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Limited evidence for adipose-derived stem cell therapy on the treatment of osteoarthritis

  • Knee
  • Published:
Knee Surgery, Sports Traumatology, Arthroscopy Aims and scope

Abstract

Purpose

The purpose of this systematic review is to evaluate the effects of adipose derived mesenchymal stem cells (ADSCs) in the treatment of osteoarthritis (OA) in the clinical setting.

Methods

A literature search was performed in the MEDLINE, EMBASE, and The Cochrane Library Database up to January 2017 for inclusion and exclusion criteria. Criteria for inclusion were clinical studies demonstrating the effects of ADSCs on OA, and written in English. The following variables were analyzed: donor site, volume of adipose tissue, preparation of ADSCs, clinical outcomes, and complication rate.

Results

Sixteen studies (knee: 14 studies, multiple joints: 1 study, ankle: 1 study) were included in this systematic review. All of the studies prepared ADSCs in the form of the stromal vascular fraction (SVF). Inconsistencies between studies were found with regards to reported clinical variability, donor sites of SVF, and reported clinical outcomes. Nine studies used either platelet-rich plasma (PRP) (7/16) or fibrin (4/16) or both PRP and Fibrin (1/16), as an adjunct at time of SVF injection. All of the studies reported an improvement in clinical outcomes with the use of SVF. Five studies reported a 90% satisfaction rate, and no study reported any complications with liposuction. Five studies reported on complications, with a 5% incidence of swelling and pain.

Conclusions

This systematic review demonstrated that ADSCs are currently used in the form of SVF. While SVF may produce favorable clinical outcomes with minimal risk of side effects on osteoarthritis, the variability in the data and the use of biological adjuvants have confounded the effectiveness of ADSCs. This study will help surgeons understand the limitations in the literature on ADSCs.

Level of evidence

Level IV, systematic review of level IV studies.

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References

  1. Creamer P, Hochberg MC (1997) Osteoarthritis. Lancet 350:503–509

    Article  CAS  Google Scholar 

  2. Kim YS, Choi YJ, Suh DS, Heo DB, Kim YI, Ryu JS, Koh YG (2015) Mesenchymal stem cell implantation in osteoarthritic knees: is fibrin glue effective as a scaffold? Am J Sports Med 43:176–185

    Article  Google Scholar 

  3. Erickson GR, Alexopoulos LG, Guilak F (2001) Hyper-osmotic stress induces volume change and calcium transients in chondrocytes by transmembrane, phospholipid, and G-protein pathways. J Biomech 34:1527–1535

    Article  CAS  Google Scholar 

  4. Gupta PK, Das AK, Chullikana A, Majumdar AS (2012) Mesenchymal stem cells for cartilage repair in osteoarthritis. Stem Cell Res Ther 3:25

    Article  CAS  Google Scholar 

  5. Chen YC, Chen CH, Chen PL, Huang IY, Shen YS, Chen CM (2006) Donor site morbidity after harvesting of proximal tibia bone. Head Neck 28:496–500

    Article  Google Scholar 

  6. Wright JG, Swiontkowski MF, Heckman JD (2003) Introducing levels of evidence to the journal. J Bone Joint Surg Am 85:1–3

    Article  Google Scholar 

  7. Hass R, Kasper C, Bohm S, Jacobs R (2011) Different populations and sources of human mesenchymal stem cells (MSC): a comparison of adult and neonatal tissue-derived MSC. Cell Commun Signal 9:12

    Article  CAS  Google Scholar 

  8. Nathan S, Das De S, Thambyah A, Fen C, Goh J, Lee EH (2003) Cell-based therapy in the repair of osteochondral defects: a novel use for adipose tissue. Tissue Eng 9:733–744

    Article  CAS  Google Scholar 

  9. Hennig T, Lorenz H, Thiel A, Goetzke K, Dickhut A, Geiger F, Richter W (2007) Reduced chondrogenic potential of adipose tissue derived stromal cells correlates with an altered TGFbeta receptor and BMP profile and is overcome by BMP-6. J Cell Physiol 211:682–691

