BM-MSCs differentiated to chondrocytes for treatment of full-thickness cartilage defect of the knee.

BACKGROUND: Full-thickness articular cartilage injury of the knee is a major cause of disability. The aim of this study is to assess the outcome of patients treated with differentiated to chondrocytes bone marrow mesenchymal stem cells (BM-MSCs) cultured on a collagen type I/III (Chondro-Gide®) scaffold. The secondary aim was to confirm the absence of adverse events. METHODS: Fifteen patients (19 knees) with symptomatic full-thickness cartilage defects of the knee were enrolled. Bone marrow was harvested from the iliac crest, BM-MSCs were prepared, and expanded cells were grown in a standard medium or in a standard culture medium containing TGF-ß. BM-MSCs differentiated to chondrocytes were seeded in a porcine collagen type I/III scaffold (Chondro-Gide®) and cultured in TGF-ß containing media. After 4 weeks, the membrane was sutured on the cartilage defect. All patients underwent plain radiographs (antero-posterior, lateral, and axial view of the patella) and MRI of the affected knee. The Oxford knee score, the Lyhsolm scale, and the VAS score were administered to all patients. At final follow-up a MRI for the study of articular cartilage was undertaken. RESULTS: The mean size of the cartilage lesions was 20 × 17 mm (range, 15 × 10 mm-30 × 30 mm). At final follow-up, the median Oxford knee score and Lyhsolm scale scores significantly improved from 29 (range 12-39; SD 7.39) to 45 (range 24-48; SD 5.6) and from 55.5 (range 25-81; SD 17.7) to 94.5 (58-100; SD 10.8), respectively. Pain, according to the VAS score, significantly improved. Sixty percent of patients reported their satisfaction as excellent, 20% as good, 14% as fair, and 1 patient as poor. CONCLUSION: The treatment of full-thickness chondral injuries of the knee with differentiated to chondrocytes BM-MSCs and Chondro-Gide® scaffold showed encouraging outcomes. Further studies involving more patients, and with longer follow-up, are required to evaluate the effectiveness of the treatment and the long-term results.

Comparative study of the neural differentiation capacity of mesenchymal stromal cells from different tissue sources: An approach for their use in neural regeneration therapies.

Mesenchymal stem cells (MSCs) can trans/differentiate to neural precursors and/or mature neurons and promote neuroprotection and neurogenesis. The above could greatly benefit neurodegenerative disorders as well as in the treatment of post-traumatic and hereditary diseases of the central nervous system (CNS). In order to attain an ideal source of adult MSCs for the treatment of CNS diseases, adipose tissue, bone marrow, skin and umbilical cord derived MSCs were isolated and studied to explore differences with regard to neural differentiation capacity. In this study, we demonstrated that MSCs from several tissues can differentiate into neuron-like cells and differentially express progenitors and mature neural markers. Adipose tissue MSCs exhibited significantly higher expression of neural markers and had a faster proliferation rate. Our results suggest that adipose tissue MSCs are the best candidates for the use in neurological diseases.

Mesenchymal stem cell therapy in the treatment of hip osteoarthritis.

This study was performed to investigate the safety and efficacy of the intra-articular infusion of ex vivo expanded autologous bone marrow-derived mesenchymal stem cells (BM-MSC) to a cohort of patients with articular cartilage defects in the hip. The above rationale is sustained by the notion that MSCs express a chondrocyte differential potential and produce extracellular matrix molecules as well as regulatory signals, that may well contribute to cure the function of the damaged hip joint. A cohort of 10 patients with functional and radiological evidences of hip osteoarthritis, either in one or both legs, was included in the study. BM-MSC (the cell product) were prepared and infused into the damaged articulation(s) of each patient (60 × 106 cells in 3 weekly/doses). Before and after completion of the cell infusion scheme, patients were evaluated (hip scores for pain, stiffness, physical function, range of motion), to assess whether the infusion of the respective cell product was beneficial. The intra-articular injection of three consecutive weekly doses of ex vivo expanded autologous BM-MSC to patients with articular cartilage defects in the hip and proved to be a safe and clinically effective treatment in the restoration of hip function and range of motion. In addition, the statistical significance of the above data is in line with the observation that the radiographic scores (Tönnis Classification of Osteoarthritis) of the damaged leg(s) remained without variation in 9 out of 10 patients, after the administration of the cell product.

Cell Therapy and Tissue Engineering Approaches for Cartilage Repair and/or Regeneration.

Articular cartilage injuries caused by traumatic, mechanical and/or by progressive degeneration result in pain, swelling, subsequent loss of joint function and finally osteoarthritis. Due to the peculiar structure of the tissue (no blood supply), chondrocytes, the unique cellular phenotype in cartilage, receive their nutrition through diffusion from the synovial fluid and this limits their intrinsic capacity for healing. The first cellular avenue explored for cartilage repair involved the in situ transplantation of isolated chondrocytes. Latterly, an improved alternative for the above reparative strategy involved the infusion of mesenchymal stem cells (MSC), which in addition to a self-renewal capacity exhibit a differentiation potential to chondrocytes, as well as a capability to produce a vast array of growth factors, cytokines and extracellular matrix compounds involved in cartilage development. In addition to the above and foremost reparative options up till now in use, other therapeutic options have been developed, comprising the design of biomaterial substrates (scaffolds) capable of sustaining MSC attachment, proliferation and differentiation. The implantation of these engineered platforms, closely to the site of cartilage damage, may well facilitate the initiation of an 'in situ' cartilage reparation process. In this mini-review, we examined the timely and conceptual development of several cell-based methods, designed to repair/regenerate a damaged cartilage. In addition to the above described cartilage reparative options, other therapeutic alternatives still in progress are portrayed.