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

Abstract

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.

Stem cells: a potential treatment option for kidney diseases

“…In another pilot study, the treatment of autologous adipose tissue-derived MSCs (AT-MSCs) significantly reduced urinary protein excretion of CKD 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. But no improvement in glomerular filtration rate has been observed [164]. Similarly, another 18-month study showed no significant improvements in renal function of CKD patients who received MSC infusion [165].…”

Use of mesenchymal stem cells for chronic kidney disease

“…Considering complex processes and expensive infrastructures required to produce qualified MSCs, it is difficult to perform large scale, well-designed clinical trials. Many trials, including this study [4], consistently indicated that MSCs may have potential, as a new therapeutic strategy, in combination with standard pharmacologic therapies. There are many issues which should be resolved for MSCs, to become a widely accepted treatment option for CKD patients.…”

“…In the issue of Kidney Research and Clinical Practice , Villanueva et al [4] assessed the efficacy and safety of an injection, of autologous adipose tissue-derived MSCs (AT-MSCs), for treatment of CKD. They infused AT-MSCs intravenously into 6 patients with CKD, at a dose of 1 × 10 6 /kg.…”

“…Additionally, the quality of MSCs can be different in each individual. For example, a patient with diabetic nephropathy was excluded from the study, because of poor proliferation, and resulting low number of AT-MSCs in culture, in this study [4]. So, for mass-production of standardized “cell therapy agent”, allogenic MSCs can be preferred.…”

Mesenchymal Stem Cell Therapy for Diabetic Kidney Disease: A Review of the Studies Using Syngeneic, Autologous, Allogeneic, and Xenogeneic Cells

“…Not only DM but also other chronic diseases, such as CKD, may impair MSC functionality. Autologous AT-MSCs obtained from CKD individuals (stages 3 and 4), when injected intravenously (1 × 10 6 /kg), exhibited a safety profile and contributed to decreasing proteinuria, yet not modifying eGFR in six patients [ 143 ]. Other progenitor cells, such as endothelial progenitor cells, are affected by uremia regardless of the presence of DM [ 144 ].…”