Department of Oral and Maxillofacial Surgery, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
Microvasc Res. 2013 Nov;90:71-9. doi: 10.1016/j.mvr.2013.07.006. Epub 2013 Jul 27.
Bone marrow derived mesenchymal stem cells (bmMSCs) are widely used for the generation of tissue engineering constructs, since they can differentiate into different cell types occurring in bone tissues. Until now their use for the generation of tissue engineering constructs is limited. All cells inside a tissue engineering construct die within a short period of time after implantation of the construct because vascularization and establishment of connections to the recipient circulatory system is a time consuming process. We therefore compared the influences of bmMSC, VEGF and a combination of both on the early processes of vascularization, utilizing the mice skinfold chamber model and intravital fluorescence microscopy. Tissue engineering constructs based on collagen coated Poly d,l-lactide-co-glycolide (PLGA) scaffolds, were either functionalized by coating with vascular endothelial growth factor (VEGF) or vitalized with bmMSC. PLGA without cells and growth factor was used as the control group. Functionalized and vitalized tissue engineering constructs showed an accelerated growth of microvessels compared to controls. Only marginal differences in vascular growth were detected between VEGF containing and bmMSC containing constructs. Constructs containing VEGF and bmMSC showed a further enhanced microvascular growth at day 14. We conclude that bmMSCs are well suited for bone tissue engineering applications, since they are a valuable source of angiogenic growth factors and are able to differentiate into the tissue specific cell types of interest. The dynamic process of vascularization triggered by growth factor producing cells can be amplified and stabilized with the addition of accessory growth factors, leading to a persisting angiogenesis, but strategies are needed that enhance the resistance of bmMSC to hypoxia and increase survival of these cells until the tissue engineering construct has build up a functional vascular system.
骨髓间充质干细胞(bmMSCs)广泛用于组织工程构建,因为它们可以分化为骨组织中出现的不同细胞类型。到目前为止,它们在组织工程构建中的应用受到限制。由于血管生成和与受体循环系统建立连接是一个耗时的过程,因此植入构建体后,构建体内部的所有细胞都会在短时间内死亡。因此,我们利用小鼠皮肤袋模型和活体荧光显微镜比较了 bmMSC、VEGF 及其组合对血管生成早期过程的影响。基于胶原涂覆的聚 d,l-乳酸-co-乙醇酸(PLGA)支架的组织工程构建体通过涂覆血管内皮生长因子(VEGF)或与 bmMSC 共培养来功能化。不含有细胞和生长因子的 PLGA 用作对照组。功能化和活化的组织工程构建体与对照组相比,显示出微血管生长的加速。在含有 VEGF 和 bmMSC 的构建体之间仅检测到血管生长的微小差异。含有 VEGF 和 bmMSC 的构建体在第 14 天显示出进一步增强的微血管生长。我们得出结论,bmMSC 非常适合骨组织工程应用,因为它们是血管生成生长因子的有价值来源,并且能够分化为感兴趣的组织特异性细胞类型。通过添加辅助生长因子,可以放大和稳定由产生生长因子的细胞触发的血管生成动态过程,从而导致持续的血管生成,但需要增强 bmMSC 对缺氧的抵抗力并增加这些细胞的存活率,直到组织工程构建体建立起功能性血管系统。