PMID- 32853632 OWN - NLM STAT- MEDLINE DCOM- 20210621 LR - 20210621 IS - 1523-1755 (Electronic) IS - 0085-2538 (Linking) VI - 99 IP - 1 DP - 2021 Jan TI - A nonbiodegradable scaffold-free cell sheet of genome-engineered mesenchymal stem cells inhibits development of acute kidney injury. PG - 117-133 LID - S0085-2538(20)30960-1 [pii] LID - 10.1016/j.kint.2020.07.043 [doi] AB - 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 alpha-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. CI - Copyright (c) 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved. FAU - Park, Hye-Jeong AU - Park HJ AD - Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Taegu, Korea; BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, School of Medicine, Kyungpook National University, Taegu, Korea. FAU - Kong, Min Jung AU - Kong MJ AD - BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, School of Medicine, Kyungpook National University, Taegu, Korea; Department of Anatomy, School of Medicine, Kyungpook National University, Taegu, Korea. FAU - Jang, Hyo-Ju AU - Jang HJ AD - Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Taegu, Korea; BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, School of Medicine, Kyungpook National University, Taegu, Korea. FAU - Cho, Jeong-In AU - Cho JI AD - Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Taegu, Korea; BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, School of Medicine, Kyungpook National University, Taegu, Korea. FAU - Park, Eui-Jung AU - Park EJ AD - Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Taegu, Korea; BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, School of Medicine, Kyungpook National University, Taegu, Korea. FAU - Lee, In-Kyu AU - Lee IK AD - BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, School of Medicine, Kyungpook National University, Taegu, Korea; Department of Internal Medicine, School of Medicine, Kyungpook National University, Taegu, Korea. FAU - Frokiaer, Jorgen AU - Frokiaer J AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. FAU - Norregaard, Rikke AU - Norregaard R AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. FAU - Park, Kwon Moo AU - Park KM AD - BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, School of Medicine, Kyungpook National University, Taegu, Korea; Department of Anatomy, School of Medicine, Kyungpook National University, Taegu, Korea. FAU - Kwon, Tae-Hwan AU - Kwon TH AD - Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Taegu, Korea; BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, School of Medicine, Kyungpook National University, Taegu, Korea. Electronic address: thkwon@knu.ac.kr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200824 PL - United States TA - Kidney Int JT - Kidney international JID - 0323470 SB - IM CIN - Kidney Int. 2021 Jan;99(1):22-24. PMID: 33390229 MH - *Acute Kidney Injury/genetics/therapy MH - Animals MH - Cell Differentiation MH - *Mesenchymal Stem Cell Transplantation MH - *Mesenchymal Stem Cells MH - Mice MH - Umbilical Cord OTO - NOTNLM OT - acute kidney injury OT - angiogenesis OT - anti-inflammation OT - genome editing OT - mesenchymal stem cells EDAT- 2020/08/28 06:00 MHDA- 2021/06/22 06:00 CRDT- 2020/08/28 06:00 PHST- 2020/02/26 00:00 [received] PHST- 2020/07/15 00:00 [revised] PHST- 2020/07/30 00:00 [accepted] PHST- 2020/08/28 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2020/08/28 06:00 [entrez] AID - S0085-2538(20)30960-1 [pii] AID - 10.1016/j.kint.2020.07.043 [doi] PST - ppublish SO - Kidney Int. 2021 Jan;99(1):117-133. doi: 10.1016/j.kint.2020.07.043. Epub 2020 Aug 24.