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Differentiation Capacity of Porcine Skeletal Muscle-Derived Stem Cells as Intermediate Species between Mice and Humans

Large animal experiments are important for preclinical studies of regenerative stem cell transplantation therapy. Therefore, we investigated the differentiation capacity of pig skeletal muscle-derived stem cells (Sk-MSCs) as an intermediate model between mice and humans for nerve muscle regenerative...

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Autores principales: Tamaki, Tetsuro, Natsume, Toshiharu, Katoh, Akira, Nakajima, Nobuyuki, Saito, Kosuke, Fukuzawa, Tsuyoshi, Otake, Masayoshi, Enya, Satoko, Kangawa, Akihisa, Imai, Takeshi, Tamaki, Miyu, Uchiyama, Yoshiyasu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10297882/
https://www.ncbi.nlm.nih.gov/pubmed/37373009
http://dx.doi.org/10.3390/ijms24129862
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author Tamaki, Tetsuro
Natsume, Toshiharu
Katoh, Akira
Nakajima, Nobuyuki
Saito, Kosuke
Fukuzawa, Tsuyoshi
Otake, Masayoshi
Enya, Satoko
Kangawa, Akihisa
Imai, Takeshi
Tamaki, Miyu
Uchiyama, Yoshiyasu
author_facet Tamaki, Tetsuro
Natsume, Toshiharu
Katoh, Akira
Nakajima, Nobuyuki
Saito, Kosuke
Fukuzawa, Tsuyoshi
Otake, Masayoshi
Enya, Satoko
Kangawa, Akihisa
Imai, Takeshi
Tamaki, Miyu
Uchiyama, Yoshiyasu
author_sort Tamaki, Tetsuro
collection PubMed
description Large animal experiments are important for preclinical studies of regenerative stem cell transplantation therapy. Therefore, we investigated the differentiation capacity of pig skeletal muscle-derived stem cells (Sk-MSCs) as an intermediate model between mice and humans for nerve muscle regenerative therapy. Enzymatically extracted cells were obtained from green-fluorescence transgenic micro-mini pigs (GFP-Tg MMP) and sorted as CD34+/45− (Sk-34) and CD34−/45−/29+ (Sk-DN) fractions. The ability to differentiate into skeletal muscle, peripheral nerve, and vascular cell lineages was examined via in vitro cell culture and in vivo cell transplantation into the damaged tibialis anterior muscle and sciatic nerves of nude mice and rats. Protein and mRNA levels were analyzed using RT-PCR, immunohistochemistry, and immunoelectron microscopy. The myogenic potential, which was tested by Pax7 and MyoD expression and the formation of muscle fibers, was higher in Sk-DN cells than in Sk-34 cells but remained weak in the latter. In contrast, the capacity to differentiate into peripheral nerve and vascular cell lineages was significantly stronger in Sk-34 cells. In particular, Sk-DN cells did not engraft to the damaged nerve, whereas Sk-34 cells showed active engraftment and differentiation into perineurial/endoneurial cells, endothelial cells, and vascular smooth muscle cells, similar to the human case, as previously reported. Therefore, we concluded that Sk-34 and Sk-DN cells in pigs are closer to those in humans than to those in mice.
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spelling pubmed-102978822023-06-28 Differentiation Capacity of Porcine Skeletal Muscle-Derived Stem Cells as Intermediate Species between Mice and Humans Tamaki, Tetsuro Natsume, Toshiharu Katoh, Akira Nakajima, Nobuyuki Saito, Kosuke Fukuzawa, Tsuyoshi Otake, Masayoshi Enya, Satoko Kangawa, Akihisa Imai, Takeshi Tamaki, Miyu Uchiyama, Yoshiyasu Int J Mol Sci Article Large animal experiments are important for preclinical studies of regenerative stem cell transplantation therapy. Therefore, we investigated the differentiation capacity of pig skeletal muscle-derived stem cells (Sk-MSCs) as an intermediate model between mice and humans for nerve muscle regenerative therapy. Enzymatically extracted cells were obtained from green-fluorescence transgenic micro-mini pigs (GFP-Tg MMP) and sorted as CD34+/45− (Sk-34) and CD34−/45−/29+ (Sk-DN) fractions. The ability to differentiate into skeletal muscle, peripheral nerve, and vascular cell lineages was examined via in vitro cell culture and in vivo cell transplantation into the damaged tibialis anterior muscle and sciatic nerves of nude mice and rats. Protein and mRNA levels were analyzed using RT-PCR, immunohistochemistry, and immunoelectron microscopy. The myogenic potential, which was tested by Pax7 and MyoD expression and the formation of muscle fibers, was higher in Sk-DN cells than in Sk-34 cells but remained weak in the latter. In contrast, the capacity to differentiate into peripheral nerve and vascular cell lineages was significantly stronger in Sk-34 cells. In particular, Sk-DN cells did not engraft to the damaged nerve, whereas Sk-34 cells showed active engraftment and differentiation into perineurial/endoneurial cells, endothelial cells, and vascular smooth muscle cells, similar to the human case, as previously reported. Therefore, we concluded that Sk-34 and Sk-DN cells in pigs are closer to those in humans than to those in mice. MDPI 2023-06-07 /pmc/articles/PMC10297882/ /pubmed/37373009 http://dx.doi.org/10.3390/ijms24129862 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tamaki, Tetsuro
Natsume, Toshiharu
Katoh, Akira
Nakajima, Nobuyuki
Saito, Kosuke
Fukuzawa, Tsuyoshi
Otake, Masayoshi
Enya, Satoko
Kangawa, Akihisa
Imai, Takeshi
Tamaki, Miyu
Uchiyama, Yoshiyasu
Differentiation Capacity of Porcine Skeletal Muscle-Derived Stem Cells as Intermediate Species between Mice and Humans
title Differentiation Capacity of Porcine Skeletal Muscle-Derived Stem Cells as Intermediate Species between Mice and Humans
title_full Differentiation Capacity of Porcine Skeletal Muscle-Derived Stem Cells as Intermediate Species between Mice and Humans
title_fullStr Differentiation Capacity of Porcine Skeletal Muscle-Derived Stem Cells as Intermediate Species between Mice and Humans
title_full_unstemmed Differentiation Capacity of Porcine Skeletal Muscle-Derived Stem Cells as Intermediate Species between Mice and Humans
title_short Differentiation Capacity of Porcine Skeletal Muscle-Derived Stem Cells as Intermediate Species between Mice and Humans
title_sort differentiation capacity of porcine skeletal muscle-derived stem cells as intermediate species between mice and humans
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10297882/
https://www.ncbi.nlm.nih.gov/pubmed/37373009
http://dx.doi.org/10.3390/ijms24129862
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