在扩张型心肌病仓鼠模型中,脂肪来源的间充质干细胞通过ANT-1维持心脏功能。

Adipose-derived mesenchymal stem cells preserve cardiac function via ANT-1 in dilated cardiomyopathy hamster model.

作者信息

Mori Daisuke, Miyagawa Shigeru, Kido Takashi, Hata Hiroki, Ueno Takayoshi, Toda Koichi, Kuratani Toru, Oota Miwa, Kawai Kotoe, Kurata Hayato, Nishida Hiroyuki, Sawa Yoshiki

机构信息

Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Japan.

Institute of Advanced Stem Cell Therapy, Osaka University, Osaka, Japan.

出版信息

Regen Ther. 2021 Jul 9;18:182-190. doi: 10.1016/j.reth.2021.06.006. eCollection 2021 Dec.

Abstract

INTRODUCTION

Idiopathic dilated cardiomyopathy (DCM) is associated with abnormalities in cytoskeletal proteins, mitochondrial ATP transporter, microvasculature, and fibrosis. Mesenchymal stem cells (MSCs) can ameliorate distressed mitochondrial and structural proteins, as well as fibrosis, via the paracrine effect of cytokines. This study aimed to investigate whether the transplantation of adipose tissue-derived MSCs (ADSCs) reverses histological and functional abnormalities in the distressed myocardium of DCM-like hamsters by modulating the expression of adenine nucleotide translocase 1 (ANT-1).

METHODS

Eighteen weeks after birth, ADSCs were implanted onto the cardiac surface of δ-sarcoglycan (SG)-deficient hamsters or sham surgery was performed.

RESULTS

Left ventricular ejection fraction and end-systolic diameter were maintained in ADSC-treated animals for four weeks, ATP concentration was considerably elevated in the cardiomyocytes of these animals, and ANT-1 expression was significantly upregulated as well. The expression of extracellular matrix and myocardial cytoskeletal proteins, such as collagen, SG, and α-dystroglycan, did not differ between groups. However, significant improvements in myosin and Smad4 expression, cardiomyocyte hypertrophy, and capillary density occurred in the ADSC-treated group.

CONCLUSIONS

We demonstrated that ADSCs might maintain cardiac function in the DCM hamster model by enhancing ATP concentration, as well as mitochondrial transporter and myosin expression, indicating their potential for DCM treatment.

摘要

引言

特发性扩张型心肌病(DCM)与细胞骨架蛋白、线粒体ATP转运体、微血管系统及纤维化异常有关。间充质干细胞(MSCs)可通过细胞因子的旁分泌作用改善受损的线粒体和结构蛋白以及纤维化。本研究旨在探讨脂肪组织来源的间充质干细胞(ADSCs)移植是否通过调节腺嘌呤核苷酸转位酶1(ANT-1)的表达来逆转DCM样仓鼠受损心肌的组织学和功能异常。

方法

出生18周后,将ADSCs植入δ-肌聚糖(SG)缺陷型仓鼠的心脏表面或进行假手术。

结果

ADSC治疗组动物的左心室射血分数和收缩末期直径维持了四周,这些动物心肌细胞中的ATP浓度显著升高,ANT-1表达也明显上调。细胞外基质和心肌细胞骨架蛋白(如胶原蛋白、SG和α- dystroglycan)的表达在各组之间没有差异。然而,ADSC治疗组的肌球蛋白和Smad4表达、心肌细胞肥大和毛细血管密度有显著改善。

结论

我们证明,ADSCs可能通过提高ATP浓度以及线粒体转运体和肌球蛋白表达来维持DCM仓鼠模型的心脏功能,表明它们在治疗DCM方面具有潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/505f/8278151/b4c713dea9b5/gr1.jpg

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Dilated cardiomyopathy.

Lancet. 2017-2-10

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