Dental pulp mesenchymal stem cell (DPSCs)-derived soluble factors, produced under hypoxic conditions, support angiogenesis via endothelial cell activation and generation of M2-like macrophages.

IF 9 2区 医学 Q1 CELL BIOLOGY Journal of Biomedical Science Pub Date : 2024-11-04 DOI:10.1186/s12929-024-01087-6
Ludovica Barone, Martina Cucchiara, Maria Teresa Palano, Barbara Bassani, Matteo Gallazzi, Federica Rossi, Mario Raspanti, Piero Antonio Zecca, Gianluca De Antoni, Christina Pagiatakis, Roberto Papait, Giovanni Bernardini, Antonino Bruno, Rosalba Gornati
{"title":"Dental pulp mesenchymal stem cell (DPSCs)-derived soluble factors, produced under hypoxic conditions, support angiogenesis via endothelial cell activation and generation of M2-like macrophages.","authors":"Ludovica Barone, Martina Cucchiara, Maria Teresa Palano, Barbara Bassani, Matteo Gallazzi, Federica Rossi, Mario Raspanti, Piero Antonio Zecca, Gianluca De Antoni, Christina Pagiatakis, Roberto Papait, Giovanni Bernardini, Antonino Bruno, Rosalba Gornati","doi":"10.1186/s12929-024-01087-6","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Cell therapy has emerged as a revolutionary tool to repair damaged tissues by restoration of an adequate vasculature. Dental Pulp stem cells (DPSC), due to their easy biological access, ex vivo properties, and ability to support angiogenesis have been largely explored in regenerative medicine.</p><p><strong>Methods: </strong>Here, we tested the capability of Dental Pulp Stem Cell-Conditioned medium (DPSC-CM), produced in normoxic (DPSC-CM Normox) or hypoxic (DPSC-CM Hypox) conditions, to support angiogenesis via their soluble factors. CMs were characterized by a secretome protein array, then used for in vivo and in vitro experiments. In in vivo experiments, DPSC-CMs were associated to an Ultimatrix sponge and injected in nude mice. After excision, Ultimatrix were assayed by immunohistochemistry, electron microscopy and flow cytometry, to evaluate the presence of endothelial, stromal, and immune cells. For in vitro procedures, DPSC-CMs were used on human umbilical-vein endothelial cells (HUVECs), to test their effects on cell adhesion, migration, tube formation, and on their capability to recruit human CD14<sup>+</sup> monocytes.</p><p><strong>Results: </strong>We found that DPSC-CM Hypox exert stronger pro-angiogenic activities, compared with DPSC-CM Normox, by increasing the frequency of CD31<sup>+</sup> endothelial cells, the number of vessels and hemoglobin content in the Ultimatrix sponges. We observed that Utimatrix sponges associated with DPSC-CM Hypox or DPSC-CM Normox shared similar capability to recruit CD45<sup>-</sup> stromal cells, CD45<sup>+</sup> leukocytes, F4/80<sup>+</sup> macrophages, CD80<sup>+</sup> M1-macrophages and CD206<sup>+</sup> M2-macropages. We also observed that DPSC-CM Hypox and DPSC-CM Normox have similar capabilities to support HUVEC adhesion, migration, induction of a pro-angiogenic gene signature and the generation of capillary-like structures, together with the ability to recruit human CD14<sup>+</sup> monocytes.</p><p><strong>Conclusions: </strong>Our results provide evidence that DPSCs-CM, produced under hypoxic conditions, can be proposed as a tool able to support angiogenesis via macrophage polarization, suggesting its use to overcome the issues and restrictions associated with the use of staminal cells.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":null,"pages":null},"PeriodicalIF":9.0000,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11533415/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Biomedical Science","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12929-024-01087-6","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Background: Cell therapy has emerged as a revolutionary tool to repair damaged tissues by restoration of an adequate vasculature. Dental Pulp stem cells (DPSC), due to their easy biological access, ex vivo properties, and ability to support angiogenesis have been largely explored in regenerative medicine.

Methods: Here, we tested the capability of Dental Pulp Stem Cell-Conditioned medium (DPSC-CM), produced in normoxic (DPSC-CM Normox) or hypoxic (DPSC-CM Hypox) conditions, to support angiogenesis via their soluble factors. CMs were characterized by a secretome protein array, then used for in vivo and in vitro experiments. In in vivo experiments, DPSC-CMs were associated to an Ultimatrix sponge and injected in nude mice. After excision, Ultimatrix were assayed by immunohistochemistry, electron microscopy and flow cytometry, to evaluate the presence of endothelial, stromal, and immune cells. For in vitro procedures, DPSC-CMs were used on human umbilical-vein endothelial cells (HUVECs), to test their effects on cell adhesion, migration, tube formation, and on their capability to recruit human CD14+ monocytes.

