Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Differentiation Capacity of Porcine Skeletal Muscle-Derived Stem Cells As Intermediate Species Between Mice and Humans

Tetsuro Tamaki
* ORCID logo ,
Toshiharu Natsume
,
Akira Kato
,
Nobuyuki Nakajima
ORCID logo ,
Kosuke Saito
,
Tsuyoshi Fukuzawa
,
Masayoshi Otake
,
Satoko Enya
,
Akihisa Kangawa
,
Takeshi Imai
,
Miyu Tamaki
,
Yoshiyasu Uchiyama
ORCID logo
Version 1 : Received: 11 May 2023 / Approved: 12 May 2023 / Online: 12 May 2023 (11:18:40 CEST)

A peer-reviewed article of this Preprint also exists.

Tamaki, T.; Natsume, T.; Katoh, A.; Nakajima, N.; Saito, K.; Fukuzawa, T.; Otake, M.; Enya, S.; Kangawa, A.; Imai, T.; Tamaki, M.; Uchiyama, Y. Differentiation Capacity of Porcine Skeletal Muscle-Derived Stem Cells as Intermediate Species between Mice and Humans. Int. J. Mol. Sci. 2023, 24, 9862. Tamaki, T.; Natsume, T.; Katoh, A.; Nakajima, N.; Saito, K.; Fukuzawa, T.; Otake, M.; Enya, S.; Kangawa, A.; Imai, T.; Tamaki, M.; Uchiyama, Y. Differentiation Capacity of Porcine Skeletal Muscle-Derived Stem Cells as Intermediate Species between Mice and Humans. Int. J. Mol. Sci. 2023, 24, 9862.

Abstract

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 by 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 totally 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 were closer to those in humans than to those in mice.

Keywords

micro-mini pig; large animal experiment; GFP-transgenic pig; multipotent stem cells; skeletal muscle; nerve-muscle regeneration.

Subject

Biology and Life Sciences, Cell and Developmental Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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