Intra-articular injection of autologous adipose-derived mesenchymal stem cells in the treatment of knee osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a chronic degenerative joint disease and is considered to be the fourth leading cause of disability and the second cause of inability to work in men. Recently, adipose-derived mesenchymal stem cells (AD-MSCs) came into focus for regenerative medicine as a promising tool for the treatment of OA. The administration of stem cells into impaired joints results in pain relief and improves quality of life, accompanied by restoration of hyaline articular cartilage. METHODS: In the present study, nine patients (including two patients with bilateral symptoms) diagnosed with osteoarthritis (International Knee Documentation grade B in 5 and grade D in six knees) were treated using a single injection of AD-MSCs at a concentration of 0.5-1.0 × 107 cells and were followed up for 18 months. During follow-up, all the cases were evaluated clinically by Knee Society score (KSS), Hospital for Special Surgery knee score (HSS-KS), Tegner-Lysholm (T-L) score and visual analogue scale (VAS) of pain, as well as by plain radiography and by magnetic resonance imaging visualization with 2D Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score assessment. RESULTS: Significant improvement of all four clinical scores was observed within the first 6 months (KSS for 41.4 points, HSS-KS for 33.9 points, T-L score for 44.8 points, VAS of pain from 54.5 to 9.3) and improvement persisted throughout the rest of the follow-up. MOCART score showed significant cartilage restoration (from 43 ± 7.2 to 63 ± 17.1), whereas radiography showed neither improvement, nor further joint degeneration. CONCLUSIONS: The results obtained in the present study provide good basis for prospective randomized controlled clinical trials with respect to the use of AD-MSCs in the treatment of osteoarthritis.

Association between active pulmonary tuberculosis and miRNA-146a: A preliminary study from Serbia.

INTRODUCTION: Tuberculosis (TB) continues to be a significant public health problem. The role of small non-coding RNAs, such as microRNAs (miRNAs), was investigated extensively in Mycobacterium tuberculosis (MTB) infection as well as in a variety of other pathophysiological processes in recent years. It was found that miRNAs act as regulators of both early reaction to MTB infection and in process of adaptation of the host immune cells during latent course of the disease. Molecule miRNA-146a is expressed exclusively in immune cells and it has the most prominent role in modulation of innate immunity. METHODOLOGY: We investigated the level of expression of miRNA-146a using an RT-qPCR technique in peripheral blood mononuclear cells of 44 patients with active pulmonary TB and 17 healthy individuals. We also analyzed the significance of miRNA-146a rs2910164 SNV for expression profile of miRNA-146a, in order to investigate potential usage of miRNA-146a as a biomarker for TB. RESULTS: There was statistically significant decrease of expression of miRNA-146a in TB group compared to control group. When gender cohorts were analyzed, the expression levels in TB male and TB female subgroup were significantly lower than the expression levels in the same gender control subgroups. CONCLUSIONS: Our results indicate that miRNA-146a plays a significant role in the pathogenesis of TB, suggesting that miRNA-146a could be used as a biomarker for active pulmonary TB.

Relevance of TNF-α, IL-6 and IRAK1 gene expression for assessing disease severity and therapy effects in tuberculosis patients.

INTRODUCTION: Tuberculosis (TBC) is a contagious chronic respiratory disease which despite the known cause, Mycobacterium tuberculosis (Mtb), and many decades of successful therapy, remains one of the leading global health problems. Immune responses against Mtb infection involve both of types of immunity, but cellular immunity, in which certain cytokines and Th1 cells play a key role, is crucial. A better understanding of the functions of the cytokine network involved in the state and progression of TBC could identify specific molecular markers for monitoring of disease activity as well as therapy outcomes in TBC patients. METHODOLOGY: We investigated expression of TNF-α, IL-6 and IRAK1 genes using an RT-qPCR technique in peripheral blood mononuclear cells of 33 TBC patients and 10 healthy individuals. RESULTS: Comparison between TBC patients and healthy individuals revealed statistically significant differences for all analyzed genes. The levels of expression of TNF-α and IL-6 mRNA were higher, while the level of IRAK1 mRNA was lower in the TBC group compared to controls. Moreover, a strong positive correlation was observed between TNF-α and IL-6 gene expression. When clinical parameters were analyzed, increased levels of TNF-α mRNA were detected in patients with a longer duration of therapy (>2 months) compared to those with a shorter therapy duration (< 2 months), and in patients without anemia. CONCLUSIONS: Our results indicate that the inflammatory genes we examined play a crucial role in the pathogenesis of tuberculosis, and that the expression of the TNF-α gene could be a marker for monitoring the clinical effect of the ant-tuberculosis drugs during therapy.