MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, Netherlands.
Tissue Eng Part A. 2021 Aug;27(15-16):1055-1063. doi: 10.1089/ten.TEA.2020.0080. Epub 2020 Nov 17.
Vascularization is undoubtedly one of the greatest challenges in tissue engineering. Its importance is particularly evident when considering the transplantation of (bioengineered) pancreatic islets of Langerhans, which are highly sensitive to the delivery of oxygen and nutrients for their survival and function. Here we studied pseudoislets of Langerhans, which are three-dimensional spheroids composed of β (INS1E), α (alpha TC-1), and endothelial (HUVEC) cells, and were interested in how the location and prevalence of the different cell types affected the presence of endothelial cells in the pseudoislet. We hypothesized that alpha (α) cells play an essential role in islet self-assembly and the incorporation of endothelial cells into the pseudoislet, and are thus important to consider in tissue engineering or regenerative medicine strategies, which typically focuses on the insulin-producing beta (β) cells alone. We first determined the effect of changing the relative ratios of the cells and found the cell distribution converged on a steady state of ∼21% α cells, 74% β cells, and 5% endothelial cells after 10 days of culture regardless of their respective ratios at seeding. We also found that the incorporation of endothelial cells was related to the pseudoislet size, with more endothelial cells found in the core of larger pseudoislets following a concomitant increase of α cells and a decrease in β cells. Finally, we observed that both endothelial and β cells were found adjacent to α cells significantly more frequently than to each other. In conclusion, this study demonstrates that the self-assembly of a pseudoislet is an intrinsically cell-regulated process. The endothelial cells had preferential proximity to the α cells, and this persisted even when challenged with changing the cell ratios and numbers. This study gives insight into the rules governing the self-organization of pseudoislets and suggests an important role for α cells to promote the incorporation of endothelial cells.
血管生成无疑是组织工程学面临的最大挑战之一。在考虑胰岛细胞（生物工程）移植时，这一点尤为明显，因为胰岛细胞对氧气和营养物质的输送非常敏感，这是其生存和功能所必需的。在这里，我们研究了胰岛假聚集体，它们是由β（INS1E）、α（alpha TC-1）和内皮（HUVEC）细胞组成的三维球体，我们感兴趣的是不同细胞类型的位置和流行程度如何影响内皮细胞在假聚集体中的存在。我们假设α细胞在胰岛的自我组装和内皮细胞掺入假聚集体中发挥着重要作用，因此在组织工程或再生医学策略中需要考虑到这一点，这些策略通常仅关注产生胰岛素的β细胞。我们首先确定了改变细胞相对比例的影响，发现无论在接种时的各自比例如何，经过 10 天的培养后，细胞分布都会收敛到一个稳定状态，即约 21%的α细胞、74%的β细胞和 5%的内皮细胞。我们还发现，内皮细胞的掺入与假聚集体的大小有关，在较大的假聚集体的核心中发现了更多的内皮细胞，同时α细胞增加，β细胞减少。最后，我们观察到内皮细胞和β细胞与α细胞相邻的频率明显高于彼此相邻的频率。总之，这项研究表明，假聚集体的自我组装是一个内在的细胞调节过程。内皮细胞与α细胞具有优先的接近性，即使在改变细胞比例和数量的情况下，这种情况仍然存在。这项研究深入了解了控制假聚集体自组织的规则，并表明α细胞在促进内皮细胞掺入方面发挥着重要作用。