    Article  CAS  Google Scholar 

  10. Maredziaki M, Marycz K, Tomaszewski KA, Kornicka K, Henry BM (2016) The influence of aging on the regenerative potential of human adipose derived mesenchymal stem cells. Stem Cells Int 2016:2152435

    Google Scholar 

  11. Van Pham P, Bui K, Ngo DQ, Vu NB, Truong NH, Phan NL, Le DM, Duong TD, Nguyen TD, Le VT, Phan NK (2013) Activated platelet-rich plasma improves adipose-derived stem cell transplantation efficiency in injured articular cartilage. Stem Cell Res Ther 4:91

    Article  Google Scholar 

  12. Soriano RA, Lamblet H, Mohammedi SA, Torfi H (2013) Optimization of Roche Liberase TM research grade in the enzymatic digestion of human adipose tissue for the isolation of stem and regenerative cells. Cell Isolation Application Note No. 3. 2013

  13. Black LL, Gaynor J, Gahring D, Adams C, Aron D, Harman S, Gingerich DA, Harman R (2007) Effect of adipose-derived mesenchymal stem and regenerative cells on lameness in dogs with chronic osteoarthritis of the coxofemoral joints: a randomized, double-blinded, multicenter, controlled trial. Vet Ther 8:272–284

    PubMed  Google Scholar 

  14. Mei L, Shen B, Ling P, Liu S, Xue J, Liu F, Shao H, Chen J, Ma A, Liu X (2017) Culture-expanded allogenic adipose tissue-derived stem cells attenuate cartilage degeneration in an experimental rat osteoarthritis model. PLoS One 18:12

    Google Scholar 

  15. Slim K, Nini E, Forestier D, Kwiatkowski F, Panis Y, Chipponi J (2003) Methodological index for non-randomized studies (MINORS): development and validation of a new instrument. ANZ J Surg 73(9):712–716

    Article  Google Scholar 

  16. Hannon CP, Murawski CD, Fansa AM, Smyth NA, Do H, Kennedy JG (2013) Microfracture for osteochondral lesions of the talus: a systematic review of reporting of outcome data. Am J Sports Med 41:689–695

    Article  Google Scholar 

  17. Kim YS, Choi YJ, Koh YG (2015) Mesenchymal stem cell implantation in knee osteoarthritis: an assessment of the factors influencing clinical outcomes. Am J Sports Med 43:2293–2301

    Article  Google Scholar 

  18. Kim YS, Choi YJ, Lee SW, Kwon OR, Suh DS, Heo DB, Koh YG (2016) Assessment of clinical and MRI outcomes after mesenchymal stem cell implantation in patients with knee osteoarthritis: a prospective study. Osteoarthr Cartil 24:237–245

    Article  CAS  Google Scholar 

  19. Kim YS, Koh YG (2016) Injection of mesenchymal stem cells as a supplementary strategy of marrow stimulation improves cartilage regeneration after lateral sliding calcaneal osteotomy for varus ankle osteoarthritis: clinical and second-look arthroscopic results. Arthroscopy 32:878–889

    Article  Google Scholar 

  20. Kim YS, Kwon OR, Choi YJ, Suh DS, Heo DB, Koh YG (2015) Comparative matched-pair analysis of the injection versus implantation of mesenchymal stem cells for knee osteoarthritis. Am J Sports Med 43:2738–2746

    Article  Google Scholar 

  21. Koh YG, Choi YJ (2012) Infrapatellar fat pad-derived mesenchymal stem cell therapy for knee osteoarthritis. Knee 19:902–907

    Article  Google Scholar 

  22. Koh YG, Choi YJ, Kwon OR, Kim YS (2014) Second-look arthroscopic evaluation of cartilage lesions after mesenchymal stem cell implantation in osteoarthritic knees. Am J Sports Med 42:1628–1637

    Article  Google Scholar 

  23. Koh YG, Kwon OR, Kim YS, Choi YJ (2014) Comparative outcomes of open-wedge high tibial osteotomy with platelet-rich plasma alone or in combination with mesenchymal stem cell treatment: a prospective study. Arthroscopy 30:1453–1460

    Article  Google Scholar 

  24. Koh YG, Jo SB, Kwon OR, Suh DS, Lee SW, Park SH, Choi Y (2013) Mesenchymal stem cell injections improve symptoms of knee osteoarthritis. Arthroscopy 29:748–755

