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Journal of Translational Medicine
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Open Access 01-12-2024 | Osteoarthrosis | Research

Clinical outcomes of autologous adipose-derived mesenchymal stem cell combined with high tibial osteotomy for knee osteoarthritis are correlated with stem cell stemness and senescence

Authors: Houyi Sun, Haoxin Zhai, Kaifei Han, Heran Ma, Yi Tan, Shihao Li, Zhicheng Liu, Lei Cheng, Qunshan Lu, Libo Zhou, Peilai Liu

Published in: Journal of Translational Medicine | Issue 1/2024

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Abstract

Background

Mesenchymal stem cells (MSCs) have been proposed to treat osteoarthritis (OA) for many years. However, clinical outcomes have been inconsistent due to biological variation between patients, differences in tissue source and preparation of the MSCs, and type of donor (e.g. allogenic versus autologous). Here, we test the hypothesis that inconsistent clinical outcomes are related to variations in the stemness and senescence of the injected autologous adipose-derived (AD) MSCs.

Methods

In the prospective randomized trial, 45 knee OA patients were divided into two groups: Group 1 (n = 22) patients treated with high tibial osteotomy (HTO) alone and Group 2 (n = 23) patients treated with HTO followed by intra-articular injection of autologous AD-MSCs (HTO + AD-MSCs). MRI and X-ray were performed pre-operation and 12 months post-operation. WOMAC and VAS score were collected four times, every 6 months over a 24-month follow-up. We observed the proliferation and stemness of AD-MSCs selected from the 5 patients showing the most improvement and from the 5 patients with the least improvement, and completed further in vitro experiments including beta-galactosidase activity, reactive oxygen species and bioinformatic analysis.

Results

The results showed that patients treated with HTO + AD-MSCs had a significant reduction in knee OA severity as compared to patients treated with HTO alone. Moreover, we discovered that proliferation and colony forming efficiency of AD-MSCs selected from the 5 patients showing the most improvement performed significantly better than cells selected from the 5 patients with the least improvement. AD-MSCs from the patients with the most improvement also had lower amounts of senescent cells and intracellular reactive oxygen species.

