Abstract
Purpose
Osteoarthritis (OA) is characterized by articular cartilage degeneration and subchondral bone sclerosis. OA can benefit of non-surgical treatments with collagenase-isolated stromal vascular fraction (SVF) or cultured-expanded mesenchymal stem cells (ASCs). To avoid high manipulation of the lipoaspirate needed to obtain ASCs and SVF, we investigated whether articular infusions of autologous concentrated adipose tissue are an effective treatment for knee OA patients.
Methods
The knee of 20 OA patients was intra-articularly injected with autologous concentrated adipose tissue, obtained after centrifugation of lipoaspirate. Patients’ articular functionality and pain were evaluated by VAS and WOMAC scores at three, six and 18 months from infusion. The osteogenic and chondrogenic ability of ASCs contained in the injected adipose tissue was studied in in vitro primary osteoblast and chondrocyte cell cultures, also plated on 3D-bone scaffold. Knee articular biopsies of patients previously treated with adipose tissue were analyzed. Immunohistochemistry (IHC) and scanning electron microscopy (SEM) were performed to detect cell differentiation and tissue regeneration.
Results
The treatment resulted safe, and all patients reported an improvement in terms of pain reduction and increase of function. According to the osteogenic or chondrogenic stimulation, ASCs expressed alkaline phosphatase or aggrecan, respectively. The presence of a layer of newly formed tissue was visualized by IHC staining and SEM. The biopsy of previously treated knee joints showed new tissue formation, starting from the bone side of the osteochondral lesion.
Conclusions
Overall our data indicate that adipose tissue infusion stimulates tissue regeneration and might be considered a safe treatment for knee OA.
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References
Dunlop DD, Manheim LM, Song J, Chang RW (2003) Health care utilization among older adults with arthritis. Arthritis Rheum 49(2):164–171. https://doi.org/10.1002/art.11003
Braman JP, Bruckner JD, Clark JM, Norman AG, Chansky HA (2005) Articular cartilage adjacent to experimental defects is subject to atypical strains. Clin Orthop Relat Res (430):202–207
Coleman CM, Curtin C, Barry FP, O'Flatharta C, Murphy JM (2010) Mesenchymal stem cells and osteoarthritis: remedy or accomplice? Hum Gene Ther 21(10):1239–1250. https://doi.org/10.1089/hum.2010.138
Caplan AI (1991) Mesenchymal stem cells. J Orthop Res 9(5):641–650. https://doi.org/10.1002/jor.1100090504
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(12):4279–4295. https://doi.org/10.1091/mbc.E02-02-0105
Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, Benhaim P, Lorenz HP, Hedrick MH (2001) Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng 7(2):211–228. https://doi.org/10.1089/107632701300062859
Roato I, Alotto D, Belisario DC, Casarin S, Fumagalli M, Cambieri I, Piana R, Stella M, Ferracini R, Castagnoli C (2016) Adipose derived-mesenchymal stem cells viability and differentiating features for orthopaedic reparative applications: banking of adipose tissue. Stem Cells Int 2016:4968724. https://doi.org/10.1155/2016/4968724
Coleman SR, Saboeiro AP (2007) Fat grafting to the breast revisited: safety and efficacy. Plast Reconstr Surg 119(3):775–785; discussion 786–777. https://doi.org/10.1097/01.prs.0000252001.59162.c9
Pu LL, Coleman SR, Cui X, Ferguson RE Jr, Vasconez HC (2008) Autologous fat grafts harvested and refined by the Coleman technique: a comparative study. Plast Reconstr Surg 122(3):932–937. https://doi.org/10.1097/PRS.0b013e3181811ff0
Roato I, Belisario DC, Compagno M, Verderio L, Sighinolfi A, Mussano F, Genova T, Veneziano F, Pertici G, Perale G, Ferracini R (2018) Adipose-derived stromal vascular fraction/xenohybrid bone scaffold: an alternative source for bone regeneration. Stem Cells Int 2018:4126379. https://doi.org/10.1155/2018/4126379
Pertici G, Rossi F, Casalini T, Perale G (2014) Composite polymer-coated mineral grafts for bone regeneration: material characterisation and model study. Ann Oral Maxillofac Surg 2(1):4
Pak J, Lee JH, Park KS, Park M, Kang LW, Lee SH (2017) Current use of autologous adipose tissue-derived stromal vascular fraction cells for orthopedic applications. J Biomed Sci 24(1):9. https://doi.org/10.1186/s12929-017-0318-z
Perdisa F, Gostynska N, Roffi A, Filardo G, Marcacci M, Kon E (2015) Adipose-derived mesenchymal stem cells for the treatment of articular cartilage: a systematic review on preclinical and clinical evidence. Stem Cells Int 2015:597652. https://doi.org/10.1155/2015/597652
Pers YM, Rackwitz L, Ferreira R, Pullig O, Delfour C, Barry F, Sensebe L, Casteilla L, Fleury S, Bourin P, Noel 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. https://doi.org/10.5966/sctm.2015-0245
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. https://doi.org/10.5966/sctm.2016-0023
