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细胞接种加速高血压小鼠组织工程构建物的血管化。

Cell seeding accelerates the vascularization of tissue engineering constructs in hypertensive mice.

机构信息

Division of Cranio-Maxillo-Facial and Oral Surgery, University Hospital Zurich, University of Zurich, Frauenklinikstrasse 24, 8091, Zurich, Switzerland.

Department of Oral and Maxillofacial Surgery, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany.

出版信息

Hypertens Res. 2021 Jan;44(1):23-35. doi: 10.1038/s41440-020-0524-z. Epub 2020 Aug 11.

Abstract

Rapid blood vessel ingrowth into transplanted constructs represents the key requirement for successful tissue engineering. Seeding three-dimensional scaffolds with suitable cells is an approved technique for this challenge. Since a plethora of patients suffer from widespread diseases that limit the capacity of neoangiogenesis (e.g., hypertension), we investigated the incorporation of cell-seeded poly-L-lactide-co-glycolide scaffolds in hypertensive (BPH/2J, group A) and nonhypertensive (BPN/3J, group B) mice. Collagen-coated scaffolds (A1 and B1) were additionally seeded with osteoblast-like (A2 and B2) and mesenchymal stem cells (A3 and B3). After implantation into dorsal skinfold chambers, inflammation and newly formed microvessels were measured using repetitive intravital fluorescence microscopy for 2 weeks. Apart from a weak inflammatory response in all groups, significantly increased microvascular densities were found in cell-seeded scaffolds (day 14, A2: 192 ± 12 cm/cm, A3: 194 ± 10 cm/cm, B2: 249 ± 19 cm/cm, B3: 264 ± 17 cm/cm) when compared with controls (A1: 129 ± 10 cm/cm, B1: 185 ± 8 cm/cm). In this context, hypertensive mice showed reduced neoangiogenesis in comparison with nonhypertensive animals. Therefore, seeding approved scaffolds with organ-specific or pluripotent cells is a very promising technique for tissue engineering in hypertensive organisms.

摘要

快速的血管向移植构建物中的生长是组织工程成功的关键要求。将合适的细胞接种到三维支架上是应对这一挑战的一种可行方法。由于许多患者患有广泛的疾病,这些疾病限制了新生血管的形成能力(例如,高血压),我们研究了将细胞接种的聚 L-丙交酯-co-乙交酯支架纳入高血压(BPH/2J,A 组)和非高血压(BPN/3J,B 组)小鼠体内的情况。我们还在胶原涂层支架(A1 和 B1)上接种了成骨样细胞(A2 和 B2)和间充质干细胞(A3 和 B3)。在将支架植入背部皮褶室后,通过重复活体荧光显微镜测量炎症和新形成的微血管,持续 2 周。除了所有组均出现较弱的炎症反应外,在细胞接种支架中发现了明显增加的微血管密度(第 14 天,A2:192±12cm/cm,A3:194±10cm/cm,B2:249±19cm/cm,B3:264±17cm/cm),与对照组相比(A1:129±10cm/cm,B1:185±8cm/cm)。在这种情况下,与非高血压动物相比,高血压小鼠的新生血管形成减少。因此,将经过批准的支架与器官特异性或多能细胞进行接种是一种在高血压机体中进行组织工程的非常有前途的技术。

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