Adipose tissue-derived mesenchymal stromal cells for treating chronic kidney disease: A pilot study assessing safety and clinical feasibility

BACKGROUND: Chronic kidney disease (CKD) is a growing public health concern, and available treatments are insufficient in limiting disease progression. New strategies, including regenerative cell-based therapies, have emerged as therapeutic alternatives. Results from several groups, including our own, have reported evidence of a supportive role for mesenchymal stromal cells (MSCs) in functional recovery and prevention of tissue damage in murine models of CKD. Prompted by these data, an open pilot study was conducted to assess the safety and efficacy of a single injection of autologous adipose tissue-derived MSCs (AT-MSCs) for treatment of CKD. METHODS: AT-MSCs were infused intravenously into six CKD patients at a dose of 1 million cells/kg. Patients were stabilized and followed for one year prior to MSC infusion and one year following infusion. RESULTS: No patients presented with adverse effects. Statistically significant improvement in urinary protein excretion was observed in AT-MSCs transplanted patients, from a median of 0.75 g/day (range, 0.15–9.57) at baseline to 0.54 g/day (range, 0.01v2.66) at month 12 (P = 0.046). The glomerular filtration rate was not significantly decreased post-infusion of AT-MSCs. CONCLUSION: Findings from this pilot study demonstrate that intravenous infusion of autologous expanded AT-MSCs into CKD patients was not associated with adverse effects and could benefit patients already undergoing standard medical treatment.

Coculture Effects on the Osteogenic Differentiation of Human Mesenchymal Stromal Cells

Cell-based bone regeneration is generally pursued based on single cell type approaches, for which human adipose tissue-derived mesenchymal stromal cells (AT-MSCs) are frequently used, owing to their easy accessibility and relatively large yield. In view of multiple cell types involved in physiological bone regeneration, this study aimed to evaluate the osteogenic differentiation of AT-MSCs upon co-culture with endothelial cells or macrophages in a direct or indirect in vitro co-culture set-up. Our hypotheses were that 1) endothelial cells and macrophages stimulate AT-MSCs proliferation and osteogenic differentiation and that 2) these two cell types will more profoundly affect osteogenic differentiation of AT-MSCs in a direct compared to an indirect co-culture set-up, because of the possibility for both cell-cell interactions and effects of secreted soluble factors in the former. Osteogenic differentiation of AT-MSCs was stimulated by endothelial cells, particularly in direct co-cultures. Although initial numbers of AT-MSCs in co-culture with endothelial cells were 50% compared to monoculture controls, equal levels of mineralization were achieved. Macrophages showed a variable effect on AT-MSCs behavior for indirect co-cultures and a negative effect on osteogenic differentiation of AT-MSCs in direct co-cultures, the latter likely due to species differences of the cell types used. The results of this study demonstrate potential for cell combination strategies in bone regenerative therapies.

Effect of Rehmannia Glutinosa Oligosaccharide on Apoptosis of Human Adipose Tissue-derived Mesenchymal Stromal Cells Induced by Hydrogen Peroxide / 中国康复理论与实践

@#Objective To investigate the influence of rehmannia glutinosa oligosaccharide(RGOs)on apoptosis of human adipose tissue-derived mesenchymal stromal cells(ADMSCs)induced by hydrogen peroxide(H2O2).Methods Cultured human ADMSCs were randomly divided into three groups as the normal group(group N,without any treatment),H2O2 group(group H,treated with 0.1 mmol/L H2O2),and RGOs group(group R,treated with 0.2g/L RGOs plus 0.1 mmol/L H2O2).After 1 h,6 h and 24 h,morphological changes of ADMSCs apoptotic were observed,the apoptotic rate was determined by flow cytometry.Results After 1 h,6 h and 24 h,the apoptotic rate of group H was significantly higher than that of the group N and group R(P<0.05),and the apoptotic rate of group H was significantly higher than that of the group R(P<0.05).Conclusion RGOs can attenuate apoptosis of human ADMSCs induced by H2O2.