You are here

| Mesenchymal Stem Cells

Assessing iPSC-derived MSCs as a Therapeutic Approach to Obesity‐Associated Kidney Injury

Review of “Amelioration of Endoplasmic Reticulum Stress by Mesenchymal Stem Cells via Hepatocyte Growth Factor/c‐Met Signaling in Obesity‐Associated Kidney Injury” from STEM CELLS Translational Medicine by Stuart P. Atkinson

Researchers led by Sydney C.W. Tang (University of Hong Kong, Hong Kong, China) recently established treatment with mesenchymal stem cells derived from induced pluripotent stem cells (iPSC-MSCs) as an effective means to protect against chemotherapy-induced kidney disease [1]. Given the relevance of obesity as a current public health problem, the authors hoped that iPSC-derived MSCs might also represent a means to treat obesity‐related kidney injury [2] caused by the accumulation of free fatty acids [3, 4] and the induction of endoplasmic reticulum stress [4].

The team now returns with a new STEM CELLS Translational Medicine article in which the authors describe the therapeutic potential of iPSC-derived MSCs in a mouse model of obesity‐induced kidney injury and compare this approach with bone marrow-derived MSC treatment in the hope of elucidating the underlying regulatory mechanisms [5].

Li et al. evaluated MSC treatment in two obesity model systems: a palmitic acid-induced lipotoxic kidney injury model in renal tubular cells and mice fed a high-fat diet. Encouragingly, the authors discovered that treatment with either iPSC‐ or BM‐derived MSCs reduced endoplasmic reticulum stress, inflammation, and apoptosis in both model systems with equivalent efficacy. 

Further evaluations suggested that MSCs functioned by inducing the activation of HGF/c‐Met paracrine signaling in the obese kidney microenvironment that enhanced HGF and c‐Met secretion from glomerular endothelial cells and tubular cells, respectively. The authors confirmed these findings by showing how glomerular endothelial cell-derived or exogenous recombinant HGF counteracted palmitic acid-induced endoplasmic reticulum stress in cultured renal tubular cells, and how a neutralizing anti‐HGF antibody blocked this effect.

Overall, this new study provides evidence of the utility of MSCs in the treatment of lipotoxicity‐induced chronic kidney injury, the therapeutic equivalence of iPSC- and BM-derived MSCs, and the induction of the HGF/c‐Met signaling pathway as the therapeutic mechanism. Together, the authors hope that this data will provide the impetus for the application of iPSC-derived MSCs as a novel therapeutic approach to obesity‐associated kidney injury.

For more on the potential of iPSC-MSCs and novel approaches for the treatment of obesity-associated kidney injury, stay tuned to the Stem Cells Portal!

References

  1. Wu HJ, Yiu WH, Wong DWL, et al., Human induced pluripotent stem cell-derived mesenchymal stem cells prevent adriamycin nephropathy in mice. Oncotarget 2017;8:103640-103656.
  2. Ng M, Fleming T, Robinson M, et al., Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2014;384:766-81.
  3. Tanaka Y, Kume S, Araki S-i, et al., Fenofibrate, a PPARα agonist, has renoprotective effects in mice by enhancing renal lipolysis. Kidney International 2011;79:871-882.
  4. Szeto HH, Liu S, Soong Y, et al., Protection of mitochondria prevents high-fat diet-induced glomerulopathy and proximal tubular injury. Kidney International 2016;90:997-1011.
  5. Li B, Leung JCK, Chan LYY, et al., Amelioration of Endoplasmic Reticulum Stress by Mesenchymal Stem Cells via Hepatocyte Growth Factor/c-Met Signaling in Obesity-Associated Kidney Injury. STEM CELLS Translational Medicine 2019;8:898-910.