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Abstract: TH-PO637

Mesenchymal Stem Cells Derived from Induced Pluripotent Stem Cells and Bone Marrow Are Equally Effective in Ameliorating Lipotoxicity-Induced Kidney Injury

Session Information

Category: Development, Stem Cells, and Regenerative Medicine

  • 501 Development, Stem Cells, and Regenerative Medicine: Basic

Authors

  • Li, Bin, The University of Hong Kong, Hong Kong, China
  • Leung, Joseph C K, The University of Hong Kong, Hong Kong, China
  • Chan, Loretta Y.Y., The University of Hong Kong, Hong Kong, China
  • Yiu, Wai Han, The University of Hong Kong, Hong Kong, China
  • Lai, Kar Neng, The University of Hong Kong, Hong Kong, China
  • Tang, Sydney C.W., The University of Hong Kong, Hong Kong, China
Background

Human induced pluripotent stem cell-derived mesenchymal stem cells (iPS-MSCs) are promising as an alternative to bone marrow-derived mesenchymal stem cells (BM-MSCs) for cell-based therapy. Lipotoxicity is an important pathogenetic factor leading to chronic kidney injury. This study aims to compare the therapeutic effects of iPS-MSCs and BM-MSCs in ameliorating lipotoxicity-induced kidney lesions.

Methods

Mice (C57BL/6J) fed normal diet (ND; 10 kcal%) or high-fat diet (HFD; 60 kcal%) for 12 weeks were randomly divided into vehicle control, iPS-MSC and BM-MSC subgroups (n=8 in each group), followed by infusion of saline or MSCs via tail vein and fed for further 8 weeks before sacrifice. Body weight, blood glucose and urine albumin were monitored throughout the experiment. Renal histological changes were assessed by Periodic acid-Schiff staining. Renal endoplasmic reticulum (ER) stress, inflammation and apoptosis were evaluated by real-time quantitative PCR, Western blot and TUNEL assay.

Results

Compared to ND group, mice fed HFD had significantly increased (1) body weight, blood glucose and urine albumin; (2) tubular injury score (tubular vacuolation and tubular glycogenated nuclei), glomerular size and mesangial expansion; (3) expression of markers for ER stress (BiP, p-eIF2α, ATF4, p-IRE1α, CHOP) and related phosphorylated signaling molecules (p-NF-κB, p-ERK, p-JNK); (4) expression of pro-inflammation mediators (IL-6, Cxcl1, Cxcl2) and (5) apoptosis (Bax/Bcl2 ratio and number of renal TUNEL-positive apoptotic cells). All these events were significantly attenuated by infusion with iPS-MSCs or BM-MSCs to the HFD-fed mice. Notably, iPS-MSCs and BM-MSCs infusion to HFD-fed mice have equivalent efficacy in ameliorating all the above-mentioned readouts in HFD-induced kidney injury.

Conclusion

Our study suggests comparable capability of iPS-MSCs and BM-MSCs in ameliorating lipotoxicity-induced kidney injury, supporting iPS-MSCs as a valuable alterative source to BM-MSCs for therapeutic application. (Funding: Health and Medical Research Fund Advance Medical Research Ref. #03143726 and Mrs. Rita T. Liu SBS of L & T Charitable Foundation Ltd)

Funding

  • Private Foundation Support