Specific effector cell (EC) immunomodulation improves the repair function of adipose mesenchymal stroma cells (aMSC) on an experimental model of grade3-4 osteoarthrosis (OA). Comparation with other current therapies

Abstract

Background & Aim Different cellular therapies for OA knee cartilage repair are limited to grade 1 and 2 lesions. These methods producefibrous cartilage (instead of hyaline) because itsextra cellular matrix (ECM) is impoverished in collagen 2 and enrichedin collagen 1. The small thickness and poor subchondral bone integration make this repaired tissue fragile. To overcome these ECM defects a new therapeutic approach associating the use of tissue specific EC, cocultured withsyngeneicaMSCis presented here. Theapproachwas tested on an animal model of G3-4 OA. Its efficacy was compared with other current therapies Methods, Results & Conclusion Methods 44Wistar rats (250 g)were intra articular (IA) injected with a0.2% solution of mono iodine acetate (MIA, MERK Lab). After 7 days, 4 animals were euthanized and injected joins, as well its contralateral, were collected for 0-day histology controls. The rest of animals were divided into 5 groups of 8 animals each. Group 1 was kept w/o treatment as a Control Group,Group 2 IA treated with syngeneic aMSC, Group 3 with syngeneic activated EC, Group 4 with a co-culture of EC+aMSC and Group 5 with syngeneic PRP. 4 animals of each group were euthanized at day 7, and the remain 4 rats were euthanized for day 14. aMSC were obtained from subdermal, collagenase dissociated, fat tissue. EC, obtained from mechanical dissociatedsplenic cells and 96 hours challenge of hyaline cartilage lysate in RPMI Media culture.EC+aMSCafter 18 hoursco-culture. PRP from blood of complete cardiac bleeding. Histologic exam was done through H&E and Alcian Blue Stains, and IHC stains for Collagens Type 1, 2, and 10, aggrecans, and CD 45+ cells. Results Histologic preparation of control group rats shows, since day 0 through day 14, the effectiveness of MIA IA treatmentproducing Grade 3-4. Almost complete cartilage disappearance, fibrotic scar formation in between both join surfaces, and strong inflammatory reaction at subchondral bone and synovia tissues.All the tested treatments controlled the inflammatory reaction. aMSC treated rats developed fibrous cartilage,and fibrotic scar. EC induces poor hyaline cartilage formation. EC+aMSC co-culture induces almost complete recovery of cartilage,subchondral bone and synovium tissue. PRP, after a transient cartilage protection, induces sever scar formation in between both join surfaces. Conclusion IA injection of EC+aMSC co-culture seems to be effective to repair Grade 3-4 OA hyaline cartilage on this animal model.