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Phase I clinical study of liver regenerative therapy for cirrhosis by intrahepatic arterial infusion of freshly isolated autologous adipose tissue-derived stromal/stem (regenerative) cell

INTRODUCTION: Adipose tissue stromal cells contain a substantial number of mesenchymal stem cells. As such, their application to regeneration of miscellaneous impaired organs has attracted much attention. METHODS: We designed a clinical study to investigate freshly isolated autologous adipose tissue...

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Autores principales: Sakai, Yoshio, Takamura, Masayuki, Seki, Akihiro, Sunagozaka, Hajime, Terashima, Takeshi, Komura, Takuya, Yamato, Masatoshi, Miyazawa, Masaki, Kawaguchi, Kazunori, Nasti, Alessandro, Mochida, Hatsune, Usui, Soichiro, Otani, Nobuhisa, Ochiya, Takahiro, Wada, Takashi, Honda, Masao, Kaneko, Shuichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Japanese Society for Regenerative Medicine 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6134901/
https://www.ncbi.nlm.nih.gov/pubmed/30271839
http://dx.doi.org/10.1016/j.reth.2016.12.001
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author Sakai, Yoshio
Takamura, Masayuki
Seki, Akihiro
Sunagozaka, Hajime
Terashima, Takeshi
Komura, Takuya
Yamato, Masatoshi
Miyazawa, Masaki
Kawaguchi, Kazunori
Nasti, Alessandro
Mochida, Hatsune
Usui, Soichiro
Otani, Nobuhisa
Ochiya, Takahiro
Wada, Takashi
Honda, Masao
Kaneko, Shuichi
author_facet Sakai, Yoshio
Takamura, Masayuki
Seki, Akihiro
Sunagozaka, Hajime
Terashima, Takeshi
Komura, Takuya
Yamato, Masatoshi
Miyazawa, Masaki
Kawaguchi, Kazunori
Nasti, Alessandro
Mochida, Hatsune
Usui, Soichiro
Otani, Nobuhisa
Ochiya, Takahiro
Wada, Takashi
Honda, Masao
Kaneko, Shuichi
author_sort Sakai, Yoshio
collection PubMed
description INTRODUCTION: Adipose tissue stromal cells contain a substantial number of mesenchymal stem cells. As such, their application to regeneration of miscellaneous impaired organs has attracted much attention. METHODS: We designed a clinical study to investigate freshly isolated autologous adipose tissue-derived stromal/stem (regenerative) cell (ADRC) therapy for liver cirrhosis and conducted treatment in four cirrhotic patients. ADRCs were isolated from autologous subcutaneous adipose tissue obtained by the liposuction method, followed with use of the Celution system adipose tissue dissociation device. The primary endpoint is assessment of safety one month after treatment. We also characterized the obtained ADRCs. RESULTS: Two patients had type C cirrhosis, one had nonalcoholic steatohepatitis-cirrhosis, and one had type B cirrhosis. No serious adverse events were observed during the 1-month study period after freshly isolated ADRC infusion. Serum albumin concentrations were maintained or improved during this period as well as during the succeeding follow-up of approximately 1 year in two patients and 6 months in another patient. Liver regeneration-related factors, namely hepatocyte growth factor and interleukin-6, were elevated 1 day after ADRC treatment in all patients. The obtained freshly isolated ADRCs were expanded in culture and found to express mesenchymal stem cell markers. Gene expression profile analysis of ADRCs was shown to involve inflammatory features, suggesting that characteristics of the obtained ADRCs were related to immunomodulatory biological effects. CONCLUSION: This clinical study treatment for liver cirrhosis using ADRCs was proven to be safely conductible, and can be further investigated in future for regeneration/repair of liver cirrhosis.
