Human Osteochondral Explants as an Ex Vivo Model of Osteoarthritis for the Assessment of a Novel Class of Orthobiologics

Pharmaceutics

Paolo Savadori¹  Anna Teresa Brini¹  Chiara Giannasi¹  Sara Casati¹  Giuseppe M. Peretti²  Laura Mangiavini²  Elena Della Morte²  Stefania Niada²  Andrea Ambrosanio³  Andrea Colombo³  Valeria Vismara³ 

[1] Department of Biomedical Surgical and Dental Sciences, University of Milan, 20129 Milan, Italy;IRCCS Istituto Ortopedico Galeazzi, 20161 Milan, Italy;Residency Program in Orthopedics and Traumatology, University of Milan, 20129 Milan, Italy;

关键词: secretome;    conditioned medium;    extracellular vesicle;    mesenchymal cell;    osteoarthritis;    osteochondral explant;   

DOI  :  10.3390/pharmaceutics14061231

来源: DOAJ

【 摘 要 】

Osteoarthritis (OA) is a highly prevalent joint disease still lacking effective treatments. Its multifactorial etiology hampers the development of relevant preclinical models to evaluate innovative therapeutic solutions. In the last decade, the potential of Mesenchymal Stem Cell (MSC) secretome, or conditioned medium (CM), has emerged as an alternative to cell therapy. Here, we investigated the effects of the CM from adipose MSCs (ASCs), accounting for both soluble factors and extracellular vesicles, on human osteochondral explants. Biopsies, isolated from total knee replacement surgery, were cultured without additional treatment or with the CM from 10⁶ ASCs, both in the absence and in the presence of 10 ng/mL TNFα. Tissue viability and several OA-related hallmarks were monitored at 1, 3 and 6 days. Specimen viability was maintained over culture. After 3 days, TNFα induced the enhancement of matrix metalloproteinase activity and glycosaminoglycan release, both efficiently counteracted by CM. The screening of inflammatory lipids, proteases and cytokines outlined interesting modulations, driving the attention to new players in the OA process. Here, we confirmed the promising beneficial action of ASC secretome in the OA context and profiled several bioactive factors involved in its progression, in the perspective of accelerating an answer to its unmet clinical needs.

【 授权许可】

Unknown