Physioxia Expanded Bone Marrow Derived Mesenchymal Stem Cells Have Improved Cartilage Repair in an Early Osteoarthritic Focal Defect Model

Abstract

Focal early osteoarthritis (OA) or degenerative lesions account for 60% of treated cartilage defects each year. The current cell-based regenerative treatments have an increased failure rate for treating degenerative lesions compared to traumatic defects. Mesenchymal stem cells (MSCs) are an alternative cell source for treating early OA defects, due to their greater chondrogenic potential, compared to early OA chondrocytes. Low oxygen tension or physioxia has been shown to enhance MSC chondrogenic matrix content and could improve functional outcomes of regenerative therapies. The present investigation sought to develop a focal early OA animal model to evaluate cartilage regeneration and hypothesized that physioxic MSCs improve in vivo cartilage repair in both, post-trauma and focal early OA defects. Using a rabbit model, a focal defect was created, that developed signs of focal early OA after six weeks. MSCs cultured under physioxia had significantly enhanced in vitro MSC chondrogenic GAG content under hyperoxia with or without the presence of interleukin-1β (IL-1β). In both post-traumatic and focal early OA defect models, physioxic MSC treatment demonstrated a significant improvement in cartilage repair score, compared to hyperoxic MSCs and respective control defects. Future investigations will seek to understand whether these results are replicated in large animal models and the underlying mechanisms involved in in vivo cartilage regeneration.

Research Progress on Stem Cell Therapies for Articular Cartilage Regeneration

“…Additionally, hypoxic pretreatment can also upregulate genes related to growth, cell signaling, metabolism, and cellular stress response pathways [ 113 ]. In a rabbit knee joint trauma and focal early OA model, hypoxia-pretreated MSC+HA hydrogel caused a significant improvement in the cartilage repair score [ 114 ]. The mechanism through which hypoxia affects cells is mainly regulated by HIF-1.…”

The Role of Extracellular Vesicles in the Pathogenesis, Diagnosis, and Treatment of Osteoarthritis

“…However, research by Hu et al showed that when cells were cultured at an oxygen concentration lower than 0.5%, hypoxic pretreatment (HP) increased MSC migration and reduced MSC apoptosis [ 71 ]. In terms of OA and cartilage repair, in rabbit knee joint trauma and focal early OA models, aerobic MSC treatment significantly improved cartilage repair scores compared with hyperoxic MSC and their respective control defects [ 72 ]. Rong et al found that EVs derived from BMSCs treated with hypoxia-inducible factor 1α-induced hypoxic can promote chondrocyte proliferation, migration, and inhibit apoptosis through the miR-216a-5p/JAK2/STAT3 signaling pathway as well as mediate cartilage repair in osteoarthritis [ 73 ].…”

Nanoparticle-Based Drug Delivery System—A Target Strategy for Osteoarthritis Treatment

“…The joint focal defect method is an ideal model for observing the early manifestations and treatment effects of OA. It is particularly sensitive in observing the therapeutic effects of cartilage protection and repair [112,113].…”