A nonbiodegradable scaffold-free cell sheet of genome-engineered mesenchymal stem cells inhibits development of acute kidney injury

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

DOI

  • Hye Jeong Park, Kyungpook National University
  • ,
  • Min Jung Kong, Kyungpook National University
  • ,
  • Hyo Ju Jang, Kyungpook National University
  • ,
  • Jeong In Cho, Kyungpook National University
  • ,
  • Eui Jung Park, Kyungpook National University
  • ,
  • In Kyu Lee, Kyungpook National University
  • ,
  • Jørgen Frøkiær
  • Rikke Norregaard
  • Kwon Moo Park, Kyungpook National University
  • ,
  • Tae Hwan Kwon, Kyungpook National University

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.

OriginalsprogEngelsk
BogserieKidney International
Vol/bind99
Nummer1
Sider (fra-til)117-133
Antal sider17
ISSN0085-2538
DOI
StatusUdgivet - jan. 2021

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