Conclusions

Clinical outcomes of autologous AD-MSCs therapy in knee osteoarthritis are correlated with stem cell stemness and senescence. Our study highlights emerging opportunities and trends in precision medicine that could potentially improve autologous MSC-based therapies.
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Literature
1.
Ehioghae M, Vippa TK, Askins D, Slusarczyk S, Bobo E, Montoya A, Anderson D, Robinson CL, Kaye AD, Urits I. Exploring orthopedic stem-cell approaches for osteoarthritis management: current trends and future horizons. Curr Pain Headache Rep. 2024;28(1):27–35.PubMedCrossRef
2.
3.
4.
Ghanem CI, Pérez MJ, Manautou JE, Mottino AD. Acetaminophen from liver to brain: new insights into drug pharmacological action and toxicity. Pharmacol Res. 2016;109:119–31.PubMedPubMedCentralCrossRef
5.
Ekhtiari S, Haldane CE, de Sa D, Simunovic N, Musahl V, Ayeni OR. Return to work and sport following high tibial osteotomy: a systematic review. J Bone Joint Surg. 2016;98(18):1568–77.PubMedCrossRef
6.
7.
Karsdal MA, Bay-Jensen AC, Lories RJ, Abramson S, Spector T, Pastoureau P, Christiansen C, Attur M, Henriksen K, Goldring SR, Kraus V. The coupling of bone and cartilage turnover in osteoarthritis: opportunities for bone antiresorptives and anabolics as potential treatments? Ann Rheum Dis. 2014;73(2):336–48.PubMedCrossRef
8.
Yu H, Huang Y, Yang L. Research progress in the use of mesenchymal stem cells and their derived exosomes in the treatment of osteoarthritis. Ageing Res Rev. 2022;80: 101684.PubMedCrossRef
9.
Matsuta S, Endo K, Ozeki N, Nakagawa Y, Koga H, Sekiya I. Synovial mesenchymal stem cells secrete more lubricin than adipose mesenchymal stem cells after injection into rat osteoarthritis knees. Biochem Biophys Res Commun. 2024;729: 150354.PubMedCrossRef
10.
11.
Smolinska V, Debreova M, Culenova M, Csobonyeiova M, Svec A, Danisovic L. Implication of mesenchymal stem cells and their derivates for osteochondral regeneration. Int J Mol Sci. 2022;23(5):2490.PubMedPubMedCentralCrossRef
12.
Maheshwer B, Polce EM, Paul K, Williams BT, Wolfson TS, Yanke A, Verma NN, Cole BJ, Chahla J. Regenerative potential of mesenchymal stem cells for the treatment of knee osteoarthritis and chondral defects: a systematic review and meta-analysis. Arthrosc J Arthrosc Relat Surg. 2021;37(1):362–78.CrossRef
13.
Koh Y-G, Kwon O-R, Kim Y-S, Choi Y-J. Comparative outcomes of open-wedge high tibial osteotomy with platelet-rich plasma alone or in combination with mesenchymal stem cell treatment: a prospective study. Arthrosc J Arthrosc Relat Surg. 2014;30(11):1453–60.CrossRef
14.
Wakitani S, Imoto K, Yamamoto T, Saito M, Murata N, Yoneda M. Human autologous culture expanded bone marrow mesenchymal cell transplantation for repair of cartilage defects in osteoarthritic knees. Osteoarthr Cartil. 2002;10(3):199–206.CrossRef
15.
Kim YS, Koh YG. Comparative matched-pair analysis of open-wedge high tibial osteotomy with versus without an injection of adipose-derived mesenchymal stem cells for varus knee osteoarthritis: clinical and second-look arthroscopic results. Am J Sports Med. 2018;46(11):2669–77.PubMedCrossRef
16.
Coryell PR, Diekman BO, Loeser RF. Mechanisms and therapeutic implications of cellular senescence in osteoarthritis. Nat Rev Rheumatol. 2021;17(1):47–57.PubMedCrossRef
17.
18.
Pintore A, Notarfrancesco D, Zara A, Oliviero A, Migliorini F, Oliva F, Maffulli N. Intra-articular injection of bone marrow aspirate concentrate (BMAC) or adipose-derived stem cells (ADSCs) for knee osteoarthritis: a prospective comparative clinical trial. J Orthop Surg Res. 2023;18(1):350.PubMedPubMedCentralCrossRef
19.
Le Blanc K, Tammik C, Rosendahl K, Zetterberg E, Ringdén O. HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp Hematol. 2003;31(10):890–6.PubMedCrossRef
20.
Toma C, Wagner WR, Bowry S, Schwartz A, Villanueva F. Fate of culture-expanded mesenchymal stem cells in the microvasculature: in vivo observations of cell kinetics. Circ Res. 2009;104(3):398–402.PubMedCrossRef
21.
Zangi L, Margalit R, Reich-Zeliger S, Bachar-Lustig E, Beilhack A, Negrin R, Reisner Y. Direct imaging of immune rejection and memory induction by allogeneic mesenchymal stromal cells. Stem Cells. 2009;27(11):2865–74.PubMedCrossRef
