Safety and efficacy of placental mesenchymal stromal cells-derived extracellular vesicles in knee osteoarthritis: a randomized, triple-blind, placebo-controlled clinical trial.
Humans
Osteoarthritis, Knee
/ therapy
Female
Extracellular Vesicles
/ transplantation
Middle Aged
Male
Placenta
/ diagnostic imaging
Pregnancy
Treatment Outcome
Mesenchymal Stem Cell Transplantation
/ methods
Mesenchymal Stem Cells
Injections, Intra-Articular
Aged
Magnetic Resonance Imaging
Double-Blind Method
Extracellular vesicles
Knee osteoarthritis
MRI
Journal
BMC musculoskeletal disorders
ISSN: 1471-2474
Titre abrégé: BMC Musculoskelet Disord
Pays: England
ID NLM: 100968565
Informations de publication
Date de publication:
28 Oct 2024
28 Oct 2024
Historique:
received:
10
05
2024
accepted:
18
10
2024
medline:
28
10
2024
pubmed:
28
10
2024
entrez:
28
10
2024
Statut:
epublish
Résumé
Knee osteoarthritis causes pain and disability in many people worldwide, for which no definitive treatment has yet been proposed. In this study, we investigated the safety and efficacy of placental mesenchymal stromal cells-derived extracellular vesicles in patients with knee osteoarthritis. This triple-blind, randomized clinical trial included patients suffering from bilateral knee osteoarthritis with grade 2 or 3. The knees of each patient were randomized to intervention and control. For the intervention knee, 5 cc of placental mesenchymal stromal cells-derived extracellular vesicles were injected, and for the control knee, 5 cc of normal saline was injected. The patients' symptoms were evaluated before the intervention and 2 and 6 months after the intervention using VAS, WOMAC questionnaire, and Lequesne index. MRI was performed before the intervention and 6 months after the intervention to evaluate retropatellar and tibiofemoral cartilage volume, medial and lateral meniscal disintegrity, ACL injury, and effusion-synovitis. 62 knees (31 patients) were enrolled in this study. There were 31 knees as intervention and 31 knees as control. Finally, the data of 58 knees (29 patients) were analyzed, including 28 women and 1 man. The mean age of the patients was 55.38 ± 6.07 years. No statistically significant difference was detected between the two groups in clinical outcomes (including VAS, WOMAC, and Lequesne scores) before treatment and 2 and 6 months after treatment. Also, no statistically significant difference was detected between the two groups in MRI findings before treatment and 6 months after treatment. No systemic complications or severe local reactions occurred in the patients. A single intra-articular injection of placental mesenchymal stromal cells-derived extracellular vesicles (5 cc, 7 × 10
Sections du résumé
BACKGROUND
BACKGROUND
Knee osteoarthritis causes pain and disability in many people worldwide, for which no definitive treatment has yet been proposed. In this study, we investigated the safety and efficacy of placental mesenchymal stromal cells-derived extracellular vesicles in patients with knee osteoarthritis.
METHODS
METHODS
This triple-blind, randomized clinical trial included patients suffering from bilateral knee osteoarthritis with grade 2 or 3. The knees of each patient were randomized to intervention and control. For the intervention knee, 5 cc of placental mesenchymal stromal cells-derived extracellular vesicles were injected, and for the control knee, 5 cc of normal saline was injected. The patients' symptoms were evaluated before the intervention and 2 and 6 months after the intervention using VAS, WOMAC questionnaire, and Lequesne index. MRI was performed before the intervention and 6 months after the intervention to evaluate retropatellar and tibiofemoral cartilage volume, medial and lateral meniscal disintegrity, ACL injury, and effusion-synovitis.
RESULTS
RESULTS
62 knees (31 patients) were enrolled in this study. There were 31 knees as intervention and 31 knees as control. Finally, the data of 58 knees (29 patients) were analyzed, including 28 women and 1 man. The mean age of the patients was 55.38 ± 6.07 years. No statistically significant difference was detected between the two groups in clinical outcomes (including VAS, WOMAC, and Lequesne scores) before treatment and 2 and 6 months after treatment. Also, no statistically significant difference was detected between the two groups in MRI findings before treatment and 6 months after treatment. No systemic complications or severe local reactions occurred in the patients.
CONCLUSION
CONCLUSIONS
A single intra-articular injection of placental mesenchymal stromal cells-derived extracellular vesicles (5 cc, 7 × 10
Identifiants
pubmed: 39465400
doi: 10.1186/s12891-024-07979-w
pii: 10.1186/s12891-024-07979-w
doi:
Types de publication
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
856Informations de copyright
© 2024. The Author(s).
