Intra-articular Delivery of Purified Mesenchymal Stem Cells from C57BL/6 or MRL/MpJ Superhealer Mice Prevents Posttraumatic Arthritis

Abstract

Joint injury dramatically enhances the onset of osteoarthritis (OA) and is responsible for an estimated 12% of OA. Post-traumatic arthritis (PTA) is especially common after intraarticular fracture, and no disease-modifying therapies are currently available. We hypothesized that the delivery of mesenchymal stem cells (MSCs) would prevent PTA by altering the balance of inflammation and regeneration after fracture of the mouse knee. Additionally, we examined the hypothesis that MSCs from the MRL/MpJ (MRL) “superhealer” mouse strain would show increased multilineage and therapeutic potentials as compared to those from C57BL/6 (B6) mice, as MRL mice have shown exceptional in vivo regenerative abilities. A highly purified population of MSCs was prospectively isolated from bone marrow using cell surface markers (CD45−/TER119−/PDGFRα+/Sca-1+). B6 MSCs expanded greater than 100,000 fold in three weeks when cultured at 2% oxygen and displayed greater adipogenic, osteogenic, and chondrogenic differentiation as compared to MRL MSCs. Mice receiving only a control saline injection after fracture demonstrated PTA after 8 weeks, but the delivery of 10,000 B6 or MRL MSCs to the joint prevented the development of PTA. Cytokine levels in serum and synovial fluid were affected by treatment with stem cells, including elevated systemic interleukin-10 at several time points. The delivery of MSCs did not reduce the degree of synovial inflammation but did show increased bone volume during repair. This study provides evidence that intra-articular stem cell therapy can prevent the development of PTA after fracture and has implications for possible clinical interventions after joint injury before evidence of significant OA.

MiR-140 in cancer and beyond: a brief update

“…Interestingly, artificial hypoxia-like states, such as exercise, can induce autophagy [63] . The hypoxic state has a significant effects on understanding [64] , prevention and stem cell/progenitor cell-related therapy for both cancer and OA [65,66]. Elucidating the interplay between autophagy, cancer and OA will provide unique opportunities to identify new therapeutic targets [67] and to develop novel treatment strategies and reduction of the side-effects of those affected by cancer chemotherapy via targeting both cellular homeostasis mechanisms, such as autophagy, and miRNAs epigenetics.…”

Not All Stem Cells Are Equally Great: Donor Single-Nucleotide Polymorphisms (SNP) May Matter More Than Previously Thought

“…36 In fact, MSC transplantation has been emerging as one of the most promising methods for treating OA and has been demonstrated in several animal models. [37][38][39] In addition, registered in website Clinicaltrials.gov is more than 50 proof-of-concept clinical trials. Many trials revolve around the intra-articular injection of autologous bone marrow-or adipose-derived MSCs.…”

Immune Modulation to Improve Tissue Engineering Outcomes for Cartilage Repair in the Osteoarthritic Joint

“…119 Moreover, intra-articular injection of adipose-derived stem cells (ASCs) has been shown to reduce synovial lining thickness and decrease cartilage damage in a collagenase-induced OA mouse model. 120 ASCs were identified in close proximity to synovial macrophages and reduced IL-1b gene expression levels were detected in synovial tissue, indicating immunomodulatory activity of these stem cells within the OA joint.…”