22.
23.
Kim KI, Lee MC, Lee JH, Moon YW, Lee WS, Lee HJ, Hwang SC, In Y, Shon OJ, Bae KC, Song SJ, Park KK, Kim JH. Clinical efficacy and safety of the intra-articular injection of autologous adipose-derived mesenchymal stem cells for knee osteoarthritis: a phase III, randomized, double-blind, placebo-controlled trial. Am J Sports Med. 2023;51(9):2243–53.PubMedCrossRef
24.
Schumacher A, Mucha P, Puchalska I, Deptuła M, Wardowska A, Tymińska A, Filipowicz N, Mieczkowska A, Sachadyn P, Piotrowski A, Pikuła M, Cichorek M. Angiopoietin-like growth factor-derived peptides as biological activators of adipose-derived mesenchymal stromal cells. Biomed Pharmacother. 2024;177: 117052.PubMedCrossRef
25.
Lau CS, Park SY, Ethiraj LP, Singh P, Raj G, Quek J, Prasadh S, Choo Y, Goh BT. Role of adipose-derived mesenchymal stem cells in bone regeneration. Int J Mol Sci. 2024;25(12):6805.PubMedPubMedCentralCrossRef
26.
Kostecka A, Kalamon N, Skoniecka A, Koczkowska M, Skowron PM, Piotrowski A, Pikuła M. Adipose-derived mesenchymal stromal cells in clinical trials: insights from single-cell studies. Life Sci. 2024;351: 122761.PubMedCrossRef
27.
Elzainy A, El Sadik A, Altowayan WM. Comparison between the regenerative and therapeutic impacts of bone marrow mesenchymal stem cells and adipose mesenchymal stem cells pre-treated with melatonin on liver fibrosis. Biomolecules. 2024;14(3):297.PubMedPubMedCentralCrossRef
28.
Villanueva S, Carreño JE, Salazar L, Vergara C, Strodthoff R, Fajre F, Céspedes C, Sáez PJ, Irarrázabal C, Bartolucci J, Figueroa F, Vio CP. Human mesenchymal stem cells derived from adipose tissue reduce functi onal and tissue damage in a rat model of chronic renal failure. Clin Sci. 2013;125(4):199–210.CrossRef
29.
Chang D, Fan T, Gao S, Jin Y, Zhang M, Ono M. Application of mesenchymal stem cell sheet to treatment of ischemic he art disease. Stem Cell Res Ther. 2021;12(1):384.PubMedPubMedCentralCrossRef
30.
Li S, Zhang X, Liu M, Lu Q, Yu Y, Miao Z, Luo D, Han K, Li L, Qian W, Liu P. Not using a tourniquet is superior to tourniquet use for high tibial osteotomy: a prospective, randomised controlled trial. Int Orthop. 2022;46(4):823–9.PubMedCrossRef
31.
Li S, Yang J, Watson C, Lu Q, Zhang M, Miao Z, Luo D, Liu P. Drainage relieves pain without increasing post-operative blood loss in high tibial osteotomy: a prospective randomized controlled study. Int Orthop. 2020;44(6):1037–43.PubMedCrossRef
32.
Freitag J, Bates D, Wickham J, Shah K, Huguenin L, Tenen A, Paterson K, Boyd R. Adipose-derived mesenchymal stem cell therapy in the treatment of knee osteoarthritis: a randomized controlled trial. Regen Med. 2019;14(3):213–30.PubMedCrossRef
33.
Lee WS, Kim HJ, Kim KI, Kim GB, Jin W. 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 Transl Med. 2019;8(6):504–11.PubMedPubMedCentralCrossRef
34.
Mainil-Varlet P, Aigner T, Brittberg M, Bullough P, Hollander A, Hunziker E, Kandel R, Nehrer S, Pritzker K, Roberts S, Stauffer E. Histological assessment of cartilage repair: a report by the Histology Endpoint Committee of the International Cartilage Repair Society (ICRS). J Bone Joint Surg. 2003;85-A(Suppl 2):45–57.CrossRef
35.
Casula V, Hirvasniemi J, Lehenkari P, Ojala R, Haapea M, Saarakkala S, Lammentausta E, Nieminen MT. Association between quantitative MRI and ICRS arthroscopic grading of articular cartilage. Knee Surg Sports Traumatol Arthrosc. 2016;24(6):2046–54.PubMedCrossRef
36.
Brittberg M, Winalski CS. Evaluation of cartilage injuries and repair. J Bone Joint Surg. 2003;85-A(Suppl 2):58–69.CrossRef
37.
Valdes AM, Doherty S, Muir KR, Zhang W, Maciewicz RA, Wheeler M, Arden N, Cooper C, Doherty M. Genetic contribution to radiographic severity in osteoarthritis of the knee. Ann Rheum Dis. 2012;71(9):1537–40.PubMedCrossRef
38.
Collins NJ, Misra D, Felson DT, Crossley KM, Roos EM. Measures of knee function: International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Form, Knee Injury and Osteoarthritis Outcome Score (KOOS), Knee Injury and Osteoarthritis Outcome Score Physical Function Short Form (KOOS-PS), Knee Outcome Survey Activities of Daily Living Scale (KOS-ADL), Lysholm Knee Scoring Scale, Oxford Knee Score (OKS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Activity Rating Scale (ARS), and Tegner Activity Score (TAS). Arthritis Care Res. 2011;63(Suppl 11):S208–28.