Références
Felson DT. The epidemiology of knee osteoarthritis: results from the Framingham Osteoarthritis Study. Semin Arthritis Rheum. 1990;20:42–50.
doi: 10.1016/0049-0172(90)90046-I
pubmed: 2287948
Wallace IJ, Worthington S, Felson DT, Jurmain RD, Wren KT, Maijanen H, et al. Knee osteoarthritis has doubled in prevalence since the mid-20th century. PNAS. 2017;114(35):9332–6.
doi: 10.1073/pnas.1703856114
pubmed: 28808025
pmcid: 5584421
Raeissadat SA, Ghazi Hosseini P, Bahrami MH, Salman Roghani R, Fathi M, Gharooee Ahangar A, et al. The comparison effects of intra-articular injection of platelet Rich plasma (PRP), plasma Rich in Growth factor (PRGF), Hyaluronic Acid (HA), and ozone in knee osteoarthritis; a one year randomized clinical trial. BMC Musculoskelet Disord. 2021;22(1):134.
doi: 10.1186/s12891-021-04017-x
pubmed: 33536010
pmcid: 7860007
Steinmetz JD, Culbreth GT, Haile LM, Rafferty Q, Lo J, Fukutaki KG, et al. Global, regional, and national burden of osteoarthritis, 1990–2020 and projections to 2050: a systematic analysis for the global burden of Disease Study 2021. Lancet Rheumatol. 2023;5(9):e508–22.
doi: 10.1016/S2665-9913(23)00163-7
Raeissadat SA, Ghorbani E, Sanei Taheri M, Soleimani R, Rayegani SM, Babaee M, et al. MRI changes after platelet Rich plasma injection in knee osteoarthritis (Randomized Clinical Trial). J Pain Res. 2020;13:65–73.
doi: 10.2147/JPR.S204788
pubmed: 32021396
pmcid: 6959502
Bahrami MH, Raeissadat SA, Cheraghi M, Rahimi Dehgolan S, Ebrahimpour A. Efficacy of single high-molecular-weight versus triple low-molecular-weight hyaluronic acid intra-articular injection among knee osteoarthritis patients. BMC Musculoskelet Disord. 2020;21(1):550.
doi: 10.1186/s12891-020-03577-8
pubmed: 32799851
pmcid: 7429877
Raeissadat SA, Rayegani SM, Sedighipour L, Bossaghzade Z, Abdollahzadeh MH, Nikray R, et al. The efficacy of electromyographic biofeedback on pain, function, and maximal thickness of vastus medialis oblique muscle in patients with knee osteoarthritis: a randomized clinical trial. J Pain Res. 2018;11:2781–9.
doi: 10.2147/JPR.S169613
pubmed: 30519081
pmcid: 6235326
Song Y, Jorgensen C. Mesenchymal stromal cells in Osteoarthritis: evidence for Structural Benefit and Cartilage Repair. Biomedicines. 2022;10(6):1278.
doi: 10.3390/biomedicines10061278
pubmed: 35740299
pmcid: 9219878
Hass R, Kasper C, Böhm S, Jacobs R. Different populations and sources of human mesenchymal stem cells (MSC): a comparison of adult and neonatal tissue-derived MSC. Cell Communication Signal. 2011;9:12.
doi: 10.1186/1478-811X-9-12
Khalifeh Soltani S, Forogh B, Ahmadbeigi N, Hadizadeh Kharazi H, Fallahzadeh K, Kashani L, et al. Safety and efficacy of allogenic placental mesenchymal stem cells for treating knee osteoarthritis: a pilot study. Cytotherapy. 2019;21(1):54–63.
doi: 10.1016/j.jcyt.2018.11.003
pubmed: 30522806
Yuan S, Li G, Zhang J, Chen X, Su J, Zhou F. Mesenchymal stromal cells-derived extracellular vesicles as potential treatments for Osteoarthritis. Pharmaceutics. 2023;15(7):1814.
doi: 10.3390/pharmaceutics15071814
pubmed: 37514001
pmcid: 10385170
Zhuang Y, Jiang S, Yuan C, Lin K. The potential therapeutic role of extracellular vesicles in osteoarthritis. Front Bioeng Biotechnol. 2022;10:1022368.
doi: 10.3389/fbioe.2022.1022368
pubmed: 36185451
pmcid: 9523151
Ni Z, Zhou S, Li S, Kuang L, Chen H, Luo X, et al. Exosomes: roles and therapeutic potential in osteoarthritis. Bone Res. 2020;8:25.
doi: 10.1038/s41413-020-0100-9
pubmed: 32596023
pmcid: 7305215
D’Arrigo D, Roffi A, Cucchiarini M, Moretti M, Candrian C, Filardo G. Secretome and Extracellular vesicles as New Biological therapies for knee osteoarthritis: a systematic review. J Clin Med. 2019;8(11):1867.
