Mesenchymal Stem Cells Secretome and Osteoarthritis: A State of The Art
Abstract
No agreed cure or procedure can prevent the damage caused by OA. Current treatments such as physiotherapy, anti-inflammatory drugs, and viscous supplements are symptomatic and are aimed solely at pain relief. Mesenchymal stem cells, on the other hand, refer to a population of cells with immunomodulatory and homing properties. Recent studies have shown that stem cells produce secretomes with tissue regeneration, immunomodulation, anti-inflammatory, and anti-apoptotic capacities.
Secretomes in conditioned media produced by mesenchymal stem cells can stimulate the repair of cartilage defects. There are many evidence from many studies both in vitro and in vivo which provide potential results. The improvement can be seen from the morphology, in the form of thickening of the cartilage, an increase in the number of chondrocyte cells, regular joint surfaces, and histologically it can be seen that there is an improvement in the joint cartilage matrix. Likewise, histological studies using immunohistochemistry also showed an increase in the expression of TGF-β, SOX-9, aggrecan, and type II collagen which is a pathway for the formation of hyaline cartilage repair. Not only improvement, other studies have also shown that the secretome can provide a protective effect on joint cartilage by increasing the expression of the COL2A1 gene which functions to form collagen matrix components and reduces apoptosis in chondrocyte cells.
Secretomes produced by mesenchymal stem cells can stimulate the repair of cartilage damage, anti-inflammatory, immunomodulator, angiogenesis, and anti-apoptotic abilities from their cytokines and extra vesicles contains miRNA. MSCs secretomes are more stable and provide simpler manufacturing than MSCs themselves.
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Aspden RM, Saunders FR. Osteoarthritis as an organ disease: From the cradle to the grave. Eur Cells Mater. 2019;37:74-87. doi:10.22203/eCM.v037a06
Ilham Wildan Ahmad1*, Lita Diah Rahmawati 2 THW. Demographic Profile, Clinical and Analysis of Osteoarthritis Patients in Surabaya Ilham. Biomol Heal Sci J. 2018;1(1):52. doi:10.20473/bhsj.v1i1.8209
Koentjoro SL. Hubungan antara Indeks Masa tubuh (IMT) dengan Derajat Osteoartritis Lutut Menurut Kellgren dan Lawrence. Fak Kedokt Univ Diponegoro. Published online 2010:1-20.
Dewi S, Kalim H, Alwi I. Rekomendasi IRA Untuk Diagnosis Dan Penatalaksanaan Osteoartritis.; 2014.
Bousnaki M, Bakopoulou A, Kritis A, Koidis P. The Efficacy of Stem Cells Secretome Application in Osteoarthritis: A Systematic Review of In Vivo Studies. Stem Cell Rev Reports. 2020;16(6):1222-1241. doi:10.1007/s12015-020-09980-x
Lee WY wai, Wang B. Cartilage repair by mesenchymal stem cells: Clinical trial update and perspectives. J Orthop Transl. 2017;9:76-88. doi:10.1016/j.jot.2017.03.005
Caplan AI. Mesenchymal Stem Cells : Time to Change the Name ! STEMCELLS Transl Med 2017. 2017;(6):1445-1451.
Arrigoni C, D’Arrigo D, Rossella V, Candrian C, Albertini V, Moretti M. Umbilical Cord MSCs and Their Secretome in the Therapy of Arthritic Diseases: A Research and Industrial Perspective. Cells. 2020;9(6):1-20. doi:10.3390/cells9061343
Centeno CJ, Faulkner S. The Use of Mesenchymal Stem Cells in Orthopedics : Review of the Literature , Current Research , and Regulatory Landscape. J Am physicians Surg. 2011;16(2):38-44.
Colombini A, Perucca Orfei C, Kouroupis D, et al. Mesenchymal stem cells in the treatment of articular cartilage degeneration: New biological insights for an old-timer cell. Cytotherapy. 2019;21(12):1179-1197. doi:10.1016/j.jcyt.2019.10.004
Han Y, Li X, Zhang Y, Han Y, Chang F, Ding J. Mesenchymal stem cells for regenerative medicine. Cells. 2019;8(8). doi:10.3390/cells8080886
Hwang JJ, Rim YA, Nam Y, Ju JH. Recent Developments in Clinical Applications of Mesenchymal Stem Cells in the Treatment of Rheumatoid Arthritis and Osteoarthritis. Front Immunol. 2021;12(March). doi:10.3389/fimmu.2021.631291
Pittenger MF, Discher DE, Péault BM, Phinney DG, Hare JM, Caplan AI. Mesenchymal stem cell perspective: cell biology to clinical progress. npj Regen Med. 2019;4(1). doi:10.1038/s41536-019-0083-6
Fan XL, Zhang Y, Li X, Fu QL. Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy. Cell Mol Life Sci. 2020;77(14):2771-2794. doi:10.1007/s00018-020-03454-6
Kim JW, Kim SY, Park SY, et al. Mesenchymal progenitor cells in the human umbilical cord. Ann Hematol. 2004;83(12):733-738. doi:10.1007/s00277-004-0918-z
