Infusion of mesenchymal stem cells overexpressing GDNF ameliorates renal function in nephrotoxic serum nephritis

Abstract

Nephrotoxic serum nephritis (NSN) is a well-established animal model of glomerulonephritis, a frequent clinical condition with a high mortality rate owing to the ineffectiveness of current therapies. Mesenchymal stem cells (MSCs) are adult stem cells with potential as novel therapies in regenerative medicine owing to the absence of allogenic rejection. Glial cell-derived neurotrophic factor (GDNF) acts as a morphogen in kidney development. The therapeutic effectiveness of bone marrow MSCs overexpressing GDNF (GDNF-MSCs) was evaluated in an NSN rat model. An adenoviral vector was used to transduce MSCs with GDNF and a green fluorescent protein reporter gene. Then, GDNF-MSCs were injected into NSN rats via the renal artery. The influence of GDNF on renal injury was assessed. The location of GDNF-MSCs in kidneys was detected using fluorescence microscopy, cells were counted, and kidney function was measured. Infusion of GNDF-MSCs enhanced the recovery of renal function in NSN rats. MSCs were detected in the kidney cortex after injection. Compared with control MSCs, GDNF-MSCs led to significantly better renal function and injury recovery in NSN rats. GDNF has a positive effect on MSC differentiation in renal tissue. Owing to their highly renoprotective capacity, GDNF-MSCs represent a possible novel cell-based paradigm for treatment of glomerulonephritis.

What is new in the management of rapidly progressive glomerulonephritis?

“…Stem cell therapy is at an early phase of development, but it may offer a future therapeutic strategy in immune-mediated renal disease (reviewed in [ 71 ]). There is some experimental evidence in animal models of anti-GBM disease, where investigators have used mesenchymal stem cells, which are progenitors of renal tissue, with some success [ 72 – 74 ]. A case of NCGN due to MPA successfully treated with stem cell therapy has been reported [ 75 ].…”

Mesenchymal stromal SB623 cell implantation mitigates nigrostriatal dopaminergic damage in a mouse model of Parkinson's disease

“…For example, striatal administration of GDNF has been previously associated with improved dopaminergic survival in animal models of PD (Choi‐Lundberg et al ., ; Rosenblad et al ., ; Smith and Cass, ; Madhavan et al ., ). MSCs releasing GDNF have been linked to protection in several models (Kurozumi et al ., ; Shi et al ., ; Glavaski‐Joksimovic et al ., ; Huang et al ., ; Whone et al ., ; Marconi et al ., ). Importantly, the involvement of other protective trophic factors released from SB263 cells and/or induction of glial support must be acknowledged.…”

Genetic Engineering as a Strategy to Improve the Therapeutic Efficacy of Mesenchymal Stem/Stromal Cells in Regenerative Medicine

“…CXCR4-MSCs had a 3-fold increase in cell migration capacity in vitro and in vivo in a myocardial infarct model when compared to control MSCs, correlating with an increased expression of metalloproteinases. Additionally, a 4-fold increase in capillary density was found in the hearts of animals treated with CXCR4-MSCs when compared to control MSCs groups (Huang Z. Y. et al, 2012). A significant improvement in cardiac function in CXCR4-MSCs treated animals compared to those treated with control MSCs, which may be explained by the reduction of heart fibrosis and increased angiogenesis post-injury (Huang W. et al, 2012;Mayorga et al, 2017;.…”