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Biophysical quantification of reorganization dynamics of human pancreatic islets during co-culture with adipose-derived stem cells
Analyst ( IF 3.6 ) Pub Date : 2022-05-11 , DOI: 10.1039/d2an00222a Karina Torres-Castro 1 , Mohammad S Azimi 2 , Walter B Varhue 1 , Carlos Honrado 1 , Shayn M Peirce 2 , Nathan S Swami 1
Analyst ( IF 3.6 ) Pub Date : 2022-05-11 , DOI: 10.1039/d2an00222a Karina Torres-Castro 1 , Mohammad S Azimi 2 , Walter B Varhue 1 , Carlos Honrado 1 , Shayn M Peirce 2 , Nathan S Swami 1
Affiliation
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Islet transplantation is a potential therapy for type 1 diabetes, but it is expensive due to limited pancreas donor numbers and the variability in islet quality. The latter is often addressed by co-culture of harvested islets with stem cells to promote in vitro remodeling of their basement membrane and enable expression of angiogenic factors for enhancing vascularization. However, given the heterogeneity in islet size, shape and function, there is a need for metrics to assess the reorganization dynamics of single islets over the co-culture period. Based on shape-evolution of individual multi-cell aggregates formed during co-culture of human islets with adipose derived stem cells and the pressures required for their bypass through microfluidic constrictions, we present size-normalized biomechanical metrics for monitoring the reorganization. Aggregates below a threshold size exhibit faster reorganization, as evident from rise in their biomechanical opacity and tightening of their size distribution, but this size threshold increases over culture time to include a greater proportion of the aggregates. Such biomechanical metrics can quantify the subpopulation of reorganized aggregates by distinguishing them versus those with incomplete reorganization, over various timepoints during the co-culture.
中文翻译：
与脂肪干细胞共培养过程中人胰岛重组动力学的生物物理量化
胰岛移植是 1 型糖尿病的一种潜在疗法，但由于胰腺供体数量有限和胰岛质量的可变性，它的成本很高。后者通常通过将收获的胰岛与干细胞共培养来促进体外培养来解决重塑它们的基底膜并使血管生成因子能够表达以增强血管形成。然而，鉴于胰岛大小、形状和功能的异质性，需要有指标来评估单个胰岛在共培养期间的重组动态。基于在人类胰岛与脂肪衍生干细胞共培养过程中形成的单个多细胞聚集体的形状演变以及通过微流体收缩绕过它们所需的压力，我们提出了用于监测重组的尺寸标准化生物力学指标。低于阈值大小的聚集体表现出更快的重组，这从它们的生物力学不透明度的上升和它们的尺寸分布的收紧中可以看出，但是这个尺寸阈值随着培养时间的增加而增加，以包括更大比例的聚集体。与那些重组不完全的人相比，在共培养期间的不同时间点。
更新日期：2022-05-11
中文翻译：
与脂肪干细胞共培养过程中人胰岛重组动力学的生物物理量化
胰岛移植是 1 型糖尿病的一种潜在疗法，但由于胰腺供体数量有限和胰岛质量的可变性，它的成本很高。后者通常通过将收获的胰岛与干细胞共培养来促进体外培养来解决重塑它们的基底膜并使血管生成因子能够表达以增强血管形成。然而，鉴于胰岛大小、形状和功能的异质性，需要有指标来评估单个胰岛在共培养期间的重组动态。基于在人类胰岛与脂肪衍生干细胞共培养过程中形成的单个多细胞聚集体的形状演变以及通过微流体收缩绕过它们所需的压力，我们提出了用于监测重组的尺寸标准化生物力学指标。低于阈值大小的聚集体表现出更快的重组，这从它们的生物力学不透明度的上升和它们的尺寸分布的收紧中可以看出，但是这个尺寸阈值随着培养时间的增加而增加，以包括更大比例的聚集体。与那些重组不完全的人相比，在共培养期间的不同时间点。
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