The Promise of Mesenchymal Stem Cell Therapy for Diabetic Kidney Disease

Abstract

Diabetes mellitus (DM) commonly leads to progressive chronic kidney disease despite current best medical practice. The pathogenesis of diabetic kidney disease (DKD) involves a complex network of primary and secondary mechanisms with both intra-renal and systemic components. Apart from inhibition of the renin angiotensin aldosterone system, targeting individual pathogenic mediators with drug therapy has not, thus far, been proven to have high clinical value. Stem or progenitor cell therapies offer an alternative strategy for modulating complex disease processes through suppressing multiple pathogenic pathways and promoting pro-regenerative mechanisms. Mesenchymal stem cells (MSCs) have shown particular promise based on their accessibility from adult tissues and their diverse mechanisms of action including secretion of paracrine anti-inflammatory and cyto-protective factors. In this review, the progress toward clinical translation of MSC therapy for DKD is critically evaluated. Results from animal models suggest distinct potential for systemic MSC infusion to favourably modulate DKD progression. However, only a few early phase clinical trials have been initiated and efficacy in humans remains to be proven. Key knowledge gaps and research opportunities exist in this field. These include the need to gain greater understanding of in vivo mechanism of action, to identify quantifiable biomarkers of response to therapy and to define the optimal source, dose and timing of MSC administration. Given the rising prevalence of DM and DKD worldwide, continued progress toward harnessing the inherent regenerative functions of MSCs and other progenitor cells for even a subset of those affected has potential for profound societal benefits.

Mesenchymal Stem Cells as Therapeutic Candidates for Halting the Progression of Diabetic Nephropathy

“…As previously reported, cell-based strategy utilizing MSCs therapy is very promising for tissue regeneration [111], including DN [35, 58]. MSCs show preferential migration toward sites of inflammation, injury, and cancer, suggesting that these cells may be attractive hypoimmunogenic cellular vehicles for drug and gene delivery [112], as well as trophic factors to damaged diabetic kidney.…”

“…MSCs secrete a wide array of cytokines and growth factors, which can suppress the immune system, fibrosis oxidative stress, and apoptosis and enhance angiogenesis [35]. …”

“…To note, pharmacologic induction of DN with STZ, with or without accelerating factors, such as high fat diet, uninephrectomy, or use of the nonobese diabetic strain (NOD) strain has been the most common rodent model of DN to study the potential therapeutic of MSCs [35]. …”

Influence of Stem Cell Therapy on Thyroid Function and Reactive Oxygen Species Production in Diabetic Rats

“…Several studies have shown that MSC therapy can be useful for the treatment of complications associated with DM, including cardiovascular complications, diabetic kidney disease and diabetic retinopathy [4,[9][10][11]. However, to our knowledge, the impact of MSC therapy on thyroid H 2 O 2 generation and thyroid function in DM remains unknown.…”

Transplantation of induced mesenchymal stem cells for treating chronic renal insufficiency

“…Stem or progenitor cell therapies offer an alternative strategy for modulating complex disease processes by suppressing multiple pathogenic pathways and promoting pro-regenerative mechanisms. Mesenchymal stem cells (MSCs) have shown particular promise in this regard based on their availability from adult tissues and their diverse mechanisms of action, including secretion of paracrine anti-inflammatory and cytoprotective factors [2]. …”