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

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A nonbiodegradable scaffold-free cell sheet of genome-engineered mesenchymal stem cells inhibits development of acute kidney injury. / Park, Hye Jeong; Kong, Min Jung; Jang, Hyo Ju; Cho, Jeong In; Park, Eui Jung; Lee, In Kyu; Frøkiær, Jørgen; Norregaard, Rikke; Park, Kwon Moo; Kwon, Tae Hwan.

In: Kidney International, Vol. 99, No. 1, 01.2021, p. 117-133.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Park, HJ, Kong, MJ, Jang, HJ, Cho, JI, Park, EJ, Lee, IK, Frøkiær, J, Norregaard, R, Park, KM & Kwon, TH 2021, 'A nonbiodegradable scaffold-free cell sheet of genome-engineered mesenchymal stem cells inhibits development of acute kidney injury', Kidney International, vol. 99, no. 1, pp. 117-133. https://doi.org/10.1016/j.kint.2020.07.043

APA

Park, H. J., Kong, M. J., Jang, H. J., Cho, J. I., Park, E. J., Lee, I. K., Frøkiær, J., Norregaard, R., Park, K. M., & Kwon, T. H. (2021). A nonbiodegradable scaffold-free cell sheet of genome-engineered mesenchymal stem cells inhibits development of acute kidney injury. Kidney International, 99(1), 117-133. https://doi.org/10.1016/j.kint.2020.07.043

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Author

Park, Hye Jeong ; Kong, Min Jung ; Jang, Hyo Ju ; Cho, Jeong In ; Park, Eui Jung ; Lee, In Kyu ; Frøkiær, Jørgen ; Norregaard, Rikke ; Park, Kwon Moo ; Kwon, Tae Hwan. / A nonbiodegradable scaffold-free cell sheet of genome-engineered mesenchymal stem cells inhibits development of acute kidney injury. In: Kidney International. 2021 ; Vol. 99, No. 1. pp. 117-133.

Bibtex

@article{a16cac7437ea4c1ba156ba599d5a4038,
title = "A nonbiodegradable scaffold-free cell sheet of genome-engineered mesenchymal stem cells inhibits development of acute kidney injury",
abstract = "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.",
keywords = "acute kidney injury, angiogenesis, anti-inflammation, genome editing, mesenchymal stem cells",
author = "Park, {Hye Jeong} and Kong, {Min Jung} and Jang, {Hyo Ju} and Cho, {Jeong In} and Park, {Eui Jung} and Lee, {In Kyu} and J{\o}rgen Fr{\o}ki{\ae}r and Rikke Norregaard and Park, {Kwon Moo} and Kwon, {Tae Hwan}",
year = "2021",
month = jan,
doi = "10.1016/j.kint.2020.07.043",
language = "English",
volume = "99",
pages = "117--133",
journal = "Kidney International. Supplement",
issn = "0098-6577",
publisher = "Wiley-Blackwell Publishing, Inc.",
number = "1",

}

RIS

TY - JOUR

T1 - A nonbiodegradable scaffold-free cell sheet of genome-engineered mesenchymal stem cells inhibits development of acute kidney injury

AU - Park, Hye Jeong

AU - Kong, Min Jung

AU - Jang, Hyo Ju

AU - Cho, Jeong In

AU - Park, Eui Jung

AU - Lee, In Kyu

AU - Frøkiær, Jørgen

AU - Norregaard, Rikke

AU - Park, Kwon Moo

AU - Kwon, Tae Hwan

PY - 2021/1

Y1 - 2021/1

N2 - 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.

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 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.

KW - acute kidney injury

KW - angiogenesis

KW - anti-inflammation

KW - genome editing

KW - mesenchymal stem cells

UR - http://www.scopus.com/inward/record.url?scp=85097766778&partnerID=8YFLogxK

U2 - 10.1016/j.kint.2020.07.043

DO - 10.1016/j.kint.2020.07.043

M3 - Journal article

C2 - 32853632

AN - SCOPUS:85097766778

VL - 99

SP - 117

EP - 133

JO - Kidney International. Supplement

JF - Kidney International. Supplement

SN - 0098-6577

IS - 1

ER -