Effects of Vitamin C on Cytotherapy-Mediated Muscle Regeneration

Skeletal muscles are the largest organs in the human body, and several therapeutic trials have been conducted that included stem cell transplantation to regenerate damaged or wasted muscles. It is well known that it is essential to make a favorable microenvironment (stem cell niche) to induce the pr...

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Main Authors: Ah-Young Kim, Eun-Mi Lee, Eun-Joo Lee, Chang-Woo Min, Kyung-Ku Kang, Jin-Kyu Park, Il-Hwa Hong, Akihito Ishigami, Jacques P. Tremblay, Kyu-Shik Jeong D.V.M., Ph.D.
Format: Article
Language:English
Published: SAGE Publishing 2013-10-01
Series:Cell Transplantation
Online Access:https://doi.org/10.3727/096368912X657846
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author Ah-Young Kim
Eun-Mi Lee
Eun-Joo Lee
Chang-Woo Min
Kyung-Ku Kang
Jin-Kyu Park
Il-Hwa Hong
Akihito Ishigami
Jacques P. Tremblay
Kyu-Shik Jeong D.V.M., Ph.D.
author_facet Ah-Young Kim
Eun-Mi Lee
Eun-Joo Lee
Chang-Woo Min
Kyung-Ku Kang
Jin-Kyu Park
Il-Hwa Hong
Akihito Ishigami
Jacques P. Tremblay
Kyu-Shik Jeong D.V.M., Ph.D.
author_sort Ah-Young Kim
collection DOAJ
description Skeletal muscles are the largest organs in the human body, and several therapeutic trials have been conducted that included stem cell transplantation to regenerate damaged or wasted muscles. It is well known that it is essential to make a favorable microenvironment (stem cell niche) to induce the proper differentiation of the transplanted stem cells. Some drugs, such as losartan (angiotensin II type I blocker), enhance the therapeutic effects of transplanted stem cells by inhibiting fibrosis. In this study, we hypothesized that another substance, vitamin C (ascorbic acid), might improve the niche for stem cell transplantation based on its potent antioxidant effects. In both gross and microscopic observations, vitamin C-depleted mice exhibited more incomplete regeneration of damaged muscles than those treated with vitamin C. Carbonylated protein groups, which are the end products of oxidative stress, were detected in all experimental groups; however, the vitamin C-depleted groups exhibited a more potent positive reaction than that of the vitamin C-supplied groups. The difference is clearer in the presence of transplanted stem cells. Moreover, the serum total vitamin C level and the ascorbic acid (AA) to dehydroascorbic acid (DHA) ratio also were decreased in the presence of transplanted adipose-derived stem cells (ASCs). Taken together, these data can be considered as proof of vitamin C utilization by cells in vivo. The vitamin C-supplied groups displayed more severe fibrosis than that of the vitamin C-depleted groups. Since vitamin C is a major cofactor for the collagen synthesis, its deficiency resulted in reduced fibrosis. In conclusion, we demonstrated that vitamin C not only has a positive effect on adjusting the stem cell niche to boost muscle regeneration but also has an adverse aspect due to its profibrotic effect.
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spelling doaj.art-252179add725417ba2ef6a89b7a70a012022-12-21T20:22:10ZengSAGE PublishingCell Transplantation0963-68971555-38922013-10-012210.3727/096368912X657846Effects of Vitamin C on Cytotherapy-Mediated Muscle RegenerationAh-Young Kim0Eun-Mi Lee1Eun-Joo Lee2Chang-Woo Min3Kyung-Ku Kang4Jin-Kyu Park5Il-Hwa Hong6Akihito Ishigami7Jacques P. Tremblay8Kyu-Shik Jeong D.V.M., Ph.D.9Stem Cell Therapeutic Research Institute, Kyungpook National University, Daegu, Republic of KoreaStem Cell Therapeutic Research Institute, Kyungpook National University, Daegu, Republic of KoreaStem Cell Therapeutic Research Institute, Kyungpook National University, Daegu, Republic of KoreaStem Cell Therapeutic Research Institute, Kyungpook National University, Daegu, Republic of KoreaStem Cell Therapeutic Research Institute, Kyungpook National University, Daegu, Republic of KoreaDepartment of Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu, Republic of KoreaDepartment of Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu, Republic of KoreaMolecular Regulation of Aging, Tokyo Metropolitan Institute of Gerontology, Tokyo, JapanDepartment of Neurosciences, CHUL Research Center, Quebec City, QC, CanadaStem Cell Therapeutic Research Institute, Kyungpook National University, Daegu, Republic of KoreaSkeletal muscles are the largest organs in the human body, and several therapeutic trials have been conducted that included stem cell transplantation to regenerate damaged or wasted muscles. It is well known that it is essential to make a favorable microenvironment (stem cell niche) to induce the proper differentiation of the transplanted stem cells. Some drugs, such as losartan (angiotensin II type I blocker), enhance the therapeutic effects of transplanted stem cells by inhibiting fibrosis. In this study, we hypothesized that another substance, vitamin C (ascorbic acid), might improve the niche for stem cell transplantation based on its potent antioxidant effects. In both gross and microscopic observations, vitamin C-depleted mice exhibited more incomplete regeneration of damaged muscles than those treated with vitamin C. Carbonylated protein groups, which are the end products of oxidative stress, were detected in all experimental groups; however, the vitamin C-depleted groups exhibited a more potent positive reaction than that of the vitamin C-supplied groups. The difference is clearer in the presence of transplanted stem cells. Moreover, the serum total vitamin C level and the ascorbic acid (AA) to dehydroascorbic acid (DHA) ratio also were decreased in the presence of transplanted adipose-derived stem cells (ASCs). Taken together, these data can be considered as proof of vitamin C utilization by cells in vivo. The vitamin C-supplied groups displayed more severe fibrosis than that of the vitamin C-depleted groups. Since vitamin C is a major cofactor for the collagen synthesis, its deficiency resulted in reduced fibrosis. In conclusion, we demonstrated that vitamin C not only has a positive effect on adjusting the stem cell niche to boost muscle regeneration but also has an adverse aspect due to its profibrotic effect.https://doi.org/10.3727/096368912X657846
spellingShingle Ah-Young Kim
Eun-Mi Lee
Eun-Joo Lee
Chang-Woo Min
Kyung-Ku Kang
Jin-Kyu Park
Il-Hwa Hong
Akihito Ishigami
Jacques P. Tremblay
Kyu-Shik Jeong D.V.M., Ph.D.
Effects of Vitamin C on Cytotherapy-Mediated Muscle Regeneration
Cell Transplantation
title Effects of Vitamin C on Cytotherapy-Mediated Muscle Regeneration
title_full Effects of Vitamin C on Cytotherapy-Mediated Muscle Regeneration
title_fullStr Effects of Vitamin C on Cytotherapy-Mediated Muscle Regeneration
title_full_unstemmed Effects of Vitamin C on Cytotherapy-Mediated Muscle Regeneration
title_short Effects of Vitamin C on Cytotherapy-Mediated Muscle Regeneration
title_sort effects of vitamin c on cytotherapy mediated muscle regeneration
url https://doi.org/10.3727/096368912X657846
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