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

Abstract

Background:Osteoarthritis is most prevalent in the knee and drives the growing incidence of total knee arthroplasty. There is a need to explore non-surgical treatment options to increase the portfolio of alternatives available. The study aimed to determine the clinical response to an autologous bone marrow aspirate concentrate (BMAC) and platelet-rich plasma (PRP) intra-articular injection compared to an active comparator. Methods:The study was a prospective, single-blinded, randomized controlled pilot study. Participants with diagnosed knee osteoarthritis were allocated to one of two treatment groups to receive a BMAC injection immediately followed by a PRP injection or a single injection of Gel-One ® crosslinked hyaluronate (HA). Outcomes were assessed at 3, 6, and 12 months post-treatment. Results:Significant improvements were observed in both treatment groups for all Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales with the exception of the symptoms assessment at 12 months in the HA group. BMAC KOOS scores peaked at 12 months, while HA KOOS scores generally peaked at 6 months. The gap in mean scores at 12 months in favor of the BMAC group did not reach statistical significance. Secondary outcomes included a greater reduction in pain at 12 months in the BMAC group (-3.13 points; 95% CI: -3.96, -3.29) compared to the HA group (-1.56 points; 95% CI: -2.59, -0.53; p= 0.02) via the numeric pain rating scale. Conclusions:Results demonstrate that both treatment groups experienced clinically and statistically significant improvement across the KOOS subscales. While BMAC has shown promise in the treatment of knee OA, there is a need for multi-center investigations with larger sample sizes, an extended follow-up, and placebo-based control. ClinicalTrials.gov Identifier: NCT02958267 progressing to a surgical intervention in cases where non-surgical treatment fails to relieve the underlying symptoms [7][8][9] . The accepted option for knee OA when non-surgical options fail is total knee arthroplasty (TKA). The prevalence of knee arthroplasty increased 300% in the United States from 1990 to 2010 [10] . Considering the aging demographic in the United States, the demand for primary TKA is expected to increase by another twoto seven-folds by 2030 with associated costs increasing exponentially [11,12] . The growing costs [13] , added to the risk of complications associated with TKA [14] , demonstrates the importance of evaluating lower risk and lower cost options to manage the condition with intent to delay the need for surgical intervention or avoid surgical intervention in a subset of the population.Conservative treatment options such as physical exercise and weight loss are recommended as an initial option to OA. [7][8][9] Pain associated with knee OA is often treated with non-steroidal

Does vehicle-based delivery of mesenchymal stromal cells give superior results in knee osteoarthritis? Meta-analysis of randomized controlled trials

“…PRISMA flow diagram of study selection is given in Figure 1. 10/21 studies 25,29,31,[33][34][35][36]39,40,42 utilized vehicle-based delivery of MSCs of which PRP and HA were the commonly utilized delivery methods.…”

“…9/21 studies 23,27,28,30,32,[37][38][39][40][41] utilized MSC from adipose tissue, of which 1 used an allogenic source and the rest 8 studies utilized autogenous source of MSCs. 12/21 studies [23][24][25][26]29,31,[33][34][35][36]42,43 utilized MSC from bone marrow, of which 2 used allogenic sources, and the rest 10 studies utilized autogenous sources of MSCs. There was also no uniformity among the included studies for the outcome measures utilized.…”

Is Culture Expansion Necessary in Autologous Mesenchymal Stromal Cell Therapy to Obtain Superior Results in the Management of Knee Osteoarthritis?—Meta-Analysis of Randomized Controlled Trials

“…Hence, we pooled the results of all the included studies utilizing autologous culture expanded MSCs into one group and non-cultured MSCs into another group, and performed a combined comparative quantitative analysis. We included 17 included studies [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ] with 767 patients for meta-analysis. A PRISMA flow diagram of study selection is given in Figure 1 .…”

“…Overall, 9/17 studies [ 21 , 22 , 24 , 25 , 26 , 27 , 28 , 30 , 35 ] utilized culture expanded MSCs, of which three studies used adipose-derived MSCs [ 21 , 25 , 30 ], and the remaining six studies utilized MSCs of bone marrow origin. Overall, 8/17 studies [ 19 , 20 , 23 , 29 , 31 , 32 , 33 , 34 ] utilized non-cultured MSCs, of which four studies utilized MSCs of adipose origin [ 23 , 29 , 31 , 32 , 33 ], three studies utilized MSCs of bone marrow origin [ 19 , 20 , 34 ], and one study [ 19 ] used both bone marrow and adipose tissue as their MSC source. All of the studies using culture expanded MSCs used cells before the fourth passage.…”

“…We analyzed two studies [ 21 , 27 ], and three studies [ 19 , 32 , 34 ] reporting the KOOS score at 12 months using culture expanded and non-cultured MSCs, respectively. There was a significant heterogeneity observed between the included studies.…”