Barone Ludovica, Gallazzi Matteo, Rossi Federica, Papait Roberto, Raspanti Mario, Zecca Piero Antonio, Buonarrivo Luca, Bassani Barbara, Bernardini Giovanni, Bruno Antonino, Gornati Rosalba
Department of Biotechnology and Life Sciences, University of Insubria, 21100 Varese, Italy.
Laboratory of Innate Immunity, Unit of Molecular Pathology, Biochemistry, and Immunology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) MultiMedica, 20138 Milan, Italy.
Nanomaterials (Basel). 2023 Sep 2;13(17):2479. doi: 10.3390/nano13172479.
Among all strategies directed at developing new tools to support re-vascularization of damaged tissues, the use of pro-angiogenic soluble factors, derived from mesenchymal stem cells (MSCs), appears a promising approach for regenerative medicine. Here, we compared the feasibility of two devices, generated by coupling soluble factors of human dental pulp mesenchymal stem cells (DPSCs), with a nanostructured scaffold, to support angiogenesis once transplanted in mice. DPSCs were obtained from impacted wisdom tooth removal, usually considered surgical waste material. After 28 days, we verified the presence of active blood vessels inside the scaffold through optical and scansion electron microscopy. The mRNA expression of surface antigens related to macrophage polarization (CD68, CD80, CD86, CD163, CD206), as well as pro-angiogenic markers (CD31, CD34, CD105, Angpt1, Angpt2, CDH5) was evaluated by real-time PCR. Our results demonstrate the capability of DPSC-scaffold and DPSC soluble factors-scaffold to support angiogenesis, similarly to adipose stem cells, whereas the absence of blood vessels was found in the scaffold grafted alone. Our results provide evidence that DPSC-conditioned medium can be proposed as a cell-free preparation able to support angiogenesis, thus, providing a relevant tool to overcome the issues and restrictions associated with the use of cells.
在所有旨在开发支持受损组织再血管化新工具的策略中,使用源自间充质干细胞(MSC)的促血管生成可溶性因子,似乎是再生医学中一种很有前景的方法。在此,我们比较了两种装置的可行性,这两种装置是通过将人牙髓间充质干细胞(DPSC)的可溶性因子与纳米结构支架相结合而产生的,用于在移植到小鼠体内后支持血管生成。DPSC取自阻生智齿拔除术,通常被视为手术废料。28天后,我们通过光学显微镜和扫描电子显微镜验证了支架内活性血管的存在。通过实时PCR评估与巨噬细胞极化相关的表面抗原(CD68、CD80、CD86、CD163、CD206)以及促血管生成标志物(CD31、CD34、CD105、Angpt1、Angpt2、CDH5)的mRNA表达。我们的结果表明,DPSC-支架和DPSC可溶性因子-支架与脂肪干细胞类似,具有支持血管生成的能力,而单独移植的支架中未发现血管。我们的结果提供了证据,表明DPSC条件培养基可作为一种无细胞制剂来支持血管生成,从而提供一种相关工具来克服与细胞使用相关的问题和限制。