Engineered Microenvironment for Manufacturing Human Pluripotent Stem Cell-Derived Vascular Smooth Muscle Cells

Authors

• Haishuang Lin, University of Nebraska - Lincoln
• Xuefeng Qiu, Huazhong University of Science and Technology
• Qian Du, University of Nebraska - LincolnFollow
• Qiang Li, University of Nebraska - Lincoln
• Ou Wang, University of Nebraska - LincolnFollow
• Leonard Akert, University of Nebraska - LincolnFollow
• Zhanqi Wang, Beijing Anzhen of Capital Medical University
• Dirk Anderson, University of Nebraska - LincolnFollow
• Kan Liu, University of Nebraska - Lincoln
• Linxia Gu, University of Nebraska-LincolnFollow
• Chi Zhang, University of Nebraska-LincolnFollow
• Yuguo Lei, University of Nebraska-LincolnFollow

Date of this Version

2019

Document Type

Article

Citation

Stem Cell Reports | Vol. 12 | 84–97

Comments

Copyright 2018 The Author(s).

Open access

https://doi.org/10.1016/j.stemcr.2018.11.009

Abstract

Human pluripotent stem cell-derived vascular smooth muscle cells (hPSC-VSMCs) are of great value for disease modeling, drug screening, cell therapies, and tissue engineering. However, producing a high quantity of hPSC-VSMCs with current cell culture technologies remains very challenging. Here, we report a scalable method for manufacturing hPSC-VSMCs in alginate hydrogel microtubes (i.e., AlgTubes), which protect cells from hydrodynamic stresses and limit cell mass to <400 >μm ensure efficient mass transport. The tubes provide cells a friendly microenvironment, leading to extremely high culture efficiency.We have shown that hPSC-VSMCs can be generated in 10 days with high viability, high purity, and high yield (~5.0 x 10⁸ cells/mL). Phenotype and gene expression showed that VSMCs made in AlgTubes and VSMCs made in 2D cultures were similar overall. However, AlgTube-VSMCs had higher expression of genes related to vasculature development and angiogenesis, and 2D-VSMCs had higher expression of genes related to cell death and biosynthetic processes.