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

Dai, Wenli; Leng, Xi; Wang, Jian; Shi, Zhanjun; Cheng, Jin; Hu, Xiaoqing; Ao, Yingfang

doi:10.1016/j.arthro.2020.10.016

Cited by 30 publications

(64 citation statements)

References 90 publications

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“…Thus, Vasiliadis and Galanis 38 focused their systematic review and meta-analysis 8 on AD-MSCs (including eight controlled studies), showing clinical benefits in favor of MSCs, but not any measurable structural improvement. Another meta-analysis 39 analysed 13 randomized controlled trials (RCTs) involving MSCs (from any anatomical source) injections in knee OA. There was not any superiority of MSC treatments over placebo or HA, analysed as a percentage of responder patients who experienced minimum clinically important differences (MCDI) (for Visual Analogue Scale [VAS] and all The Western Ontario and MacMaster Universities Osteoarthritis Index [WOMAC] subscores).…”

Section: Overview Of Clinical Studies (Msc Products Delivery Route: Imentioning

confidence: 99%

Mesenchymal stromal cell products for intra-articular knee injections for conservative management of osteoarthritis

Andı́a

Maffulli

2021

Therapeutic Advances in Musculoskeletal

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Sports injuries and secondary joint problems, mainly of the knee, are common, especially in sports associated with high impact activities and/or torsional loading. The consequences can be career ending in elite athletes and reduce exercise activities in recreational people. Various cell products can be injected intra-articularly. First, fresh cellular mixtures can be prepared and injected in the same day, such as stromal vascular fraction of adipose tissue (SVF) and bone marrow concentrates (BMCs). Second, autologous mesenchymal stromal cells (MSCs) can be isolated from BMCs or SVF and, after several weeks of laboratory expansion, several millions of MSCs can be obtained for intra-articular injection. Finally, allogeneic MSCs from the bone marrow, adipose tissue or perinatal tissues of selected donors constitute an ‘off-the-shelf’ experimental treatment for injection delivery in patients with osteoarthritis of the knee. The perceived efficacy of all these products is based on the hypothesis of a paracrine mechanism of action: when living cells are delivered within the joint, they establish a molecular cross-talk with immune cells and local cell phenotypes, thereby modulating inflammation with subsequent modifications in the catabolic/degenerative milieu. Current clinical research examines whether injection delivery of MSCs translates into actual clinical benefits. Overall, clinical studies lack the quality needed to answer major research questions, including clinical and structural efficacy, optimal cell dose, and number of injections and specific protocol for cell delivery. Poor experimental designs are exacerbated by the diversity of patient phenotypes that hinder comparisons between treatments. Further understanding of disease pathology is paramount to develop potent function assays and understand whether the host tissue, the cell product or both should be primed before MSCs are injected intra-articularly.

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Section: Overview Of Clinical Studies (Msc Products Delivery Route: Imentioning

confidence: 99%

Mesenchymal stromal cell products for intra-articular knee injections for conservative management of osteoarthritis

Andı́a

Maffulli

2021

Therapeutic Advances in Musculoskeletal

View full text Add to dashboard Cite

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“…We read with anticipation the recently published review by Dai et al, 1 "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." We appreciated the authors' efforts to compile a comprehensive review and meta-analysis of Level I studies, which contrast with prior reviews of mesenchymal stromal cell (MSC) injections that have included lowerquality research.…”

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confidence: 99%

“…Dai et al 1 grouped together studies describing the use of culture-expanded bone marrow MSCs, cultureexpanded adipose MSCs, stromal vascular fraction (SVF), culture-expanded placental MSCs, cultureexpanded umbilical cord MSCs, and bone marrow concentrate (BMC) with platelet-poor plasma and analyzed them as if they were a uniform therapy with associated uniform efficacy. Outside of involving the use of some type of MSC, the therapies are vastly different and not comparable.…”

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confidence: 99%

“…The control groups that the authors included as "placebos" included normal saline solution, hyaluronic acid, conditioned media, plasma, Ringer lactate, and conservative care. 1 Indeed, only 4 of the 13 studies included for review used a true placebo comparator (normal saline solution), whereas 5 studies used hyaluronic acid, a common injection therapy for knee osteoarthritis, in their comparison group. Furthermore, 2 studies used uncommon therapies, including Plasma-Lyte A (serum, albumin, and dimethyl sulfoxide) (Baxter) and conditioned cell culture media, the latter of which contains exosomes and is already in use in early clinical trials as a knee osteoarthritis therapeutic agent.…”

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confidence: 99%

“…6,7 Collectively, the mixture of studies that used control groups with varying amounts of efficacy, rather than true placebo treatments, could have had only a single result: to bias the meta-analysis result toward the null. We are surprised the article by Dai et al 1 passed the peer-review process given the improper inclusion of studies using non-placebo and potentially therapeutic comparison groups. Moreover, it is surprising that the authors did not include at least 1 positive randomized controlled trial that fits with the other included studies.…”

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confidence: 99%

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