The Promise of Mesenchymal Stem Cell Therapy for Diabetic Kidney Disease
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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.
KeywordsDiabetes mellitus Diabetic nephropathy Stem cells Mesenchymal stem cells Inflammation
The authors are supported by grants from the European Commission [Horizon 2020 Collaborative Health Project NEPHSTROM (grant number 634086; TPG, WPM, NI, TO’B, MDG) and FP7 Collaborative Health Project VISICORT (grant number 602470; MDG)] and from Science Foundation Ireland [REMEDI Strategic Research Cluster (grant number 09/SRC-B1794; TO’B, MDG) and CÚRAM Research Centre (grant number 13/RC/2073; TO’B, MDG)] and by the European Regional Development Fund. TPG is supported by a Hardiman Scholarship from the College of Medicine, Nursing and Health Science of the National University of Ireland, Galway.
Compliance with Ethical Guidelines
Conflict of Interest
Tomás P. Griffin declares that he has no conflict of interest.
William Patrick Martin reports grant support from the European Commission.
Nahidul Islam reports grant support from the European Commission.
Timothy O’Brien reports grants from the European Commission, Science Foundation Ireland, and Medtronic. He reports other from the European Regional Development Fund, Orbsen Therapeutics and Onkimmune. He reports personal fees from Merck Sharp and Dohme, Sanofi Regeneron, Eli Lilly and Novo Nordisk.
Matthew D. Griffin reports grants from the European Commission, Science Foundation Ireland and Randox Teoranta; and other from the European Regional Development Fund,
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance, •• Of major importance
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