TUDCA-treated chronic kidney disease-derived hMSCs improve therapeutic efficacy in ischemic disease via PrP(C)

Although autologous human mesenchymal stem cells (hMSCs) are a promising source for regenerative stem cell therapy in chronic kidney disease (CKD), the barriers associated with pathophysiological conditions limit therapeutic applicability to patients. We confirmed that level of cellular prion protein (PrP(C)) in serum was decreased and mitochondria function of CKD-derived hMSCs (CKD-hMSCs) was impaired in patients with CKD. We proved that treatment of CKD-hMSCs with tauroursodeoxycholic acid (TUDCA), a bile acid, enhanced the mitochondrial function of these cells through regulation of PINK1-PrP(C)-dependent pathway. In a murine hindlimb ischemia model with CKD, tail vein injection of TUDCA-treated CKD-hMSCs improved the functional recovery, including kidney recovery, limb salvage, blood perfusion ratio, and vessel formation along with restored expression of PrP(C) in the blood serum of the mice. These data suggest that TUDCA-treated CKD-hMSCs are a promising new autologous stem cell therapeutic intervention that dually treats cardiovascular problems and CKD in patients.