Physiologically—Modeled Dynamic Stimulation and Growth Factors Induce Differentiation of Mesenchymal Stem Cells to a Vascular Endothelial Cell Phenotype

IF 1.9 4区医学 Q3 HEMATOLOGY

Microcirculation Pub Date : 2025-03-22 DOI:10.1111/micc.70007

Mediha Gurel, Helena Zomer, Calum McFetridge, Walter L. Murfee, Peter S. McFetridge

{"title":"Physiologically—Modeled Dynamic Stimulation and Growth Factors Induce Differentiation of Mesenchymal Stem Cells to a Vascular Endothelial Cell Phenotype","authors":"Mediha Gurel, Helena Zomer, Calum McFetridge, Walter L. Murfee, Peter S. McFetridge","doi":"10.1111/micc.70007","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Objective</h3>\n \n <p>Mesenchymal stem cells (MSCs) represent an attractive option as an endothelial cell (EC) source for regenerative medicine therapies. However, the differentiation of MSCs toward an ECs phenotype can be regulated by a complex and dynamic microenvironment, including specific growth factors as well as local mechanical cues. The objective of this work was to evaluate whether Physiologically-modeled dynamic stimulation (PMDS) characterized by continuous variability in pulse frequencies mimicking the dynamic temporal range of cardiac function would enhance MSC differentiation toward ECs compared to a constant frequency stimulation.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Mesenchymal stem cells were grown in a complex growth factor cocktail versus standard culture media to initiate the endothelial differentiation process, then subsequently exposed to PMDS that vary in duration and constant flow (CF) at a fixed 10 dynes/cm<sup>2</sup> shear stress and 1.3 Hz frequency.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Both PMDS and media type strongly influence cell differentiation and function. Cells were shown to significantly upregulate eNOS activity and displayed lower TNF-a induced leukocyte adhesion compared to cells cultured under CF, consistent with a more quiescent ECs phenotype that regulates anti-inflammatory and anti-thrombotic states.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>These findings suggest that the dynamic microenvironment created by perfusion, in contrast to constant frequency, combined with growth factors, enhances MSCs differentiation toward a vascular endothelial-like phenotype.</p>\n </section>\n </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"32 3","pages":""},"PeriodicalIF":1.9000,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Microcirculation","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/micc.70007","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"HEMATOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Objective

Mesenchymal stem cells (MSCs) represent an attractive option as an endothelial cell (EC) source for regenerative medicine therapies. However, the differentiation of MSCs toward an ECs phenotype can be regulated by a complex and dynamic microenvironment, including specific growth factors as well as local mechanical cues. The objective of this work was to evaluate whether Physiologically-modeled dynamic stimulation (PMDS) characterized by continuous variability in pulse frequencies mimicking the dynamic temporal range of cardiac function would enhance MSC differentiation toward ECs compared to a constant frequency stimulation.

Methods

Mesenchymal stem cells were grown in a complex growth factor cocktail versus standard culture media to initiate the endothelial differentiation process, then subsequently exposed to PMDS that vary in duration and constant flow (CF) at a fixed 10 dynes/cm² shear stress and 1.3 Hz frequency.

Results

Both PMDS and media type strongly influence cell differentiation and function. Cells were shown to significantly upregulate eNOS activity and displayed lower TNF-a induced leukocyte adhesion compared to cells cultured under CF, consistent with a more quiescent ECs phenotype that regulates anti-inflammatory and anti-thrombotic states.

Conclusion

These findings suggest that the dynamic microenvironment created by perfusion, in contrast to constant frequency, combined with growth factors, enhances MSCs differentiation toward a vascular endothelial-like phenotype.

查看原文本刊更多论文

生理模型动态刺激和生长因子诱导间充质干细胞向血管内皮细胞表型分化

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Microcirculation 医学-外周血管病

CiteScore

5.00

自引率

4.20%

发文量

审稿时长

6-12 weeks

期刊介绍： The journal features original contributions that are the result of investigations contributing significant new information relating to the vascular and lymphatic microcirculation addressed at the intact animal, organ, cellular, or molecular level. Papers describe applications of the methods of physiology, biophysics, bioengineering, genetics, cell biology, biochemistry, and molecular biology to problems in microcirculation. Microcirculation also publishes state-of-the-art reviews that address frontier areas or new advances in technology in the fields of microcirculatory disease and function. Specific areas of interest include: Angiogenesis, growth and remodeling; Transport and exchange of gasses and solutes; Rheology and biorheology; Endothelial cell biology and metabolism; Interactions between endothelium, smooth muscle, parenchymal cells, leukocytes and platelets; Regulation of vasomotor tone; and Microvascular structures, imaging and morphometry. Papers also describe innovations in experimental techniques and instrumentation for studying all aspects of microcirculatory structure and function.