Repair of Torn Avascular Meniscal Cartilage Using Undifferentiated Autologous Mesenchymal Stem Cells: From In Vitro Optimization to a First-in-Human Study. Stem Cells

Meniscal cartilage tears are common and predispose to osteoarthritis (OA). Most occur in the avascular portion of the meniscus where current repair techniques usually fail. We described previously the use of undifferentiated autologous mesenchymal stem cells (MSCs) seeded onto a collagen scaffold (MSC/collagen-scaffold) to integrate meniscal tissues in vitro. Our objective was to translate this method into a cell therapy for patients with torn meniscus, with the long-term goal of delaying or preventing the onset of OA. After in vitro optimization, we tested an ovine-MSC/collagen-scaffold in a sheep meniscal cartilage tear model with promising results after 13 weeks, although repair was not sustained over 6 months. We then conducted a single center, prospective, open-label first-in-human safety study of patients with an avascular meniscal tear. Autologous MSCs were isolated from an iliac crest bone marrow biopsy, expanded and seeded into the collagen scaffold. The resulting human-MSC/collagen-scaffold implant was placed into the meniscal tear prior to repair with vertical mattress sutures and the patients were followed for 2 years. Five patients were treated and there was significant clinical improvement on repeated measures analysis. Three were asymptomatic at 24 months with no magnetic resonance imaging evidence of recurrent tear and clinical improvement in knee function scores. Two required subsequent meniscectomy due to retear or nonhealing of the meniscal tear at approximately 15 months after implantation. No other adverse events occurred. We conclude that undifferentiated MSCs could provide a safe way to augment avascular meniscal repair in some patients. Registration: EU Clinical Trials Register, 2010-024162-22. STEM CELLS TRANSLATIONAL MEDICINE 2017;6:1237–1248 SIGNIFICANCE STATEMENT Each knee has two menisci (medial and lateral) that sit in between the articular cartilage surfaces found at the ends of the upper-leg and lower-leg bones. Tears to the meniscus are a common injury caused by excessive twisting force to the knee. Current standard of care for avascular meniscal tears requires surgical removal of the damaged tissue (meniscectomy). However, meniscectomy compromises knee function and leads to associated clinical consequences such as knee replacement surgery and a negative impact on quality of life. The authors have developed a therapy combining undifferentiated mesenchymal stem cells with a collagen scaffold to drive healing of the meniscal tear, so avoiding meniscectomy. The preliminary clinical data are encouraging and suggest for the first time that repair of avascular meniscal tears is possible.