Intra-articular delivery of adipose derived stromal cells attenuates osteoarthritis progression in an experimental rabbit model

Abstract

IntroductionCell therapy is a rapidly growing area of research for the treatment of osteoarthritis (OA). This work is aimed to investigate the efficacy of intra-articular adipose-derived stromal cell (ASC) injection in the healing process on cartilage, synovial membrane and menisci in an experimental rabbit model.MethodsThe induction of OA was performed surgically through bilateral anterior cruciate ligament transection (ACLT) to achieve eight weeks from ACLT a mild grade of OA. A total of 2 × 106 and 6 × 106 autologous ASCs isolated from inguinal fat, expanded in vitro and suspended in 4% rabbit serum albumin (RSA) were delivered in the hind limbs; 4% RSA was used as the control. Local bio-distribution of the cells was verified by injecting chloro-methyl-benzamido-1,1'-dioctadecyl-3,3,3'3'-tetra-methyl-indo-carbocyanine per-chlorate (CM-Dil) labeled ASCs in the hind limbs. Cartilage and synovial histological sections were scored by Laverty's scoring system to assess the severity of the pathology. Protein expression of some extracellular matrix molecules (collagen I and II), catabolic (metalloproteinase-1 and -3) and inflammatory (tumor necrosis factor- α) markers were detected by immunohistochemistry. Assessments were carried out at 16 and 24 weeks.ResultsLabeled-ASCs were detected unexpectedly in the synovial membrane and medial meniscus but not in cartilage tissue at 3 and 20 days from ASC-treatment. Intra-articular ASC administration decreases OA progression and exerts a healing contribution in the treated animals in comparison to OA and 4% RSA groups.ConclusionsOur data reveal a healing capacity of ASCs in promoting cartilage and menisci repair and attenuating inflammatory events in synovial membrane inhibiting OA progression. On the basis of the local bio-distribution findings, the benefits obtained by ASC treatment could be due to a trophic mechanism of action by the release of growth factors and cytokines.

Comparison between two different experimental models of osteoarthritis in rabbits. Intra-articular collagenase injection and anterior cruciate ligament transection

“…However, these changes were superficial and showed early osteoarthritis stages due to the collagenase concentration, according to Kikuchi et al 6 . The ACLT method has created degenerative cartilage lesions after 12 weeks, as well as more severe degradation 4,15,16 .…”

Biological Augmentation and Tissue Engineering Approaches in Meniscus Surgery

“…They showed increased vascularization, thinner repair tissue, and better bonding with surrounding tissue when the construct with MSCs was compared with constructs without cells. Desando et al 31 investigated the potential of adipose tissueederived stem cells for meniscus repair, showing that these cells were able to improve healing of cartilage and meniscus defects in a rabbit osteoarthritis model. Finally, although all the studies mentioned point to the potential benefits of stem cell augmentation, in a meniscus pullout suture enhanced with human BMSCs versus simple sutures alone in a rabbit model, Hong et al 32 did not show significantly increased healing in the group treated with suture and cells versus cells alone.…”

Treatment of osteoarthritis with mesenchymal stem cells

“…Giovanna et al [97] noted in the cell-treated group. These successful preclinical studies led to the initiation of many clinical trials (Table 3).…”