vascular fraction cells for orthopedic applications. Journal of biomedical science, 24(1), 9.
Panni, A. S., Vasso, M., Braile, A., Toro, G., De Cicco, A., Viggiano, D., & Lepore, F. (2018). Preliminary results of autologous adipose-derived stem cells in early knee osteoarthritis: identification of a subpopulation with greater response. International orthopaedics, 1-7.
Pers, Y.-M., Rackwitz, L., Ferreira, R., Pullig, O., Delfour, C., Barry, F., . . . Bourin, P. (2016). Adipose mesenchymal stromal cell‐based therapy for severe osteoarthritis of the knee: A phase i dose‐escalation trial. Stem cells translational medicine, 5(7), 847-856.
Roato, I., Belisario, D. C., Compagno, M., Lena, A., Bistolfi, A., Maccari, L., . . . Perale, G. (2019). Concentrated adipose tissue infusion for the treatment of knee osteoarthritis: clinical and histological observations. International orthopaedics, 43(1), 15-23.
Song, Y., Du, H., Dai, C., Zhang, L., Li, S., Hunter, D. J., . . . Bao, C. (2018). Human adipose-derived mesenchymal stem cells for osteoarthritis: a pilot study with long-term follow-up and repeated injections. Regenerative medicine, 13(3), 295-307.
Spasovski, D., Spasovski, V., Baščarević, Z., Stojiljković, M., Vreća, M., Anđelković, M., & Pavlović, S. (2018). Intra‐articular injection of autologous adipose‐derived mesenchymal stem cells in the treatment of knee osteoarthritis. The journal of gene medicine, 20(1), e3002.
Stromps, J.-P., Paul, N. E., Rath, B., Nourbakhsh, M., Bernhagen, J., & Pallua, N. (2014). Chondrogenic differentiation of human adipose-derived stem cells: a new path in articular cartilage defect management? BioMed research international, 2014.
Toghraie, F., Chenari, N., Gholipour, M., Faghih, Z., Torabinejad, S., Dehghani, S., & Ghaderi, A. (2011). Treatment of osteoarthritis with infrapatellar fat pad derived mesenchymal stem cells in Rabbit. The Knee, 18(2), 71-75.
Tsubosaka, M., Matsumoto, T., Sobajima, S., Matsushita, T., Iwaguro, H., & Kuroda, R. (2020). The influence of adipose-derived stromal vascular fraction cells on the treatment of knee osteoarthritis. BMC musculoskeletal disorders, 21(1), 1-10.
Van Pham, P., Hong-Thien Bui, K., Quoc Ngo, D., Tan Khuat, L., & Kim Phan, N. (2013). Transplantation of nonexpanded adipose stromal vascular fraction and platelet-rich plasma for articular cartilage injury treatment in mice model. Journal of Medical Engineering, 2013.
Yokota, N., Hattori, M., Ohtsuru, T., Otsuji, M., Lyman, S., Shimomura, K., & Nakamura, N. (2019). Comparative clinical outcomes after intra-articular injection with adipose-derived cultured stem cells or noncultured stromal vascular fraction for the treatment of knee osteoarthritis. The American journal of sports medicine, 47(11), 2577-2583.
Yokota, N., Yamakawa, M., Shirata, T., Kimura, T., & Kaneshima, H. (2017). Clinical results following intra-articular injection of adipose-derived stromal vascular fraction cells in patients with osteoarthritis of the knee. Regenerative Therapy, 6, 108-112.
Zuk, P. A., Zhu, M., Mizuno, H., Huang, J., Futrell, J. W., Katz, A. J., . . . Hedrick, M. H. (2001). Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue engineering, 7(2), 211-228.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2022 Laynna de Carvalho Schweich-Adami; Larissa Corrêa Hermeto; Silvana Marques Caramalac; Andréia Conceição Milan Brochado Antoniolli-Silva; Rodrigo Juliano Oliveira
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
1) Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
2) Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
3) Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.