doi: 10.3390/jcm8111867
pubmed: 31689923
pmcid: 6912212
Kim KH, Jo JH, Cho HJ, Park TS, Kim TM. Therapeutic potential of stem cell-derived extracellular vesicles in osteoarthritis: preclinical study findings. Lab Anim Res. 2020;36:10.
doi: 10.1186/s42826-020-00043-3
pubmed: 32322556
pmcid: 7160998
Emadedin M, Labibzadeh N, Ghorbani Liastani M, Karimi A, Jaroughi N, Bolurieh T, et al. Intra-articular implantation of autologous bone marrow-derived mesenchymal stromal cells to treat knee osteoarthritis: a randomized, triple-blind, placebo-controlled phase 1/2 clinical trial. Cytotherapy. 2018;20(10):1238–46.
doi: 10.1016/j.jcyt.2018.08.005
pubmed: 30318332
Bao X, Tan JW, Flyzik M, Ma XC, Liu H, Liu HY. Effect of therapeutic exercise on knee osteoarthritis after intra-articular injection of botulinum toxin type A, hyaluronate or saline: a randomized controlled trial. J Rehabil Med. 2018;50(6):534–41.
doi: 10.2340/16501977-2340
pubmed: 29664106
Raeissadat SA, Rayegani SM, Gharooee Ahangar A, Hassan Abadi P, Mojgani P, Gharooi Ahangar O. Efficacy of Intra-articular Injection of a Newly Developed Plasma Rich in Growth Factor (PRGF) Versus Hyaluronic Acid on Pain and Function of Patients with Knee Osteoarthritis: A Single-Blinded Randomized Clinical Trial. Clinical Medicine Insights: Arthritis and Musculoskeletal Disorders. 2017; 10:1179544117733452.
Guermazi M, Poiraudeau S, Yahia M, Mezganni M, Fermanian J, Habib Elleuch M, et al. Translation, adaptation and validation of the Western Ontario and McMaster universities osteoarthritis index (WOMAC) for an arab population: the Sfax modified WOMAC. Osteoarthr Cartil. 2004;12(6):459–68.
doi: 10.1016/j.joca.2004.02.006
Peterfy CG, Guermazi A, Zaim S, Tirman PF, Miaux Y, White D, et al. Whole-organ magnetic resonance imaging score (WORMS) of the knee in osteoarthritis. Osteoarthr Cartil. 2004;12(3):177–90.
doi: 10.1016/j.joca.2003.11.003
Hunter DJ, Guermazi A, Lo GH, Grainger AJ, Conaghan PG, Boudreau RM, et al. Evolution of semi-quantitative whole joint assessment of knee OA: MOAKS (MRI osteoarthritis knee score). Osteoarthr Cartil. 2011;19(8):990–1002.
doi: 10.1016/j.joca.2011.05.004
Sariboyaci AE. A phase II trial to investigate clinical efficacy of autologous synovial fluid mesenchymal stem cell-derived exosome application in patients with degenerative Meniscal Injury. 2022; [Available from: ClinicalTrials.gov].
Espinoza FA, Phase I. Study Aiming to Assess Safety and Efficacy of a Single Intra-articular Injection of MSC-derived Exosomes (CelliStem
Hashemian SR, Aliannejad R, Zarrabi M, Soleimani M, Vosough M, Hosseini SE, et al. Mesenchymal stem cells derived from perinatal tissues for treatment of critically ill COVID-19 induced ARDS patients: a case series. Stem Cell Res Ther. 2021;12(1):91.
doi: 10.1186/s13287-021-02165-4
pubmed: 33514427
pmcid: 7844804
Jahedi Zargar M, Heidari Keshel S, Kaviani S, Zahraei M, Izadyari Aghmiuni A, Savadkoohi AA, et al. Safety and efficacy of placental mesenchymal stem cell-derived extracellular vesicle in severe COVID-19 patients: phase I & II clinical trials. Anat Sci. 2022;19(2):79–88.
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 Translational Med. 2019;8(6):504–11.
doi: 10.1002/sctm.18-0122
Lu L, Dai C, Zhang Z, Du H, Li S, Ye P, et al. 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):143.
doi: 10.1186/s13287-019-1248-3
pubmed: 31113476
pmcid: 6528322
Matas J, Orrego M, Amenabar D, Infante C, Tapia-Limonchi R, Cadiz MI, 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 Translational Med. 2019;8(3):215–24.
doi: 10.1002/sctm.18-0053
Dai W, Leng X, Wang J, Shi Z, Cheng J, Hu X, Ao Y. Intra-articular mesenchymal stromal cell injections are no different from placebo in the treatment of knee osteoarthritis: a systematic review and Meta-analysis of Randomized controlled trials. Arthroscopy. 2021;37(1):340–58.
doi: 10.1016/j.arthro.2020.10.016
pubmed: 33098949