Sheng‐Hao Chiu

The unique immunomodulatory properties of mesenchymal stem cells (MSCs) make them an invaluable cell type for the repair of tissue/ organ damage caused by chronic inflammation or autoimmune disorders. Although they hold great promise in the treatment of immune disorders such as graft versus host disease (GvHD) and allergic disorders, there remain many challenges to overcome before their widespread clinical application. An understanding of the biological properties of MSCs will clarify the mechanisms of MSC-based transplantation for immunomodulation. In this review, we summarize the preclinical and clinical studies of MSCs from different adult tissues, discuss the current hurdles to their use and propose the future development of pluripotent stem cell-derived MSCs as an approach to immunomodulation therapy.

OBJECTIVES: To study the link between metabolic syndrome (MetS), endothelial injury, and atherosclerosis in patients with systemic lupus erythematosus (SLE). METHODS: Consecutive SLE patients without a history of arterial thrombosis were screened for atherosclerosis at the carotid and coronary arteries by B-mode ultrasound [intima-media thickness (IMT)] and multidetector computed tomography (MDCT) scan (Agatston calcium scores), respectively. Plasma levels of homocysteine, high-sensitivity C-reactive protein (hsCRP), soluble vascular cell adhesion molecule (sVCAM)-1, P-selectin, and soluble thrombomodulin (sTM) were assayed. Patients were stratified according to the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) criteria for MetS, using the Asian criteria for abdominal obesity. Risk factors for atherosclerosis were studied. RESULTS: Of the 123 SLE patients (93% women; age 47.9+/-11 years; SLE duration 10.9+/-7.0 years) studied, 20 (16.3%) had MetS. The prevalence of MetS in the SLE patients was significantly higher than in 492 age- and sex-matched healthy controls (9.6%; p=0.03). Coronary calcification and abnormal carotid IMT were detected in 38 (31%) and 72 (59%) of SLE patients, respectively. Patients with MetS had a significantly higher Agatston score (69.5+/-95 vs. 16.4+/-57; p=0.03) and a numerically higher carotid IMT (p=0.43) than those without. In a logistic regression model, the MetS [odds ratio (OR) 3.11, 95% confidence interval (CI) 1.01-9.59, p=0.049] was associated with coronary atherosclerosis after adjustment for age and other risk factors. In addition, patients with MetS had significantly higher levels of hsCRP (p=0.002), homocysteine (p=0.03), and sTM (p=0.01). CONCLUSIONS: The MetS is more prevalent in SLE patients than the general population and is associated with endothelial injury and coronary atherosclerosis. More aggressive control of risk factors is justified in these patients.

ABSTRACT Liver fibrosis is a progressive disease that can lead to cirrhosis and liver failure, with limited treatment options. Wharton's jelly‐derived MSCs (WJ‐MSCs) have immunomodulatory and antifibrotic potential. Hypoxia preconditioning enhances MSC survival and paracrine activity, but its effects in liver fibrosis remain unclear. This study compares hypoxia and normoxia WJ‐MSCs in a CCl 4 ‐induced liver fibrosis rat model. Sprague–Dawley rats received chronic CCl 4 to induce fibrosis. At Week 8, normoxia or hypoxia WJ‐MSCs were injected via the portal vein. Liver function was assessed using biochemical markers (ALT, AST, T‐Bil, albumin), PET/MR imaging, and qPCR for IL‐1β and IL‐6. Fibrosis regression was evaluated via ultrasound, histology, and collagen quantification. Regeneration was analyzed through Ki67 immunostaining and qPCR for Ki67 and HGF. MSC engraftment was determined by hNA immunohistochemistry. Both normoxia and hypoxia WJ‐MSCs improved liver function, with hypoxia WJ‐MSCs showing greater AST and T‐Bil reductions. PET/MR imaging demonstrated superior metabolic recovery in the hypoxia group, with greater 18 F‐FDG uptake reduction. Histological analysis confirmed more significant fibrosis regression and collagen reduction in the hypoxia group. Gene expression analysis showed stronger suppression of TGF‐β, α‐SMA, and collagen I. Liver regeneration markers Ki67 and HGF were significantly upregulated with a greater HGF increase in the hypoxia group. Additionally, hypoxia WJ‐MSCs exhibited higher engraftment and reduced pulmonary entrapment, indicating improved liver homing. Both normoxia and hypoxia WJ‐MSCs improved liver fibrosis, but hypoxia preconditioning further enhanced liver function, fibrosis regression, and metabolic recovery, supporting its therapeutic superiority.