Department of Plastic and Hand Surgery, University of Freiburg Medical Center, D-79106 Freiburg, Germany.
J Orthop Res. 2012 Oct;30(10):1682-9. doi: 10.1002/jor.22130. Epub 2012 Apr 16.
Angiogenesis is a fundamental process in bone formation, remodeling, and regeneration. Moreover, for the regeneration of bone in tissue engineering applications, it is essential to support neovascularization. This can be achieved by cell-based therapies using primary endothelial cells, which are able to form functional blood vessels upon implantation. In bone composite grafts, coimplanted endothelial cells do not only support neovascularization but also support osteogenic differentiation of osteoblasts and osteoprogenitor cells. In this study, we investigated the effect of endothelial cells on proliferation and cell survival of human primary osteoblasts (hOBs) and human mesenchymal stem cells (MSCs). Human umbilical vein endothelial cells (HUVECs) stimulated hOB and MSC proliferation, whereas proliferation of HUVECs was unaffected by cocultured hOBs or MSCs. The effect of HUVEC cocultivation on hOB and MSC proliferation was more pronounced in direct cocultures than in indirect cocultures, indicating that this effect is at least partially dependent on the formation of heterotypic cell contacts between HUVECs and hOBs or MSCs. Furthermore, HUVEC cocultivation reduced low-serum induced apotosis of hOBs and MSCs by a mechanism involving increased phosphorylation and inactivation of the proapoptotic protein Bad. In summary, our experiments have shown that cocultured HUVECs increase the proliferation and reduce low-serum induced apoptosis of hOBs and MSCs.
血管生成是骨形成、重塑和再生的基本过程。此外，对于组织工程应用中的骨再生，支持新血管生成至关重要。这可以通过使用原代内皮细胞的基于细胞的疗法来实现，这些细胞在植入后能够形成功能性血管。在骨复合移植物中，共植入的内皮细胞不仅支持新血管生成，还支持成骨细胞和骨祖细胞的成骨分化。在这项研究中，我们研究了内皮细胞对人原代成骨细胞（hOB）和人间充质干细胞（MSCs）增殖和细胞存活的影响。人脐静脉内皮细胞（HUVEC）刺激 hOB 和 MSC 增殖，而 HUVEC 增殖不受共培养的 hOB 或 MSC 的影响。HUVEC 共培养对 hOB 和 MSC 增殖的影响在直接共培养中比间接共培养更为明显，表明这种效应至少部分依赖于 HUVEC 与 hOB 或 MSC 之间形成异型细胞接触。此外，HUVEC 共培养通过增加促凋亡蛋白 Bad 的磷酸化和失活来减少低血清诱导的 hOB 和 MSC 凋亡。总之，我们的实验表明，共培养的 HUVEC 增加了 hOB 和 MSC 的增殖，并减少了低血清诱导的凋亡。