39.
Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop D, Horwitz E. Minimal criteria for defining multipotent mesenchymal stromal cells. Int Soc Cell Ther Position Statement Cytother. 2006;8(4):315–7.
40.
Gong W, Xu J, Wang Y, Min Q, Chen X, Zhang W, Chen J, Zhan Q. Nuclear genome-derived circular RNA circPUM1 localizes in mitochondria and regulates oxidative phosphorylation in esophageal squamous cell carcinoma. Signal Transduct Target Ther. 2022;7(1):40.PubMedPubMedCentralCrossRef
41.
Hashimoto Y, Nishida Y, Takahashi S, Nakamura H, Mera H, Kashiwa K, Yoshiya S, Inagaki Y, Uematsu K, Tanaka Y, Asada S, Akagi M, Fukuda K, Hosokawa Y, Myoui A, Kamei N, Ishikawa M, Adachi N, Ochi M, Wakitani S. Transplantation of autologous bone marrow-derived mesenchymal stem cells under arthroscopic surgery with microfracture versus microfracture alone for articular cartilage lesions in the knee: a multicenter prospective randomized control clinical trial. Regen Ther. 2019;11:106–13.PubMedPubMedCentralCrossRef
42.
Wong KL, Lee KBL, Tai BC, Law P, Lee EH, Hui JHP. Injectable cultured bone marrow-derived mesenchymal stem cells in varus knees with cartilage defects undergoing high tibial osteotomy: a prospective, randomized controlled clinical trial with 2 years’ follow-up. Arthrosc J Arthrosc Relat Surg. 2013;29(12):2020–8.CrossRef
43.
Al-Najar M, Khalil H, Al-Ajlouni J, Al-Antary E, Hamdan M, Rahmeh R, Alhattab D, Samara O, Yasin M, Abdullah AA, Al-jabbari E, Hmaid D, Jafar H, Awidi A. Intra-articular injection of expanded autologous bone marrow mesenchymal cells in moderate and severe knee osteoarthritis is safe: a phase I /II study. J Orthop Surg Res. 2017;12(1):1–6.CrossRef
44.
Chahal J, Gómez-Aristizábal A, Shestopaloff K, Bhatt S, Chaboureau A, Fazio A, Chisholm J, Weston A, Chiovitti J, Keating A, Kapoor M, Ogilvie-Harris DJ, Syed KA, Gandhi R, Mahomed NN, Marshall KW, Sussman MS, Naraghi AM, Viswanathan S. Bone marrow mesenchymal stromal cell treatment in patients with osteoarthritis results in overall improvement in pain and symptoms and reduces synovial inflammation. Stem Cells Transl Med. 2019;8(8):746–57.PubMedPubMedCentralCrossRef
45.
Goncars V, Jakobsons E, Blums K, Briede I, Patetko L, Erglis K, Erglis M, Kalnberzs K, Muiznieks I, Erglis A. The comparison of knee osteoarthritis treatment with single-dose bone marrow-derived mononuclear cells vs. hyaluronic acid injections. Medicina. 2017;53(2):101–8.PubMedCrossRef
46.
Koh Y-G, Kwon O-R, Kim Y-S, Choi Y-J, Tak D-H. Adipose-derived mesenchymal stem cells with microfracture versus microfracture alone: 2-year follow-up of a prospective randomized trial. Arthrosc J Arthrosc Relat Surg. 2016;32(1):97–109.CrossRef
47.
Lu L, Dai C, Zhang Z, Du H, Li S, Ye P, Fu Q, Zhang L, Wu X, Dong Y, Song Y, Zhao D, Pang Y, Bao C. 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 Res Ther. 2019;10(1):1–10.CrossRef
48.
Pers Y-M, 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, on behalf of the ADIPOA Consortium. Adipose mesenchymal stromal cell-based therapy for severe osteoarthritis of the knee: a phase I dose-escalation trial. Stem Cells Transl Med. 2016;5(7):847–56.PubMedPubMedCentralCrossRef
49.
Spasovski D, Spasovski V, Baščarević Z, Stojiljković M, Vreća M, Anđelković M, Pavlović S. Intra-articular injection of autologous adipose-derived mesenchymal stem cells in the treatment of knee osteoarthritis. J Gene Med. 2018;20(1): e3002.CrossRef
50.
Song Y, Du H, Dai C, Zhang L, Li S, Hunter DJ, Lu L, Bao C. Human adipose-derived mesenchymal stem cells for osteoarthritis: a Pilot study with long-term follow-up and repeated injections. Regen Med. 2018;13(3):295–307.PubMedCrossRef
51.
Kim YS, Choi YJ, Lee SW, Kwon OR, Suh DS, Heo DB, Koh YG. Assessment of clinical and MRI outcomes after mesenchymal stem cell implantation in patients with knee osteoarthritis: a prospective study. Osteoarthr Cartil. 2016;24(2):237–45.CrossRef
52.
