TY - JOUR
T1 - 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
AU - Pers, Yves Marie
AU - Quentin, Julie
AU - Feirreira, Rosanna
AU - Espinoza, Francisco
AU - Abdellaoui, Naoill
AU - Erkilic, Nejla
AU - Cren, Maïlys
AU - Dufourcq-Lopez, Emilie
AU - Pullig, Oliver
AU - Nöth, Ulrich
AU - Jorgensen, Christian
AU - Louis-Plence, Pascale
N1 - Funding Information:
This work was supported by research funding from the European Union 7th FWP under grant agreement 241719 (ADIPOA), from the ANR infrastructure project (N° 11-INBS-0005 “ECELLFRA NCE: Development of a national adult mesenchymal stem cell-based therapy platform”) and from institutional fundings.
Publisher Copyright:
© Ivyspring International Publisher.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
KW - Adipose-derived stromal cells
KW - Immune monitoring
KW - Immunomodulation
KW - Mesenchymal stromal cells
KW - Multiparametric flow cytometry
KW - Osteoarthritis
KW - Adipose-derived stromal cells
KW - Immune monitoring
KW - Immunomodulation
KW - Mesenchymal stromal cells
KW - Multiparametric flow cytometry
KW - Osteoarthritis
UR - http://www.scopus.com/inward/record.url?scp=85057157698&partnerID=8YFLogxK
U2 - 10.7150/thno.27674
DO - 10.7150/thno.27674
M3 - Article
C2 - 30555561
AN - SCOPUS:85057157698
SN - 1838-7640
VL - 8
SP - 5519
EP - 5528
JO - Theranostics
JF - Theranostics
IS - 20
ER -