Mesenchymal stem cell therapy for knee osteoarthritis: 5 years follow-up of three patients.

AIM: Osteoarthritis is a degenerative joint disease characterized by the destruction of joint cartilage. Mesenchymal stem cells (MSCs) are found in low numbers in normal cartilage, mainly in the superficial layer, acting as repairing agents. In OA, MSCs are seen in larger numbers, but act chaotic and are unable to repair the cartilage. The synovial membrane becomes inflamed and interacts with the cartilage. Transplanted MSC have the ability to normalize them, redirecting them to their normal function. In a preliminary study, we showed that MSC could improve knee OA in four patients at 6 months. This report shows their long-term follow-up at 5 years. METHODS: One patient was lost to follow-up at 2 years and three were followed for 5 years. They were aged 55, 57, 65 and 54 years, and had moderate to severe knee osteoarthritis. The worse knee of each patient was injected with 8-9 × 10(6) MSC. RESULTS: As previously reported, all parameters improved in transplant knees at 6 months (walking time, stair climbing, gelling pain, patella crepitus, flection contracture and the visual analogue score on pain). Then, they started gradually to deteriorate, but at 5 years they were still better than at baseline. PGA (Patient Global Assessment) improved from baseline to 5 years. The better knee at baseline (no MSC), continued its progression toward aggravation and at 5 years became the worse knee. CONCLUSION: Transplant knees were all in a rather advanced stage of OA. Earlier transplantation may give better results in long-term follow-up. This is what future studies have to demonstrate.

Mesenchymal stem cell therapy unable to rescue the vision from advanced Behcet's disease retinal vasculitis: report of three patients.

OBJECTIVE: Retinal vasculitis (RV) is the most aggressive lesion of ocular manifestations of Behcet's disease, seen in 32.1% of patients. Although visual acuity (VA) improves with early and aggressive treatment, in the long run it is seen in only 48% of patients. Mesenchymal stem cell (MSC) transplantation (MSCT) can theoretically reverse the RV process. PATIENTS AND METHODS: Three patients with advanced RV and very low VA were selected. Eyes selected for MSCT were legally blind (no useful vision) with severe retinal damage due to vasculitis, resistant to combinations of monthly pulse-cyclophosphamide (1000 mg) + azathioprine 2-3 mg/kg/day + prednisolone 0.5 mg/kg/day. After patient signed written consent, 30 mL of bone marrow were taken and cultured for MSC growth. After having enough MSCs in culture (4-5 weeks) and taking into consideration all safety measures, cells were injected in one eye of each patient (approximately 1.8 million MSCs). VA was measured. Disease Activity Index (DAI) was calculated for anterior uveitis (AU), posterior uveitis (PU) and RV. RESULTS: Visual acuity was light perception (LP) for two patients and finger count (FC) for the third. Follow-up at 1, 6 and 12 months were respectively LP/LP/FC at 0.5 m, no-light perception (NLP)/LP/LP, NLP/LP/NLP. DISCUSSION: Results showed a total failure of the procedure, essentially due to the late and advanced state of vasculitis. However, the autoimmune/inflammatory reaction was greatly controlled by the procedure. CONCLUSION: Earlier cases have to be selected for further trials.

Mesenchymal stem cell therapy for knee osteoarthritis. Preliminary report of four patients.

BACKGROUND: Osteoarthritis (OA) is a cartilage degenerative process, involving the immune system, producing local inflammatory reactions, with production of pro-inflammatory cytokines and metalloproteinases. No treatment is still available to improve or reverse the process. Stem cell therapy opened new horizons for treatment of many incurable diseases. Mesenchymal stem cells (MSCs) due to their multi-lineage potential, immunosuppressive activities, limited immunogenicity and relative ease of growth in culture, have attracted attentions for clinical use. AIM: The aim of this study was to examine whether MSC transplantation could reverse the OA process in the knee joint. The project was approved by the Tehran University of Medical Sciences Research Committee and Ethical Committee. PATIENTS AND METHODS: Four patients with knee osteoarthritis were selected for the study. They were aged 55, 57, 65 and 54 years, and had moderate to severe knee OA. After their signed written consent, 30 mL of bone marrow were taken and cultured for MSC growth. After having enough MSCs in culture (4-5 weeks) and taking in consideration all safety measures, cells were injected in one knee of each patient. RESULTS: The walking time for the pain to appear improved for three patients and remained unchanged for one. The number of stairs they could climb and the pain on visual analog scale improved for all of them. On physical examination, the improvement was mainly for crepitus. It was minor for the improvement of the range of motion. CONCLUSION: Results were encouraging, but not excellent. Improvement of the technique may improve the results.

Chimerism: a new look.

INTRODUCTION: Microchimerism has become a familiar term in the past few years. Many groups all over the globe, specializing in a diverse array of basic and medical sciences, have turned their attention to microchimerism, its possible role in disease or repair, and its mechanism of action in the host body. We reviewed the current knowledge about this novel term. MATERIALS AND METHODS: We search the PubMed, using all the derivatives of chimera. All papers and their bibliographic information published by December 2005 were reviewed and 61 were selected. RESULTS: Microchimerism is the presence of foreign or nonhost cells in a body. These are cells that live, differentiate, and persist in the host body by definition. These cells can enter the host body in a variety of manners. The most familiar aspect is microchimerism resulting from organ transplant. For many years now scientists have been debating over the interpretation of this phenomenon. We know that donor cell engraftment in the recipient body is a sign of transplantation success. What this means is that the body has developed tolerance toward the foreign organ and created a chimer. CONCLUSION: How long this chimeric state will last, whether these cells will induce or be induced to create a chronic complication in the long run, or will these genetically distinct cell types live peacefully in one body to the end of the host's life are the essence of the ongoing discussion and what probes researchers to continue their search.