Laschke Matthias W, Kontaxi Elena, Scheuer Claudia, Heß Alexander, Karschnia Philipp, Menger Michael D
Institute for Clinical & Experimental Surgery, Saarland University, Homburg/Saar, Germany.
J Tissue Eng. 2019 Sep 27;10:2041731419879837. doi: 10.1177/2041731419879837. eCollection 2019 Jan-Dec.
Angiogenesis in adipose tissue is promoted by insulin-like growth factor 1 signaling. We analyzed whether this regulatory mechanism also improves the angiogenic activity of adipose tissue-derived microvascular fragments. Murine adipose tissue-derived microvascular fragments were cultivated for 24 h in the University of Wisconsin (UW) solution supplemented with vehicle, insulin-like growth factor 1, or a combination of insulin-like growth factor 1 and insulin-like growth factor-binding protein 4. Subsequently, we assessed their cellular composition, viability, proliferation, and growth factor expression. Moreover, cultivated adipose tissue-derived microvascular fragments were seeded onto collagen-glycosaminoglycan scaffolds, which were implanted into dorsal skinfold chambers to study their vascularization and incorporation. Insulin-like growth factor 1 increased the viability and growth factor expression of adipose tissue-derived microvascular fragments without affecting their cellular composition and proliferation. Accordingly, scaffolds containing insulin-like growth factor 1-stimulated adipose tissue-derived microvascular fragments exhibited an enhanced in vivo vascularization and incorporation. These positive insulin-like growth factor 1 effects were reversed by additional exposure of adipose tissue-derived microvascular fragments to insulin-like growth factor-binding protein 4. Our findings indicate that insulin-like growth factor 1 stimulation of adipose tissue-derived microvascular fragments is suitable to improve their vascularization capacity.
胰岛素样生长因子1信号通路可促进脂肪组织中的血管生成。我们分析了这种调节机制是否也能改善脂肪组织来源的微血管片段的血管生成活性。将小鼠脂肪组织来源的微血管片段在补充有溶媒、胰岛素样生长因子1或胰岛素样生长因子1与胰岛素样生长因子结合蛋白4组合的威斯康星大学(UW)溶液中培养24小时。随后,我们评估了它们的细胞组成、活力、增殖和生长因子表达。此外,将培养的脂肪组织来源的微血管片段接种到胶原-糖胺聚糖支架上,然后植入背部皮褶小室中,以研究它们的血管化和整合情况。胰岛素样生长因子1增加了脂肪组织来源的微血管片段的活力和生长因子表达,而不影响其细胞组成和增殖。因此,含有胰岛素样生长因子1刺激的脂肪组织来源的微血管片段的支架在体内表现出增强的血管化和整合。脂肪组织来源的微血管片段额外暴露于胰岛素样生长因子结合蛋白4后,胰岛素样生长因子1的这些积极作用被逆转。我们的研究结果表明,胰岛素样生长因子1刺激脂肪组织来源的微血管片段适合于提高其血管化能力。