Injection of Adipose-Derived Stromal Cells in the Knee of Patients with Severe Osteoarthritis has a Systemic Effect and Promotes an Anti-Inflammatory Phenotype of Circulating Immune Cells

Abstract

Rationale: Recent studies confirmed that osteoarthritis (OA) is associated with systemic inflammation. Adipose-derived stromal cells (ASCs) could become the most promising cell-based therapy in OA, based not only on their differentiation capacities and trophic and paracrine effects on the existing cartilage, but also on their immunomodulatory properties. Here, we wanted to determine the biological effect of autologous ASC intra-articular (IA) injection.Method: To this aim, we monitored the profile of immune cells in fresh peripheral blood after IA injection of autologous ASCs in the knee of 18 patients with severe OA (ADIPOA phase I study). Specifically, we used 8-color flow cytometry antibody panels to characterize the frequencies of innate and adaptive immune cell subsets (monocytes, dendritic cells, regulatory T cells and B cells) in blood samples at baseline (before injection) and one week, one month and three months after ASC injection.Results: We found that the percentage of CD4+CD25highCD127lowFOXP3+ regulatory T cells was significantly increased at 1 month after ASC injection, and this effect persisted for at least 3 months. Moreover, CD24highCD38high transitional B cells also were increased, whereas the percentage of classical CD14+ monocytes was decreased, at 3 months after ASC injection. These results suggest a global switch toward regulatory immune cells following IA injection of ASCs, underscoring the safety of ASC-based therapy. We did not find any correlation between the scores for the Visual Analogic Scale for pain, the Western Ontario and McMaster Universities Osteoarthritis Index (pain subscale and total score) at baseline and the immune cell profile changes, but this could be due to the small number of analyzed patients.Conclusion: ASCs may drive an immediate local response by releasing paracrine factors and cytokines, and our results suggest that ASCs could also initiate a cascade resulting in a long-lasting systemic immune modulation.

<p>Development and Prospect of Intra-Articular Injection in the Treatment of Osteoarthritis: A Review</p>

“…He proposed that the regulation of congenital and acquired immunity may be the mechanism of AMSCs. 84 Russo et al also confirmed that AMSCs are not only a safe therapy, but also found a significant improvement in VAS score, International Knee Documentation Committee (IKDC) score and Tegner-Lysholm (TL) score during oneyear follow-up. 85 Hudetz et al studied the results of the injection of adipose-derived mesenchymal stem cells (AMSCs) from clinic and imaging, respectively.…”

Mesenchymal Stromal Cell Immunology for Efficient and Safe Treatment of Osteoarthritis

“…They reported that participants who received low dose of MSCs had the best response in terms of pain and function (Pers et al, 2016). A later study by the same group found that injection of AT-MSCs in the knee triggers a systemic long-lasting immune modulation involving an increase in the percentage of CD4 + CD25 high CD127 low FOXP3 + regulatory T cells and CD24 high CD38 high transitional B cells (Pers et al, 2018b).…”

Exosomes From Adipose-Derived Stem Cells: The Emerging Roles and Applications in Tissue Regeneration of Plastic and Cosmetic Surgery

“…In a clinical trial, Spasovski pointed out that the OA patients treated with single injection of ASCs showed significant cartilage restoration (Spasovski et al, 2018). Similarly, in another trial of OA patients received with ASCs, the ASCs might cause an immediate local response due to released paracrine factors and cytokines for OA amelioration (Pers et al, 2018). Tran et al (2019) employed SVF to regenerate damaged knee cartilage of OA patients, revealing a trend toward a better efficacy of SVF with the microfracture method for OA treatment over a period of two years.…”