    Article  Google Scholar 

  25. Bui K, Duong TD, Nguyen NT, Nguyen TD, Le VT, Mai VT, Phan LC, Le DM, Ngoc NK, Van Pham P (2014) Symptomatic knee osteoarthritis treatment using autologous adipose derived stem cells and platelet-rich plasma: a clinical study. Biomed Res Ther 1(1):2–8

    Article  Google Scholar 

  26. Fodor PB, Paulseth SG (2016) Adipose derived stromal cell (ADSC) injections for pain management of osteoarthritis in the human knee joint. Aesthet Surg J 36(2):229–236

    Article  Google Scholar 

  27. Nguyen PD, Tran TD, Nguyen HT, Vu HT, Le PT, Phan NL, Vu NB, Phan NK, Van Pham P (2017) Comparative clinical observation of arthroscopic microfracture in the presence and absence of a stromal vascular fraction injection for osteoarthritis. Stem Cells Transl Med 6(1):187–195

    Article  Google Scholar 

  28. Pak J, Chang JJ, Lee JH, Lee SH (2013) Safety reporting on implantation of autologous adipose tissue-derived stem cells with platelet-rich plasma into human articular joints. BMC Musculoskelet Disord 1 14:337

    Article  Google Scholar 

  29. Koh YG, Choi YJ, Kwon SK, Kim YS, Yeo JE (2015) Clinical results and second-look arthroscopic findings after treatment with adipose-derived stem cells for knee osteoarthritis. Knee Surg Sports Traumatol Arthrosc 23:1308–1316

    Article  Google Scholar 

  30. Koh YG, Kwon OR, Kim YS, Choi YJ, Tak DH (2016) Adipose-derived mesenchymal stem cells with microfracture versus microfracture alone: 2-year follow-up of a prospective randomized trial. Arthroscopy 32:97–109

    Article  Google Scholar 

  31. Pers YM, Rackwitz L, Ferreira R, Pullig O, Delfour C, Barry F, Sensebe L, Casteilla L, Fleury S, Bourin P, Noël D, Canovas F, Cyteval C, Lisignoli G, Schrauth J, Haddad D, Domergue S, Noeth U, Jorgensen C (2016) Adipose mesenchymal stromal cell-based therapy for severe osteoarthritis of the knee: a phase I dose-escalation trial. Stem Cells Transl Med 5(7):847–856

    Article  Google Scholar 

  32. Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, Alfonso ZC, Fraser JK, Benhaim P, Hedrick MH (2002) Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 13:4279–4295

    Article  CAS  Google Scholar 

  33. Rodbell M, Jones AB (1966) Metabolism of isolated fat cells. 3. The similar inhibitory action of phospholipase C (Clostridium perfringens alpha toxin) and of insulin on lipolysis stimulated by lipolytic hormones and theophylline. J Biol Chem 241:140–142

    CAS  PubMed  Google Scholar 

  34. Krüger JP, Freymannx U, Vetterlein S, Neumann K, Endres M, Kaps C (2013) Bioactive factors in platelet-rich plasma obtained by apheresis. Transfus Med Hemother 40:432–440

    Article  Google Scholar 

  35. Schreml S, Babilas P, Fruth S, Orso E, Schmitz G, Mueller MB, Nerlich M, Pranti L (2009) Harvesting human adipose tissue-derived adult stem cells: resection versus liposuction. Cytotherapy 11:947–957

    Article  CAS  Google Scholar 

  36. Khoshbin A, Leroux T, Wasserstein D, Marks P, Theodoropoulos J, Ogilivie-Harris D, Gandhi R, Takhar K, Lum G, Chahal J (2013) The efficacy of platelet-rich plasma in the treatment of symptomatic knee osteoarthritis: a systematic review with quantitative synthesis. Arthroscopy 29:2037–2048

    Article  Google Scholar 

  37. Smyth NA, Murawski CD, Fortier LA, Cole BJ, Kennedy JG (2013) Platelet-rich plasma in the pathologic processes of cartilage: review of basic science evidence. Arthroscopy 29:1399–1409

