Hall Meghan E, Mohtaram Nima Khadem, Willerth Stephanie M, Edwards Roderick
Department of Mathematics and Statistics, University of Victoria, Victoria, Canada.
Department of Mechanical Engineering, University of Victoria, Victoria, Canada.
J Biol Eng. 2017 Oct 23;11:38. doi: 10.1186/s13036-017-0080-5. eCollection 2017.
Human induced pluripotent stem cells (hiPSCs) can form any tissue found in the body, making them attractive for regenerative medicine applications. Seeding hiPSC aggregates into biomaterial scaffolds can control their differentiation into specific tissue types. Here we develop and analyze a mathematical model of hiPSC aggregate behavior when seeded on melt electrospun scaffolds with defined topography.
We used ordinary differential equations to model the different cellular populations (stem, progenitor, differentiated) present in our scaffolds based on experimental results and published literature. Our model successfully captures qualitative features of the cellular dynamics observed experimentally. We determined the optimal parameter sets to maximize specific cellular populations experimentally, showing that a physiologic oxygen level (∼ 5%) increases the number of neural progenitors and differentiated neurons compared to atmospheric oxygen levels (∼ 21%) and a scaffold porosity of ∼ 63% maximizes aggregate size.
Our mathematical model determined the key factors controlling hiPSC behavior on melt electrospun scaffolds, enabling optimization of experimental parameters.
人类诱导多能干细胞（hiPSC）可以形成体内发现的任何组织，这使得它们在再生医学应用中具有吸引力。将hiPSC聚集体接种到生物材料支架中可以控制它们分化为特定的组织类型。在此，我们建立并分析了hiPSC聚集体接种在具有特定形貌的熔体静电纺丝支架上时的数学模型。
我们基于实验结果和已发表的文献，使用常微分方程对支架中存在的不同细胞群体（干细胞、祖细胞、分化细胞）进行建模。我们的模型成功捕捉到了实验观察到的细胞动力学的定性特征。我们通过实验确定了使特定细胞群体最大化的最佳参数集，结果表明，与大气氧水平（约21%）相比，生理氧水平（约5%）可增加神经祖细胞和分化神经元的数量，约63%的支架孔隙率可使聚集体尺寸最大化。
我们的数学模型确定了控制hiPSC在熔体静电纺丝支架上行为的关键因素，从而能够优化实验参数。
