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

Haishuang Lin; Xuefeng Qiu; Qian Du; Qiang Li; Ou Wang; Leonard Akert; Zhanqi Wang; Dirk Anderson; Kan Liu; Linxia Gu; Chi Zhang; Yuguo Lei

Stem Cell Reports (Jan 2019)

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

Haishuang Lin,
Xuefeng Qiu,
Qian Du,
Qiang Li,
Ou Wang,
Leonard Akert,
Zhanqi Wang,
Dirk Anderson,
Kan Liu,
Linxia Gu,
Chi Zhang,
Yuguo Lei

Affiliations

Haishuang Lin: Department of Chemical and Biomolecular Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588, USA
Xuefeng Qiu: Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
Qian Du: Department of Biological Systems Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588, USA
Qiang Li: Department of Chemical and Biomolecular Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588, USA; Biomedical Engineering Program, University of Nebraska-Lincoln, Lincoln, NE 68588, USA
Ou Wang: Department of Chemical and Biomolecular Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588, USA; Biomedical Engineering Program, University of Nebraska-Lincoln, Lincoln, NE 68588, USA
Leonard Akert: Department of Chemical and Biomolecular Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588, USA
Zhanqi Wang: Department of Vascular Surgery, Beijing Anzhen Hospital of Capital Medical University, Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing 100029, China
Dirk Anderson: Center for Biotechnology, University of Nebraska-Lincoln, Lincoln, NE 68588, USA
Kan Liu: Department of Biological Systems Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588, USA
Linxia Gu: Department of Mechanical and Materials Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588, USA
Chi Zhang: Department of Biological Systems Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588, USA
Yuguo Lei: Department of Chemical and Biomolecular Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588, USA; Biomedical Engineering Program, University of Nebraska-Lincoln, Lincoln, NE 68588, USA; Mary and Dick Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, NE 68198, USA; Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA; Corresponding author

Journal volume & issue: Vol. 12, no. 1
pp. 84 – 97

Abstract

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Summary: 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 to 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 × 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. : Human pluripotent stem cell-derived vascular smooth muscle cells (hPSC-VSMCs) are of great value for regenerative medicine. In this article, Lei and colleagues describe a method to manufacture hPSC-VSMCs in alginate hydrogel microtubes, which provide cells a cell-friendly microenvironment, leading to extremely high culture efficiency. The method is scalable and has potential to make hPSC-VSMCs broadly accessible. Keywords: human pluripotent stem cells, alginate hydrogel tube, 3D culture, vascular smooth muscle cells

Published in Stem Cell Reports

ISSN: 2213-6711 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General); Science: Biology (General)
Website: http://www.cell.com/stem-cell-reports/home

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