Nagamura-Inoue T. Umbilical cord-derived mesenchymal stem cells: Their advantages and potential clinical utility. World J Stem Cells. 2014;6(2):195. doi:10.4252/wjsc.v6.i2.195
Chen JY, Mou XZ, Du XC, Xiang C. Comparative analysis of biological characteristics of adult mesenchymal stem cells with different tissue origins. Asian Pac J Trop Med. 2015;8(9):739-746. doi:10.1016/j.apjtm.2015.07.022
Kim JH, Jo CH, Kim HR, Hwang Y Il. Comparison of immunological characteristics of mesenchymal stem cells from the periodontal ligament, umbilical cord, and adipose tissue. Stem Cells Int. 2018;2018. doi:10.1155/2018/8429042
Marmotti A, Mattia S, Castoldi F, et al. Allogeneic Umbilical Cord-Derived Mesenchymal Stem Cells as a Potential Source for Cartilage and Bone Regeneration: An in Vitro Study. Stem Cells Int. 2017;2017. doi:10.1155/2017/1732094
Nepali S, Park M, Lew H, Kim O. Comparative Analysis of Human Adipose-Derived Mesenchymal Stem Cells from Orbital and Abdominal Fat. Stem Cells Int. 2018;2018. doi:10.1155/2018/3932615
Li N, Gao J, Mi L, et al. Synovial membrane mesenchymal stem cells: Past life, current situation, and application in bone and joint diseases. Stem Cell Res Ther. 2020;11(1):1-12. doi:10.1186/s13287-020-01885-3
Ni Z, Zhou S, Li S, et al. Exosomes: roles and therapeutic potential in osteoarthritis. Bone Res. 2020;8(1). doi:10.1038/s41413-020-0100-9
Li JJ, Hosseini-Beheshti E, Grau GE, Zreiqat H, Little CB. Stem cell-derived extracellular vesicles for treating joint injury and osteoarthritis. Nanomaterials. 2019;9(2):1-21. doi:10.3390/nano9020261
Driscoll J, Patel T. The mesenchymal stem cell secretome as an acellular regenerative therapy for liver disease. J Gastroenterol. 2019;54(9):763-773. doi:10.1007/s00535-019-01599-1
Soetjahjo B, Hidayat M, Sujuti H, Fibrianto YH. The significant effect of conditioned medium of umbilical cord mesenchymal stem cells in histological improvement of cartilage defect in Wistar rats. Turkish J Immunol. 2018;6(2):57-64. doi:10.25002/tji.2018.682
Soetjahjo B, Hidayat M, Sujuti H, Fibrianto Y. Immunohistochemistry Evaluation of TGF-β1, SOX-9, Type II Collagen and Aggrecan in Cartilage Lesions Treated with Conditioned Medium of Umbilical Cord Mesencyhmal Stem Cells in Wistar Mice (Rattus novergicus). J Trop Life Sci. 2018;8(1):21-27. doi:10.11594/jtls.08.01.05
Chen W, Sun Y, Gu X, et al. Conditioned medium of mesenchymal stem cells delays osteoarthritis progression in a rat model by protecting subchondral bone, maintaining matrix homeostasis, and enhancing autophagy. J Tissue Eng Regen Med. 2019;13(9):1618-1628. doi:10.1002/term.2916
Science EM, Sciences M, Hospital SV. R EGENERATIVE M EDICINE Thrombospondin-2 Secreted by Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Promotes Chondrogenic Differentiation. Published online 2013:2136-2148. doi:10.1002/May
Wu X, Wang Y, Xiao Y, Crawford R, Mao X, Prasadam I. Extracellular vesicles: Potential role in osteoarthritis regenerative medicine. J Orthop Transl. 2020;21(April 2019):73-80. doi:10.1016/j.jot.2019.10.012
Zhou Q, Cai Y, Jiang Y, Lin X. Exosomes in osteoarthritis and cartilage injury: Advanced development and potential therapeutic strategies. Int J Biol Sci. 2020;16(11):1811-1820. doi:10.7150/ijbs.41637
Kim YS, Choi YJ, Koh YG. Mesenchymal Stem Cell Implantation in Knee Osteoarthritis: An Assessment of the Factors Influencing Clinical Outcomes. Am J Sports Med. 2015;43(9):2293-2301. doi:10.1177/0363546515588317
Shapiro SA, Kazmerchak SE, Heckman MG, Zubair AC, O’Connor MI. A Prospective, Single-Blind, Placebo-Controlled Trial of Bone Marrow Aspirate Concentrate for Knee Osteoarthritis. Am J Sports Med. 2017;45(1):82-90. doi:10.1177/0363546516662455
Matas J, Orrego M, Amenabar D, et al. Umbilical Cord-Derived Mesenchymal Stromal Cells (MSCs) for Knee Osteoarthritis: Repeated MSC Dosing Is Superior to a Single MSC Dose and to Hyaluronic Acid in a Controlled Randomized Phase I/II Trial. Stem Cells Transl Med. 2019;8(3):215-224. doi:10.1002/sctm.18-0053
Pers Y-M, Rackwitz L, Ferreira R, et al. 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):847-856. http://stemcellstm.alphamedpress.org/cgi/doi/10.5966/sctm.2015-0245
Freitag J, Bates D, Wickham J, et al. Adipose-derived mesenchymal stem cell therapy in the treatment of knee osteoarthritis: A randomized controlled trial. Regen Med. 2019;14(3):213-230. doi:10.2217/rme-2018-0161
Lee WS, Kim HJ, Kim K Il, 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):504-511. doi:10.1002/sctm.18-0122
DOI: https://doi.org/10.46355/hipknee.v3i2.133
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