    Article  Google Scholar 

  38. Pak J, Lee JH, Kartolo WA, Lee SH (2016) Cartilage regeneration in human with adipose tissue-derived stem cells: current status in clinical implications. BioMed Res Int 4702674

  39. de Windt TS, Bekkers JE, Creemers LB, Dhert WJ, Saris DB (2009) Patient profiling in cartilage regeneration: prognostic factors determining success of treatment for cartilage defects. Am J Sports Med 37(Suppl 1):58S–62S

    Google Scholar 

  40. Baer PC, Geiger H (2012) Adipose-derived mesenchymal stromal/stem cells: tissue localization, characterization, and heterogeneity. Stem Cells Int 2012:812693

    Article  Google Scholar 

  41. Martin AD, Daniel MZ, Drinkwater DT, Clarys JP (1994) Adipose tissue density, estimated adipose lipid fraction and whole body adiposity in male cadavers. Int J Obes Relat Metab Disord 18:79–83

    CAS  PubMed  Google Scholar 

  42. Iwen KA, Priewe AC, Winnefeld M, Rose C, Siemers F, Rohwedel J, Cakiroglu F, Lehnert H, Schepky A, Klein J, Kramer J (2014) Gluteal and abdominal subcutaneous adipose tissue depots as stroma cell source: gluteal cells display increased adipogenic and osteogenic differentiation potentials. Exp Dermatol 23(6):395–400

    Article  CAS  Google Scholar 

  43. Jurgens WJ, Oedayrajsingh-Varma MJ, Helder MN, Zandiehdoulabi B, Schouten TE, Kuik DJ, Ritt MJ, van Milligen FJ (2008) Effect of tissue-harvesting site on yield of stem cells derived from adipose tissue: implications for cell-based therapies. Cell Tissue Res 332(3):415–426

    Article  Google Scholar 

  44. Dragoo JL, Korotkova T, Wasterlain AS, Pouliot MA, Kim HJ, Golish SR (2012) Agre-related change of chondrogenic growth factors in platelet-rich plasma. Op Tech Orthop 22:49–55

    Article  Google Scholar 

  45. Teimourian B, Rogers WB (1989) A national survey of complications associated with suction lipectomy: a comparative study. Plast Reconstr Surg 84(4):628–631

    Article  CAS  Google Scholar 

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Funding

No funding has been received for this study.

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Authors and Affiliations

  1. Hospital for Special Surgery, 523 East 72nd Street, Suite 507, New York, NY, 10021, USA

    Eoghan T. Hurley, Youichi Yasui, Arianna L. Gianakos, Dexter Seow, Yoshiharu Shimozono & John G. Kennedy

  2. Royal College of Surgeons in Ireland, Dublin, Ireland

    Eoghan T. Hurley & Dexter Seow

  3. Department of Orthopaedic Surgery, Teikyo University School of Medicine, Tokyo, Japan

    Youichi Yasui & Yoshiharu Shimozono

  4. Department of Orthopaedic Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan

    Yoshiharu Shimozono

  5. Department of Orthopaedic Surgery, Academic Medical Center, Amsterdam, The Netherlands

    Gino M. M. J. Kerkhoffs

  6. Academic Center for Evidence Based Sports Medicine (ACES), Academic Medical Center, Amsterdam, The Netherlands

    Gino M. M. J. Kerkhoffs

  7. Amsterdam Collaboration for Health and Safety in Sports (ACHSS), Amsterdam, The Netherlands

    Gino M. M. J. Kerkhoffs

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  1. Eoghan T. Hurley
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  2. Youichi Yasui
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Corresponding author

Correspondence to John G. Kennedy.

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The authors declare that they have no conflict of interest.

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This manuscript is a systematic review and does not contain any studies with human participants or animals performed by any of the authors.

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Hurley, E.T., Yasui, Y., Gianakos, A.L. et al. Limited evidence for adipose-derived stem cell therapy on the treatment of osteoarthritis. Knee Surg Sports Traumatol Arthrosc 26, 3499–3507 (2018). https://doi.org/10.1007/s00167-018-4955-x

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  • DOI: https://doi.org/10.1007/s00167-018-4955-x

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