Centeno CJ, Al-Sayegh H, Freeman MD, Smith J, Murrell WD, Bubnov R (2016) A multi-center analysis of adverse events among two thousand, three hundred and seventy two adult patients undergoing adult autologous stem cell therapy for orthopaedic conditions. Int Orthop 40(8):1755–1765. https://doi.org/10.1007/s00264-016-3162-y
Del Vecchio D (2009) Breast reconstruction for breast asymmetry using recipient site pre-expansion and autologous fat grafting: a case report. Ann Plast Surg 62(5):523–527. https://doi.org/10.1097/SAP.0b013e3181a23f08
Al Sufyani MA, Al Hargan AH, Al Shammari NA (2016) Autologous fat transfer for breast augmentation: a review. Dermatol Surg 42(11):1235–1242. https://doi.org/10.1097/DSS.0000000000000791
Laloze J, Varin A, Gilhodes J, Bertheuil N, Grolleau JL, Brie J, Usseglio J, Sensebe L, Filleron T, Chaput B (2018) Cell-assisted lipotransfer: friend or foe in fat grafting? Systematic review and meta-analysis. J Tissue Eng Regen Med 12(2):e1237–e1250. https://doi.org/10.1002/term.2524
Liu SY, He YB, Deng SY, Zhu WT, Xu SY, Ni GX (2017) Exercise affects biological characteristics of mesenchymal stromal cells derived from bone marrow and adipose tissue. Int Orthop 41(6):1199–1209. https://doi.org/10.1007/s00264-017-3441-2
Song Y, Tang Y, Song J, Lei M, Liang P, Fu T, Su X, Zhou P, Yang L, Huang E (2018) Cyclic mechanical stretch enhances BMP9-induced osteogenic differentiation of mesenchymal stem cells. Int Orthop 42(4):947–955. https://doi.org/10.1007/s00264-018-3796-z
Moseley JB, O'Malley K, Petersen NJ, Menke TJ, Brody BA, Kuykendall DH, Hollingsworth JC, Ashton CM, Wray NP (2002) A controlled trial of arthroscopic surgery for osteoarthritis of the knee. N Engl J Med 347(2):81–88. https://doi.org/10.1056/NEJMoa013259
Amin NH, Hussain W, Ryan J, Morrison S, Miniaci A, Jones MH (2017) Changes within clinical practice after a randomized controlled trial of knee arthroscopy for osteoarthritis. Orthop J Sports Med 5(4):2325967117698439. https://doi.org/10.1177/2325967117698439
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(5):1308–1316. https://doi.org/10.1007/s00167-013-2807-2
Krusche-Mandl I, Schmitt B, Zak L, Apprich S, Aldrian S, Juras V, Friedrich KM, Marlovits S, Weber M, Trattnig S (2012) Long-term results 8 years after autologous osteochondral transplantation: 7 T gagCEST and sodium magnetic resonance imaging with morphological and clinical correlation. Osteoarthr Cartil 20(5):357–363
Lalande C, Miraux S, Derkaoui SM, Mornet S, Bareille R, Fricain JC, Franconi JM, Le Visage C, Letourneur D, Amedee J, Bouzier-Sore AK (2011) Magnetic resonance imaging tracking of human adipose derived stromal cells within three-dimensional scaffolds for bone tissue engineering. Eur Cell Mater 21:341–354
Mussano F, Genova T, Corsalini M, Schierano G, Pettini F, Di Venere D, Carossa S (2017) Cytokine, chemokine, and growth factor profile characterization of undifferentiated and osteoinduced human adipose-derived stem cells. Stem Cells Int 2017:6202783. https://doi.org/10.1155/2017/6202783
Bosetti M, Borrone A, Follenzi A, Messaggio F, Tremolada C, Cannas M (2016) Human lipoaspirate as autologous injectable active scaffold for one-step repair of cartilage defects. Cell Transplant 25(6):1043–1056. https://doi.org/10.3727/096368915X689514
Murphy JM, Dixon K, Beck S, Fabian D, Feldman A, Barry F (2002) Reduced chondrogenic and adipogenic activity of mesenchymal stem cells from patients with advanced osteoarthritis. Arthritis Rheum 46(3):704–713. https://doi.org/10.1002/art.10118
Hernigou P, Auregan JC, Dubory A, Flouzat-Lachaniette CH, Chevallier N, Rouard H (2018) Subchondral stem cell therapy versus contralateral total knee arthroplasty for osteoarthritis following secondary osteonecrosis of the knee. Int Orthop. https://doi.org/10.1007/s00264-018-3916-9
Kubosch EJ, Heidt E, Niemeyer P, Bernstein A, Sudkamp NP, Schmal H (2017) In-vitro chondrogenic potential of synovial stem cells and chondrocytes allocated for autologous chondrocyte implantation - a comparison: sSynovial stem cells as an alternative cell source for autologous chondrocyte implantation. Int Orthop 41(5):991–998. https://doi.org/10.1007/s00264-017-3400-y
Acknowledgments
This work was supported by Compagnia di San Paolo and CRT Foundations, Banca d’Italia, and Fondazione Ricerca Molinette ONLUS. The authors thank Dr. Dario Picenoni, at SAMM (Politecnico di Milano), for his technical contribution to SEM analyses, Dr. Francesca Veneziano for immunohistochemistry.
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Giuseppe Perale is affiliated to the Company manufacturing the bone substitute used in this study
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Roato, I., Belisario, D.C., Compagno, M. et al. Concentrated adipose tissue infusion for the treatment of knee osteoarthritis: clinical and histological observations. International Orthopaedics (SICOT) 43, 15–23 (2019). https://doi.org/10.1007/s00264-018-4192-4
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DOI: https://doi.org/10.1007/s00264-018-4192-4