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spelling pubmed-61349012018-09-28 Phase I clinical study of liver regenerative therapy for cirrhosis by intrahepatic arterial infusion of freshly isolated autologous adipose tissue-derived stromal/stem (regenerative) cell Sakai, Yoshio Takamura, Masayuki Seki, Akihiro Sunagozaka, Hajime Terashima, Takeshi Komura, Takuya Yamato, Masatoshi Miyazawa, Masaki Kawaguchi, Kazunori Nasti, Alessandro Mochida, Hatsune Usui, Soichiro Otani, Nobuhisa Ochiya, Takahiro Wada, Takashi Honda, Masao Kaneko, Shuichi Regen Ther Original Article INTRODUCTION: Adipose tissue stromal cells contain a substantial number of mesenchymal stem cells. As such, their application to regeneration of miscellaneous impaired organs has attracted much attention. METHODS: We designed a clinical study to investigate freshly isolated autologous adipose tissue-derived stromal/stem (regenerative) cell (ADRC) therapy for liver cirrhosis and conducted treatment in four cirrhotic patients. ADRCs were isolated from autologous subcutaneous adipose tissue obtained by the liposuction method, followed with use of the Celution system adipose tissue dissociation device. The primary endpoint is assessment of safety one month after treatment. We also characterized the obtained ADRCs. RESULTS: Two patients had type C cirrhosis, one had nonalcoholic steatohepatitis-cirrhosis, and one had type B cirrhosis. No serious adverse events were observed during the 1-month study period after freshly isolated ADRC infusion. Serum albumin concentrations were maintained or improved during this period as well as during the succeeding follow-up of approximately 1 year in two patients and 6 months in another patient. Liver regeneration-related factors, namely hepatocyte growth factor and interleukin-6, were elevated 1 day after ADRC treatment in all patients. The obtained freshly isolated ADRCs were expanded in culture and found to express mesenchymal stem cell markers. Gene expression profile analysis of ADRCs was shown to involve inflammatory features, suggesting that characteristics of the obtained ADRCs were related to immunomodulatory biological effects. CONCLUSION: This clinical study treatment for liver cirrhosis using ADRCs was proven to be safely conductible, and can be further investigated in future for regeneration/repair of liver cirrhosis. Japanese Society for Regenerative Medicine 2017-03-09 /pmc/articles/PMC6134901/ /pubmed/30271839 http://dx.doi.org/10.1016/j.reth.2016.12.001 Text en © 2017, The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Sakai, Yoshio
Takamura, Masayuki
Seki, Akihiro
Sunagozaka, Hajime
Terashima, Takeshi
Komura, Takuya
Yamato, Masatoshi
Miyazawa, Masaki
Kawaguchi, Kazunori
Nasti, Alessandro
Mochida, Hatsune
Usui, Soichiro
Otani, Nobuhisa
Ochiya, Takahiro
Wada, Takashi
Honda, Masao
Kaneko, Shuichi
Phase I clinical study of liver regenerative therapy for cirrhosis by intrahepatic arterial infusion of freshly isolated autologous adipose tissue-derived stromal/stem (regenerative) cell
title Phase I clinical study of liver regenerative therapy for cirrhosis by intrahepatic arterial infusion of freshly isolated autologous adipose tissue-derived stromal/stem (regenerative) cell
title_full Phase I clinical study of liver regenerative therapy for cirrhosis by intrahepatic arterial infusion of freshly isolated autologous adipose tissue-derived stromal/stem (regenerative) cell
title_fullStr Phase I clinical study of liver regenerative therapy for cirrhosis by intrahepatic arterial infusion of freshly isolated autologous adipose tissue-derived stromal/stem (regenerative) cell
title_full_unstemmed Phase I clinical study of liver regenerative therapy for cirrhosis by intrahepatic arterial infusion of freshly isolated autologous adipose tissue-derived stromal/stem (regenerative) cell
title_short Phase I clinical study of liver regenerative therapy for cirrhosis by intrahepatic arterial infusion of freshly isolated autologous adipose tissue-derived stromal/stem (regenerative) cell
title_sort phase i clinical study of liver regenerative therapy for cirrhosis by intrahepatic arterial infusion of freshly isolated autologous adipose tissue-derived stromal/stem (regenerative) cell
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6134901/
https://www.ncbi.nlm.nih.gov/pubmed/30271839
http://dx.doi.org/10.1016/j.reth.2016.12.001
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