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微泡可增强人糖尿病脂肪组织来源间充质干细胞在体外的迁移能力,并改善体内伤口愈合情况。

Microvesicles enhance the mobility of human diabetic adipose tissue-derived mesenchymal stem cells in vitro and improve wound healing in vivo.

作者信息

Trinh Nhu Thuy, Yamashita Toshiharu, Tu Tran Cam, Kato Toshiki, Ohneda Kinuko, Sato Fujio, Ohneda Osamu

机构信息

Graduate School of Comprehensive Human Science, Laboratory of Regenerative Medicine and Stem Cell Biology, University of Tsukuba, Tsukuba 305-8575, Japan.

Laboratory of Molecular Pathophysiology, Faculty of Pharmacy, Takasaki University of Health and Welfare, Takasaki 370-0033, Japan.

出版信息

Biochem Biophys Res Commun. 2016 May 13;473(4):1111-1118. doi: 10.1016/j.bbrc.2016.04.025. Epub 2016 Apr 7.


DOI:10.1016/j.bbrc.2016.04.025
PMID:27063802
Abstract

Microvesicles (MVs) derived from mesenchymal stem cells showed the ability to alter the cell phenotype and function. We previously demonstrated that type 2 diabetic adipose tissue-derived mesenchymal stem cells (dAT-MSCs) increase in cell aggregation and adhesion in vitro and impair wound healing in vivo. However, the characterization and function of MVs derived from human non-diabetic AT-MSCs (nAT-MSCs) remain unknown. In this study, we characterized nAT-MSC-derived MVs and their function after the transfection of dAT-MSCs with MVs using the scratch assay and a flap mouse model. We found that human nAT-MSC-derived MVs expressed MSC-surface markers and improved dAT-MSC functions by altering the expression of genes associated with cell migration, survival, inflammation, and angiogenesis as well as miR29c and miR150. Remarkably, the transfection of dAT-MSCs with nAT-MSC-derived MVs improved their migration ability in vitro and wound healing ability in a flap mouse model. These results demonstrate a promising opportunity to modify the function of dAT-MSCs for therapeutic stem cell application in diabetic patients.

摘要

源自间充质干细胞的微泡(MVs)显示出改变细胞表型和功能的能力。我们之前证明,2型糖尿病脂肪组织来源的间充质干细胞(dAT-MSCs)在体外细胞聚集和黏附增加,在体内损害伤口愈合。然而,源自人非糖尿病脂肪组织间充质干细胞(nAT-MSCs)的MVs的特性和功能仍不清楚。在本研究中,我们使用划痕试验和皮瓣小鼠模型,对nAT-MSC来源的MVs及其在用MVs转染dAT-MSCs后的功能进行了表征。我们发现,人nAT-MSC来源的MVs表达间充质干细胞表面标志物,并通过改变与细胞迁移、存活、炎症和血管生成以及miR29c和miR150相关的基因表达来改善dAT-MSC的功能。值得注意的是,用nAT-MSC来源的MVs转染dAT-MSCs可提高其在体外的迁移能力和在皮瓣小鼠模型中的伤口愈合能力。这些结果表明,在糖尿病患者中修饰dAT-MSCs的功能以用于治疗性干细胞应用具有广阔前景。

相似文献

[1]
Microvesicles enhance the mobility of human diabetic adipose tissue-derived mesenchymal stem cells in vitro and improve wound healing in vivo.

Biochem Biophys Res Commun. 2016-5-13

[2]
Increased Expression of EGR-1 in Diabetic Human Adipose Tissue-Derived Mesenchymal Stem Cells Reduces Their Wound Healing Capacity.

Stem Cells Dev. 2016-5-15

[3]
Therapeutic Effects of Human Mesenchymal Stem Cell-derived Microvesicles in Severe Pneumonia in Mice.

Am J Respir Crit Care Med. 2015-8-1

[4]
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Stem Cell Res Ther. 2015-5-22

[5]
Erythropoietin-activated mesenchymal stem cells promote healing ulcers by improving microenvironment.

J Surg Res. 2016-10

[6]
Differentially expressed microRNAs in bone marrow mesenchymal stem cell-derived microvesicles in young and older rats and their effect on tumor growth factor-β1-mediated epithelial-mesenchymal transition in HK2 cells.

Stem Cell Res Ther. 2015-9-28

[7]
Microvesicles derived from Alde-Low EPCs support the wound healing capacity of AT-MSCs.

Biochem Biophys Res Commun. 2016-8-12

[8]
Effects of human umbilical cord blood-derived mesenchymal stromal cells and dermal fibroblasts on diabetic wound healing.

Cytotherapy. 2017-7

[9]
In vitro characterization of human hair follicle dermal sheath mesenchymal stromal cells and their potential in enhancing diabetic wound healing.

Cytotherapy. 2015-8

[10]
Spheroid Mesenchymal Stem Cells and Mesenchymal Stem Cell-Derived Microvesicles: Two Potential Therapeutic Strategies.

Stem Cells Dev. 2016-2-1

引用本文的文献

[1]
Synergistic effect of metformin and vitamin D on osteogenic differentiation of human adipose tissue-derived mesenchymal stem cells under high d-glucose conditions.

Regen Ther. 2023-12-26

[2]
Transformed extracellular vesicles with high angiogenic ability as therapeutics of distal ischemic tissues.

Front Cell Dev Biol. 2022-8-31

[3]
Adipose Tissue-Derived Mesenchymal Stem/Stromal Cells and Their Contribution to Angiogenic Processes in Tissue Regeneration.

Int J Mol Sci. 2022-2-22

[4]
Behind the Scenes of Extracellular Vesicle Therapy for Skin Injuries and Disorders.

Adv Wound Care (New Rochelle). 2022-11

[5]
Angiogenic Effects and Crosstalk of Adipose-Derived Mesenchymal Stem/Stromal Cells and Their Extracellular Vesicles with Endothelial Cells.

Int J Mol Sci. 2021-10-8

[6]
Role of Exosomes in Dermal Wound Healing: A Systematic Review.

J Invest Dermatol. 2022-3

[7]
Clinical Potential of Extracellular Vesicles in Type 2 Diabetes.

Front Endocrinol (Lausanne). 2020

[8]
Rejuvenation of mesenchymal stem cells by extracellular vesicles inhibits the elevation of reactive oxygen species.

Sci Rep. 2020-10-14

[9]
PLGF-1 contained in normal wound myofibroblast-derived microvesicles stimulated collagen production by dermal fibroblasts.

J Cell Commun Signal. 2020-12

[10]
Microvesicles from Human Immortalized Cell Lines of Endothelial Progenitor Cells and Mesenchymal Stem/Stromal Cells of Adipose Tissue Origin as Carriers of Bioactive Factors Facilitating Angiogenesis.

Stem Cells Int. 2020-6-15

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