Effectiveness of AD-MSCs injections for the treatment of knee osteoarthritis: Analysis of the current literature

Vasiliadis, Angelo V.; Galanis, Nikiforos

doi:10.46582/jsrm.1601002

Cited by 7 publications

(3 citation statements)

References 16 publications

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“…MRI and radiographic evaluations are currently the most common option applied in the clinical setting and showed the lowest ability in detecting the effects of the applied treatments. This confirms the limits of the imaging evaluations already documented in the clinical practice, where there is a poor correlation between clinical outcome and imaging findings [ 71 ]. In this light, the limits of imaging techniques should be considered with caution to draw conclusions on treatment effectiveness in the clinical practice, as more disease-modifying effects have been found in the literature using other methods rather than MRI and radiographs, as underlined by the tissue and biomarker analysis in the animal models.…”

Section: Discussionsupporting

confidence: 83%

Cell-based therapies have disease-modifying effects on osteoarthritis in animal models. A systematic review by the ESSKA Orthobiologic Initiative. Part 1: adipose tissue-derived cell-based injectable therapies

Orfei

Boffa

Sourugeon

et al. 2022

Knee Surg Sports Traumatol Arthrosc

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Purpose The aim of this systematic review was to determine if adipose tissue-derived cell-based injectable therapies can induce disease-modifying effects in joints affected by osteoarthritis (OA). Methods A systematic review was performed on three electronic databases (PubMed, Web of Science, Embase) according to PRISMA guidelines. A synthesis of the results was performed investigating disease-modifying effects in preclinical studies comparing injectable adipose-derived products with OA controls or other products, different formulations or injection intervals, and the combination with other products. The risk of bias was assessed according to the SYRCLE’s tool. Results Seventy-one studies were included (2,086 animals) with an increasing publication trend over time. Expanded cells were used in 65 studies, 3 studies applied point of care products, and 3 studies investigated both approaches. Overall, 48 out of 51 studies (94%) reported better results with adipose-derived products compared to OA controls, with positive findings in 17 out of 20 studies (85%) in macroscopic, in 37 out of 40 studies (93%) in histological, and in 22 out of 23 studies (96%) in immunohistochemical evaluations. Clinical and biomarker evaluations showed positive results in 14 studies out of 18 (78%) and 12 studies out of 14 (86%), while only 9 studies out of 17 (53%) of the imaging evaluations were able to detect differences versus controls. The risk of bias was low in 38% of items, unclear in 51%, and high in (11%). Conclusion The current preclinical models document consistent evidence of disease-modifying effects of adipose-derived cell-based therapies for the treatment of OA. The high heterogeneity of the published studies highlights the need for further targeted research to provide recommendations on the optimal methodologies for a more effective application of these injective therapies for the treatment of OA in clinical practice. Level of evidence II. Graphical Abstract

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Section: Discussionsupporting

confidence: 83%

Cell-based therapies have disease-modifying effects on osteoarthritis in animal models. A systematic review by the ESSKA Orthobiologic Initiative. Part 1: adipose tissue-derived cell-based injectable therapies

Orfei

Boffa

Sourugeon

et al. 2022

Knee Surg Sports Traumatol Arthrosc

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“…In fact, imaging evaluations like MRI and radiographs documented disease-modifying effects after cell therapy only in 4 out of 9 studies, often reporting no differences with OA controls. This confirms the limits of the imaging evaluations in detecting changes at cartilage and subchondral bone levels, as already documented in the clinical practice, where there is poor correlation between clinical outcome and imaging findings [ 77 ]. A similar trend was previously observed for adipose-derived products, with immunohistochemical analyses resulting the method able to underline more disease-modifying effects, followed by histological, macroscopic, with imaging evaluations being less useful [ 9 ].…”

Section: Discussionsupporting

confidence: 84%

Cell-based therapies have disease-modifying effects on osteoarthritis in animal models. A systematic review by the ESSKA Orthobiologic Initiative. Part 2: bone marrow-derived cell-based injectable therapies

Boffa

Orfei²,

Sourugeon

et al. 2023

Knee Surg Sports Traumatol Arthrosc

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Purpose Aim of this systematic review was to determine if bone marrow-derived cell-based injectable therapies induce disease-modifying effects in joints affected by osteoarthritis (OA) in animal models. Methods A systematic review was performed on three electronic databases (PubMed, Web of Science, Embase) according to PRISMA guidelines. A synthesis of the results was performed investigating disease-modifying effects in preclinical animal studies comparing injectable bone marrow-derived products with OA controls or other products, different formulations or injection intervals, and the combination with other products. The risk of bias was assessed according to the SYRCLE’s tool. Results Fifty-three studies were included (1819 animals) with an increasing publication trend over time. Expanded cells were used in 48 studies, point-of-care products in 3 studies, and both approaches were investigated in 2 studies. Among the 47 studies presenting results on the disease-modifying effects, 40 studies (85%) reported better results with bone marrow-derived products compared to OA controls, with positive findings evident in 14 out of 20 studies (70%) in macroscopic assessment, in 30 out of 41 studies (73%) in histological assessment, and in 10 out of 13 studies (77%) in immunohistochemical evaluations. Clinical evaluations showed positive results in 7 studies out of 9 (78%), positive imaging results in 11 studies out of 17 (65%), and positive biomarker results in 5 studies out of 10 (50%). While 36 out of 46 studies (78%) reported positive results at the cartilage level, only 3 out of 10 studies (30%) could detect positive changes at the synovial level. The risk of bias was low in 42% of items, unclear in 50%, and high in 8%. Conclusion This systematic review of preclinical studies demonstrated that intra-articular injections of bone marrow-derived products can induce disease-modifying effects in the treatment of OA, slowing down the progression of cartilage damage with benefits at macroscopic, histological, and immunohistochemical levels. Positive results have been also observed in terms of clinical and imaging findings, as well as in the modulation of inflammatory and cartilage biomarkers, while poor effects have been described on the synovial membrane. These findings are important to understand the potential of bone marrow-derived products and to guide further research to optimise their use in the clinical practice. Level of evidence II.

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“…However, products with different degrees of processing, different cell composition and isolated from different anatomical sources are not comparable from a biological perspective, and their clinical effects can differ. 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.…”

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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Effectiveness of AD-MSCs injections for the treatment of knee osteoarthritis: Analysis of the current literature

Cited by 7 publications

References 16 publications

Cell-based therapies have disease-modifying effects on osteoarthritis in animal models. A systematic review by the ESSKA Orthobiologic Initiative. Part 1: adipose tissue-derived cell-based injectable therapies

Cell-based therapies have disease-modifying effects on osteoarthritis in animal models. A systematic review by the ESSKA Orthobiologic Initiative. Part 1: adipose tissue-derived cell-based injectable therapies

Cell-based therapies have disease-modifying effects on osteoarthritis in animal models. A systematic review by the ESSKA Orthobiologic Initiative. Part 2: bone marrow-derived cell-based injectable therapies

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

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