A systematic review of the treatment of knee osteoarthritis with intraarticular injection of mesenchymal stem cells

Abstract

Background: A wide array of treatment, both surgical and nonsurgical, exists for osteoarthritis (OA) of the knee. Injectable stem-cell therapy represents a minimally invasive and potentially efficacious treatment; however, there have been no level I studies conducted on this specific application of stem-cell therapy. The purpose of our review was to analyze, report, and summarize current topical data. Methods: A systematic review of the treatment of human knee OA with mesenchymal stem cells (MSCs) was performed by searching PubMed/Medline and Google Scholar. Non-human studies and studies involving additional procedures were excluded. Authors reviewed the studies individually, with the primary author deciding on inclusion. Results: Our search ultimately returned 10 studies that met the inclusion criteria. Nine of the ten studies used cultured autologous MSCs, five from bone marrow, three from subcutaneous fat, and one from peripheral blood. The remaining study used allogenic bone marrow MSCs. Radiographic analysis of cartilage quality via MRI T2 mapping showed increased type II collagen production in five studies. Outcome scores consistently showed pain reduction and improved function. No study reported significant adverse events related to stem-cell therapy. Conclusions: Current human studies evaluating the use of injected MSCs for knee OA demonstrated consistent improvement across several outcome scores, with no significant adverse findings. Level of Evidence: Level IV, systematic review of Level II-IV trials and studies.

A Single-Blinded Randomized Controlled Trial of Mesenchymal Stem Cell Therapy for the Treatment of Osteoarthritis of the Knee with Active Control

“…MSCs can be obtained by way of bone marrow aspirate concentrate (BMAC) or adipose tissue. Available systematic reviews and/or meta-analyses generally demonstrate early benefits in the application of orthobiologics for OA [22][23][24][25] . Studies specifically evaluating IA application of BMAC [26][27][28] or adipose-derived MSCs [29,30] have demonstrated consistent improvement in pain and function at follow-up time points ranging from 6-24 months.…”

Methodological Quality and Risk of Bias of Systematic Reviews and Meta-Analyses on Stem Cells for Knee Osteoarthritis: A Cross-Sectional Survey

“…The full-texts of the remaining 71 references were screened. Finally, 22 references were included [11][12][13][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45]. The reference inclusion and exclusion process is shown in gure 1 (Flow diagram of study retrieval and selection).…”

“…The publication year ranged from 2015 to 2021. In terms of the country of the rst author, 50% (n=11) of the publications were from China [13, 27-29, 35, 37, 38, 41-44], 18.18% (n=4) from Korea [12,32,33,40], 9.09% (n=2) from US [31,36], while 4.55% (n=1) from Netherlands [11], Japan [30], Germany [34], India [39] and Singapore [45], respectively. Regarding the study type, 54.55% (n=12) of SRs/MAs only contained RCTs [12,13,29,[35][36][37][38][39][40][41][42]44], while the remaining SRs/MAs involved both RCTs and non-RCTs [11, 27, 28, 30-34, 43, 45].…”

“…Among them, one used the Downs and Black scale but did not evaluate the selective reporting bias [30], whereas the other adopted the modi ed Newcastle-Ottawa scale for non-RCTs and did not evaluate the selective reporting bias [43]. The remaining 45.45% (n=10) of the enrolled SRs/MAs were rated as "No", including two adopting the Jadad scale for RCTs [29,38], ve not reporting the signi cant bias results [11,27,28,32,33], and three not reporting the tool used [31,34,36].…”

“…Three SRs/MAs only included RCTs, but did not correct the existing heterogeneity [12,29,37]. The remaining 22.73% (n=5) of the SRs/MAs were qualitative studies without data combination [11,31,33,34, 36] (rated as "No MAs conducted").…”