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Ex vivo expansion of circulating CD34(+) cells enhances the regenerative effect on rat liver cirrhosis
Ex vivo expansion of autologous cells is indispensable for cell transplantation therapy of patients with liver cirrhosis. The aim of this study was to investigate the efficacy of human ex vivo-expanded CD34(+) cells for treatment of cirrhotic rat liver. Recipient rats were intraperitoneally injected...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4847556/ https://www.ncbi.nlm.nih.gov/pubmed/27162932 http://dx.doi.org/10.1038/mtm.2016.25 |
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author | Nakamura, Toru Koga, Hironori Iwamoto, Hideki Tsutsumi, Victor Imamura, Yasuko Naitou, Masako Masuda, Atsutaka Ikezono, Yu Abe, Mitsuhiko Wada, Fumitaka Sakaue, Takahiko Ueno, Takato Ii, Masaaki Alev, Cantas Kawamoto, Atsuhiko Asahara, Takayuki Torimura, Takuji |
author_facet | Nakamura, Toru Koga, Hironori Iwamoto, Hideki Tsutsumi, Victor Imamura, Yasuko Naitou, Masako Masuda, Atsutaka Ikezono, Yu Abe, Mitsuhiko Wada, Fumitaka Sakaue, Takahiko Ueno, Takato Ii, Masaaki Alev, Cantas Kawamoto, Atsuhiko Asahara, Takayuki Torimura, Takuji |
author_sort | Nakamura, Toru |
collection | PubMed |
description | Ex vivo expansion of autologous cells is indispensable for cell transplantation therapy of patients with liver cirrhosis. The aim of this study was to investigate the efficacy of human ex vivo-expanded CD34(+) cells for treatment of cirrhotic rat liver. Recipient rats were intraperitoneally injected with CCl(4) twice weekly for 3 weeks before administration of CD34(+) cells. CCl(4) was then re-administered twice weekly for 3 more weeks, and the rats were sacrificed. Saline, nonexpanded or expanded CD34(+) cells were injected via the spleen. After 7 days, CD34(+) cells were effectively expanded in a serum-free culture medium. Expanded CD34(+) cells were also increasingly positive for cell surface markers of VE-cadherin, VEGF receptor-2, and Tie-2. The expression of proangiogenic growth factors and adhesion molecules in expanded CD34(+) cells increased compared with nonexpanded CD34(+) cells. Expanded CD34(+) cell transplantation reduced liver fibrosis, with a decrease of αSMA(+) cells. Assessments of hepatocyte and sinusoidal endothelial cell proliferative activity indicated the superior potency of expanded CD34(+) cells over non-expanded CD34(+) cells. The inhibition of integrin αvβ3 and αvβ5 disturbed the engraftment of transplanted CD34(+) cells and aggravated liver fibrosis. These findings suggest that expanded CD34(+) cells enhanced the preventive efficacy of cell transplantation in a cirrhotic model. |
format | Online Article Text |
id | pubmed-4847556 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-48475562016-05-09 Ex vivo expansion of circulating CD34(+) cells enhances the regenerative effect on rat liver cirrhosis Nakamura, Toru Koga, Hironori Iwamoto, Hideki Tsutsumi, Victor Imamura, Yasuko Naitou, Masako Masuda, Atsutaka Ikezono, Yu Abe, Mitsuhiko Wada, Fumitaka Sakaue, Takahiko Ueno, Takato Ii, Masaaki Alev, Cantas Kawamoto, Atsuhiko Asahara, Takayuki Torimura, Takuji Mol Ther Methods Clin Dev Article Ex vivo expansion of autologous cells is indispensable for cell transplantation therapy of patients with liver cirrhosis. The aim of this study was to investigate the efficacy of human ex vivo-expanded CD34(+) cells for treatment of cirrhotic rat liver. Recipient rats were intraperitoneally injected with CCl(4) twice weekly for 3 weeks before administration of CD34(+) cells. CCl(4) was then re-administered twice weekly for 3 more weeks, and the rats were sacrificed. Saline, nonexpanded or expanded CD34(+) cells were injected via the spleen. After 7 days, CD34(+) cells were effectively expanded in a serum-free culture medium. Expanded CD34(+) cells were also increasingly positive for cell surface markers of VE-cadherin, VEGF receptor-2, and Tie-2. The expression of proangiogenic growth factors and adhesion molecules in expanded CD34(+) cells increased compared with nonexpanded CD34(+) cells. Expanded CD34(+) cell transplantation reduced liver fibrosis, with a decrease of αSMA(+) cells. Assessments of hepatocyte and sinusoidal endothelial cell proliferative activity indicated the superior potency of expanded CD34(+) cells over non-expanded CD34(+) cells. The inhibition of integrin αvβ3 and αvβ5 disturbed the engraftment of transplanted CD34(+) cells and aggravated liver fibrosis. These findings suggest that expanded CD34(+) cells enhanced the preventive efficacy of cell transplantation in a cirrhotic model. Nature Publishing Group 2016-04-27 /pmc/articles/PMC4847556/ /pubmed/27162932 http://dx.doi.org/10.1038/mtm.2016.25 Text en Copyright © 2016 Official journal of the American Society of Gene & Cell Therapy http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Nakamura, Toru Koga, Hironori Iwamoto, Hideki Tsutsumi, Victor Imamura, Yasuko Naitou, Masako Masuda, Atsutaka Ikezono, Yu Abe, Mitsuhiko Wada, Fumitaka Sakaue, Takahiko Ueno, Takato Ii, Masaaki Alev, Cantas Kawamoto, Atsuhiko Asahara, Takayuki Torimura, Takuji Ex vivo expansion of circulating CD34(+) cells enhances the regenerative effect on rat liver cirrhosis |
title | Ex vivo expansion of circulating CD34(+) cells enhances the regenerative effect on rat liver cirrhosis |
title_full | Ex vivo expansion of circulating CD34(+) cells enhances the regenerative effect on rat liver cirrhosis |
title_fullStr | Ex vivo expansion of circulating CD34(+) cells enhances the regenerative effect on rat liver cirrhosis |
title_full_unstemmed | Ex vivo expansion of circulating CD34(+) cells enhances the regenerative effect on rat liver cirrhosis |
title_short | Ex vivo expansion of circulating CD34(+) cells enhances the regenerative effect on rat liver cirrhosis |
title_sort | ex vivo expansion of circulating cd34(+) cells enhances the regenerative effect on rat liver cirrhosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4847556/ https://www.ncbi.nlm.nih.gov/pubmed/27162932 http://dx.doi.org/10.1038/mtm.2016.25 |
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