Koh Y-G, Choi Y-J. Infrapatellar fat pad-derived mesenchymal stem cell therapy for knee osteoarthritis. Knee. 2012;19(6):902–7.PubMedCrossRef
53.
Kim YS, Choi YJ, Suh DS, Heo DB, Kim YI, Ryu J-S, Koh YG. Mesenchymal stem cell implantation in osteoarthritic knees. Am J Sports Med. 2015;43(1):176–85.PubMedCrossRef
54.
Turajane T, Chaveewanakorn U, Fongsarun W, Aojanepong J, Papadopoulos KI. Avoidance of total knee arthroplasty in early osteoarthritis of the knee with intra-articular implantation of autologous activated peripheral blood stem cells versus hyaluronic acid: a randomized controlled tri al with differential effects of growth factor addition. Stem Cells Int. 2017;2017:1–10.CrossRef
55.
Yoshida S, Nishitani K, Yoshitomi H, Kuriyama S, Nakamura S, Fujii T, Saito M, Kobori Y, Murakami A, Murata K, Ito H, Ueno H, Matsuda S. Knee alignment correction by high tibial osteotomy reduces symptoms and synovial inflammation in knee osteoarthritis accompanied by macrophage phenotypic change from M1 to M2. Arthritis Rheumatol. 2023;75(6):950–60.PubMedCrossRef
56.
Wu ZP, Zhang P, Bai JZ, Liang Y, Chen PT, He JS, Wang JC. Comparison of navigated and conventional high tibial osteotomy for the treatment of osteoarthritic knees with varus deformity: a meta-analysis. Int J Surg. 2018;55:211–9.PubMedCrossRef
57.
Niemeyer P, Schmal H, Hauschild O, von Heyden J, Südkamp NP, Köstler W. Open-wedge osteotomy using an internal plate fixator in patients with medial-compartment gonarthritis and varus malalignment: 3-year results with regard to preoperative arthroscopic and radiographic findings. Arthrosc J Arthrosc Relat Surg. 2010;26(12):1607–16.CrossRef
58.
Hernigou P, Roussignol X, Flouzat-Lachaniette CH, Filippini P, Guissou I, Poignard A. Opening wedge tibial osteotomy for large varus deformity with Ceraver resorbable beta tricalcium phosphate wedges. Int Orthop. 2010;34(2):191–9.PubMedCrossRef
59.
Xie J, Lin J, Wei M, Teng Y, He Q, Yang G, Yang X. Sustained Akt signaling in articular chondrocytes causes osteoarthritis via oxidative stress-induced senescence in mice. Bone Res. 2019;7:23.PubMedPubMedCentralCrossRef
60.
Gao B, Lin X, Jing H, Fan J, Ji C, Jie Q, Zheng C, Wang D, Xu X, Hu Y, Lu W, Luo Z, Yang L. Local delivery of tetramethylpyrazine eliminates the senescent phenotype of bone marrow mesenchymal stromal cells and creates an anti-inflammatory and angiogenic environment in aging mice. Aging Cell. 2018;17(3): e12741.PubMedPubMedCentralCrossRef
61.
Yu B, Ma J, Li J, Wang D, Wang Z, Wang S. Mitochondrial phosphatase PGAM5 modulates cellular senescence by regulating mitochondrial dynamics. Nat Commun. 2020;11(1):2549.PubMedPubMedCentralCrossRef
62.
Upadhyay M, Milliner C, Bell BA, Bonilha VL. Oxidative stress in the retina and retinal pigment epithelium (RPE): role of aging, and DJ-1. Redox Biol. 2020;37: 101623.PubMedPubMedCentralCrossRef
63.
Ma L, Feng X, Wang K, Song Y, Luo R, Yang C. Dexamethasone promotes mesenchymal stem cell apoptosis and inhibits osteogenesis by disrupting mitochondrial dynamics. FEBS Open Bio. 2020;10(2):211–20.PubMedCrossRef
64.
Wang T, Liu X, He C. Glucocorticoid-induced autophagy and apoptosis in bone. Apoptosis. 2020;25(3–4):157–68.PubMedCrossRef
65.
Sun Y, Li W, Lu Z, Chen R, Ling J, Ran Q, Jilka RL, Chen XD. Rescuing replication and osteogenesis of aged mesenchymal stem cells by exposure to a young extracellular matrix. FASEB J. 2011;25(5):1474–85.PubMedPubMedCentralCrossRef
66.
Block TJ, Marinkovic M, Tran ON, Gonzalez AO, Marshall A, Dean DD, Chen XD. Restoring the quantity and quality of elderly human mesenchymal stem cells for autologous cell-based therapies. Stem Cell Res Ther. 2017;8(1):239.PubMedPubMedCentralCrossRef
Metadata
Title
Clinical outcomes of autologous adipose-derived mesenchymal stem cell combined with high tibial osteotomy for knee osteoarthritis are correlated with stem cell stemness and senescence
Authors
Houyi Sun
Haoxin Zhai
Kaifei Han
Heran Ma
Yi Tan
Shihao Li
Zhicheng Liu
Lei Cheng
Qunshan Lu
Libo Zhou
Peilai Liu
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2024
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-024-05814-3

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