Cell therapy using genome-engineered stem cells has emerged as a novel strategy for the treatment of
kidney diseases. By exploiting genome editing technology, human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) secreting an angiogenic factors or an anti-inflammatory factor were generated for therapeutic application in
acute kidney injury. Junction polymerase chain reaction analysis verified
zinc finger nucleases-assisted integration of the desired gene into the hUC-MSCs. Flow cytometry and differentiation assays indicated that genome editing did not affect the differentiation potential of these mesenchymal stem cells.
Protein measurement in
conditioned media with the use of ELISA and immunoblotting revealed the production and secretion of each integrated gene product. For
cell therapy in the bilateral
ischemia-reperfusion mouse model of
acute kidney injury, our innovative scaffold-free cell sheets were established using a non-biodegradable temperature-responsive
polymer. One of each type of scaffold-free cell sheets of either the
angiogenic factor vascular endothelial grown factor or
angiopoietin-1, or the anti-inflammatory factor
erythropoietin, or α-
melanocyte-stimulating hormone-secreting hUC-MSCs was applied to the decapsulated kidney surface. This resulted in significant amelioration of kidney dysfunction in the mice with
acute kidney injury, effects that were superior to
intravenous administration of the same genome-engineered hUC-MSCs. Thus, our scaffold-free cell sheets of genome-engineered mesenchymal stem cells provides
therapeutic effects by inhibiting
acute kidney injury via angiogenesis or anti-
inflammation.