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

Abstract

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

Clinical Efficacy and Safety of the Intra-articular Injection of Autologous Adipose-Derived Mesenchymal Stem Cells for Knee Osteoarthritis: A Phase III, Randomized, Double-Blind, Placebo-Controlled Trial

“…31 Meanwhile, preclinical models have documented evidence of the disease-modifying effects of ADMSCs for the treatment of knee osteoarthritis in macroscopic, histologic, and immunohistochemical evaluations. 42 According to preclinical studies, the promising effects of ADMSCs could skew the biochemical environment of osteoarthritis into regenerative and anti-inflammatory conditions via paracrine effects. 11,23,40,42 A recent midterm clinical study showed significant improvement in cartilage changes between 2 and 3 years after a single IA injection of ADMSCs based on serial MRI evaluation.…”

“…42 According to preclinical studies, the promising effects of ADMSCs could skew the biochemical environment of osteoarthritis into regenerative and anti-inflammatory conditions via paracrine effects. 11,23,40,42 A recent midterm clinical study showed significant improvement in cartilage changes between 2 and 3 years after a single IA injection of ADMSCs based on serial MRI evaluation. 32 Thus, structural cartilage improvement requires a longer follow-up to reflect the regenerative and chondroprotective effects of ADMSCs.…”

“…1,31,51 In experimental models, ADMSC-based therapies have shown consistent evidence of disease-modifying effects for the treatment of osteoarthritis based on a recent systematic review of preclinical studies. 42 However, clinical evidence of ADMSCbased therapies remains limited. 18,22 In 2019, a phase IIb clinical randomized controlled trial (RCT) of an intra-articular (IA) injection of autologous high-dose ADMSCs (1 3 10 8 cells) demonstrated the safety and effectiveness of this treatment for knee osteoarthritis at 6-month follow-up in an outpatient setting, with results of pain relief and functional improvement without structural aggravation.…”

“…1,31,51 In experimental models, ADMSC-based therapies have shown consistent evidence of disease-modifying effects for the treatment of osteoarthritis based on a recent systematic review of preclinical studies. 42 However, clinical evidence of ADMSC-based therapies remains limited. 18,22…”

Midterm results of intra‐articular stromal vascular fraction injection for the treatment of knee osteoarthritis

“…Cavallo et al reported that bone marrow aspirate concentrate (BMAC) obtained from the iliac crest and proximal tibia presents the potential for osteogenic and chondrogenic differentiation as well as mesenchymal marker expression [9]. Perucca Orfei C et al reported in a systematic review that injectable adipose‐derived cell‐based therapies showed positive effects on joint tissues in animal osteoarthritis models, provided a structural/macroscopic improvement in both the cartilage and synovial membrane properties compared to untreated osteoarthritis joints and reduced the serum and synovial fluid levels of cartilage destruction markers [22].…”