Results: We found that DPSC-CM Hypox exert stronger pro-angiogenic activities, compared with DPSC-CM Normox, by increasing the frequency of CD31+ endothelial cells, the number of vessels and hemoglobin content in the Ultimatrix sponges. We observed that Utimatrix sponges associated with DPSC-CM Hypox or DPSC-CM Normox shared similar capability to recruit CD45- stromal cells, CD45+ leukocytes, F4/80+ macrophages, CD80+ M1-macrophages and CD206+ M2-macropages. We also observed that DPSC-CM Hypox and DPSC-CM Normox have similar capabilities to support HUVEC adhesion, migration, induction of a pro-angiogenic gene signature and the generation of capillary-like structures, together with the ability to recruit human CD14+ monocytes.

Conclusions: Our results provide evidence that DPSCs-CM, produced under hypoxic conditions, can be proposed as a tool able to support angiogenesis via macrophage polarization, suggesting its use to overcome the issues and restrictions associated with the use of staminal cells.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
牙髓间充质干细胞(DPSCs)在缺氧条件下产生的可溶性因子可通过激活内皮细胞和生成 M2 样巨噬细胞支持血管生成。
背景:细胞疗法已成为一种革命性的工具,可通过恢复充足的血管来修复受损组织。方法:在此,我们测试了牙髓干细胞条件培养基(DPSC-CM)在常氧(DPSC-CM Normox)或缺氧(DPSC-CM Hypox)条件下通过其可溶性因子支持血管生成的能力。CM通过分泌组蛋白阵列进行表征,然后用于体内和体外实验。在体内实验中,DPSC-CMs 与 Ultimatrix 海绵相连,并注射到裸鼠体内。切除后,Ultimatrix 通过免疫组化、电子显微镜和流式细胞术进行检测,以评估内皮细胞、基质细胞和免疫细胞的存在。在体外程序中,DPSC-CMs 被用于人脐静脉内皮细胞(HUVECs),以测试它们对细胞粘附、迁移、管形成的影响,以及它们招募人 CD14+ 单核细胞的能力:结果:我们发现,与 DPSC-CM Normox 相比,DPSC-CM Hypox 具有更强的促血管生成活性,能增加 Ultimatrix 海绵中 CD31+ 内皮细胞的频率、血管数量和血红蛋白含量。我们观察到,与DPSC-CM Hypox或DPSC-CM Normox相关的Utimatrix海绵具有招募CD45-基质细胞、CD45+白细胞、F4/80+巨噬细胞、CD80+ M1-巨噬细胞和CD206+ M2-巨噬细胞的相似能力。我们还观察到,DPSC-CM Hypox 和 DPSC-CM Normox 在支持 HUVEC 黏附、迁移、诱导促血管生成基因特征和生成毛细血管样结构方面具有相似的能力,同时还具有招募人类 CD14+ 单核细胞的能力:我们的研究结果证明,在缺氧条件下产生的 DPSCs-CM 可作为一种通过巨噬细胞极化支持血管生成的工具,建议使用它来克服与使用雄蕊细胞相关的问题和限制。
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 去求助
来源期刊
Journal of Biomedical Science
Journal of Biomedical Science 医学-医学:研究与实验
CiteScore
18.50
自引率
0.90%
发文量
95
审稿时长
1 months
期刊介绍: The Journal of Biomedical Science is an open access, peer-reviewed journal that focuses on fundamental and molecular aspects of basic medical sciences. It emphasizes molecular studies of biomedical problems and mechanisms. The National Science and Technology Council (NSTC), Taiwan supports the journal and covers the publication costs for accepted articles. The journal aims to provide an international platform for interdisciplinary discussions and contribute to the advancement of medicine. It benefits both readers and authors by accelerating the dissemination of research information and providing maximum access to scholarly communication. All articles published in the Journal of Biomedical Science are included in various databases such as Biological Abstracts, BIOSIS, CABI, CAS, Citebase, Current contents, DOAJ, Embase, EmBiology, and Global Health, among others.
期刊最新文献
Role of glucagon-like peptide-1 receptor agonists in Alzheimer's disease and Parkinson's disease. Dental pulp mesenchymal stem cell (DPSCs)-derived soluble factors, produced under hypoxic conditions, support angiogenesis via endothelial cell activation and generation of M2-like macrophages. Exploring paraptosis as a therapeutic approach in cancer treatment. The molecular consequences of FOXF1 missense mutations associated with alveolar capillary dysplasia with misalignment of pulmonary veins. CD81-guided heterologous EVs present heterogeneous interactions with breast cancer cells.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1