Biological Membrane-Packed Mesenchymal Stem Cells Treat Acute Kidney Disease by Ameliorating Mitochondrial-Related Apoptosis

Xiaodong Geng,Xiangmei Chen,Ou Li,Wei Zheng,Di Wu,Quan Hong,Weiwei Wang,Guangyan Cai

doi:10.1038/srep41136

Abstract

The mortality of rhabdomyolysis-induced AKI remains high because no effective therapy exists. We investigated a new therapeutic method using MSCs. The aim of this study was to investigate the therapeutic potential and anti-apoptotic mechanisms of action of MSCs in the treatment of AKI induced by glycerol in vivo and in vitro. We used Duragen as a biological membrane to pack MSCs on the glycerol-injured renal tissue in vivo. The anti-apoptotic mechanism was investigated. In vitro, HK-2 cells were incubated with ferrous myoglobin and MSCs-conditioned medium, followed by cell proliferation and apoptosis assays. We founded that packing MSCs on the injured renal tissue preserved renal function, ameliorated renal tubular lesions, and reduced apoptosis in the mice with glycerol-induced AKI. The MSC-conditioned medium improved HK-2 cell viability and inhibited apoptosis. These effects were reversed by the PI3K inhibitor LY294002. Biological membrane packing of MSCs on the renal tissue has a therapeutic rescue function by inhibiting cell apoptosis in vivo. MSCs protect renal cells from apoptosis induced by myoglobin in vitro. We have thus demonstrated MSCs reduced rhabdomyolysis-associated renal injury and cell apoptosis by activating the PI3K/Akt pathway and inhibiting apoptosis.

Highlights

Pro-apoptotic proteins such as Bad, caspase-3, and caspase-9 are involved in the process of apoptosis[11]
Duragen is a collagen matrix synthesized from bovine Achilles tendon
Glycerol administration resulted in significant increases in serum creatinine(Scr) and blood urea nitrogen(BUN) in the RM mice compared with the levels in the sham group

Summary

Introduction

Pro-apoptotic proteins such as Bad, caspase-3, and caspase-9 are involved in the process of apoptosis[11]. Its underlying mechanisms in MSC-treated glycerol-induced AKI remain poorly understood. Duragen is a collagen matrix synthesized from bovine Achilles tendon. It is a type of biological membrane(BM) that can be used to treat cerebrospinal fluid leaks[12]. We used Duragen as a biological membrane to wrap MSCs; it was packed on the injured kidney. This maneuver allowed us to permanently lodge MSCs into the injured kidney. We used HK-2 human renal proximal tubule cells co-cultured with ferrous myoglobinin vitro and a glycerol-induced mouse AKI model in vivo to further understand the mechanisms responsible for the renoprotective effects of MSCs

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