Intra-articular injection of culture-expanded mesenchymal stem cells with or without addition of platelet-rich plasma is effective in decreasing pain and symptoms in knee osteoarthritis: a controlled, double-blind clinical trial
To compare the clinical and laboratory outcomes of intra-articular injections of culture-expanded bone-derived mesenchymal stem cells (MSCs) with or without platelet-rich plasma (PRP) to intra-articular corticosteroid injections for the treatment of knee osteoarthritis (OA).
Forty-seven patients with radiographic and symptomatic knee OA were randomized into three groups for intra-articular injections: autologous bone marrow-derived culture-expanded MSCs (n = 16); autologous bone marrow-derived culture-expanded MSCs + PRP (n = 14); and corticosteroid (n = 17). The outcomes were assessed by the Knee Injury and Osteoarthritis Outcome Score (KOOS) and range of motion (ROM) at baseline, 1, 2, 3, 6, 9 and 12 months and intra-articular cytokines analysis at baseline, 6 and 12 months postoperatively.
The three groups showed significant improvement in most KOOS domains and global score at 1st month and all domains and global score at 12-month follow-up (p < 0.05). At the 1st month, only the MSCs group showed significant differences in KOOS symptoms domain (p = 0.003). The MSCs and MSCs + PRP groups showed the highest percentage of improvement in most KOOS domains and global score compared to the corticosteroid group. All three groups showed a significant reduction in intra-articular levels of human interleukin-10 cytokine, from baseline to 12 months (p < 0.05).
An intra-articular injection of bone marrow-derived culture-expanded MSCs with or without the addiction of PRP is effective in improving the function and decreasing symptoms caused by knee OA at 12-month follow-up.
Level of evidence
KeywordsOsteoarthritis Mesenchymal stem cells Intra-articular injection Platelet-rich plasma
The authors would like to sincerely acknowledge ESHO Empresa de Serviços Hospitalares S.A and Keila Mara Cassiano.
RB, RB, MM, SR: conceptualized and designed the work; participated in the patient’s follow-up, acquisition, analysis, interpretation of data. RB, RA: drafted the work. VS, RFA, SR, JEM: revising it critically for important intellectual content; analyzed and interpreted the data. RFA, AB: biologists involved in platelet-rich plasma preparation protocol and procedures, and the culture-expanded MSCs procedures. RB: anesthesiologist physician involved in surgical procedures. RLR, JMO: senior biologists responsible for interpretation of the results and translation interpretation to clinical applications. All author approved the final version to be published.
The authors report no financial funding.
Compliance with ethical standards
Conflict of interest
No financial or non-financial competing interest exists for this manuscript. The manuscript was not influenced by personal or financial relationship with other people or organizations.
Comissão Nacional de Ética em Pesquisa (Brazilian National Ethics in Research Committee)–CONEP, under number 14878813.4.0000.5533.
- 1.Agung M, Ochi M, Yanada S, Adachi N, Izuta Y, Yamasaki T et al (2006) Mobilization of bone marrow-derived mesenchymal stem cells into the injured tissues after intraarticular injection and their contribution to tissue regeneration. Knee Surg Sports Traumatol Arthrosc 14:1307–1314CrossRefGoogle Scholar
- 5.Bastos R, Mathias M, Andrade R, Bastos R, Balduino A, Schott V et al (2018) Intra-articular injections of expanded mesenchymal stem cells with and without addition of platelet-rich plasma are safe and effective for knee osteoarthritis. Knee Surg Sports Traumatol Arthrosc 26:3342–3350CrossRefGoogle Scholar
- 7.Campbell KA, Saltzman BM, Mascarenhas R, Khair MM, Verma NN, Bach BR Jr et al (2015) Does intra-articular platelet-rich plasma injection provide clinically superior outcomes compared with other therapies in the treatment of knee osteoarthritis? A systematic review of overlapping meta-analyses. Arthroscopy 31:2213–2221CrossRefGoogle Scholar
- 8.Cole BJ, Karas V, Hussey K, Pilz K, Fortier LA (2017) Hyaluronic acid versus platelet-rich plasma: a prospective, double-blind randomized controlled trial comparing clinical outcomes and effects on intra-articular biology for the treatment of knee osteoarthritis. Am J Sports Med 45:339–346CrossRefGoogle Scholar
- 31.Lamo-Espinosa JM, Mora G, Blanco JF, Granero-Moltó F, Nuñez-Córdoba JM, Sánchez-Echenique C et al (2016) Intra-articular injection of two different doses of autologous bone marrow mesenchymal stem cells versus hyaluronic acid in the treatment of knee osteoarthritis: multicenter randomized controlled clinical trial (phase I/II). J Transl Med 14:246CrossRefGoogle Scholar
- 33.Lin KY, Yang CC, Hsu CJ, Yeh ML, Renn JH (2019) Intra-articular injection of platelet-rich plasma is superior to hyaluronic acid or saline solution in the treatment of mild to moderate knee osteoarthritis: a randomized, double-blind, triple-parallel, placebo-controlled clinical trial. Arthroscopy 35:106–117CrossRefGoogle Scholar
- 38.Ogura T, Ackermann J, Barbieri Mestriner A, Merkely G, Gomoll AH (2018) Minimal clinically important differences and substantial clinical benefit in patient-reported outcome measures after autologous chondrocyte implantation. Cartilage. https://doi.org/10.1177/19476035187998391947603518799839 CrossRefPubMedGoogle Scholar
- 48.Wong KL, Lee KBL, Tai BC, Law P, Lee EH, Hui JHP (2013) 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. Arthroscopy 29:2020–2028CrossRefGoogle Scholar