A Scalable and Efficient Bioprocess for Manufacturing Human Pluripotent Stem Cell-Derived Endothelial Cells

Lin, Haishuang; Du, Qian; Li, Qiang; Wang, Ou; Wang, Zhanqi; Sahu, Neety; Elowsky, Christian; Liu, Kan; Zhang, Chi; Chung, Soonkyu; Duan, Bin; Lei, Yu

doi:10.1016/j.stemcr.2018.07.001

Cited by 23 publications

(26 citation statements)

References 68 publications

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“…H9s and iPSCs had similar outcomes, according to our previous studies. 50 , 51 Our results indicated the robustness of the differentiation protocol reported by Patsch et al 4 …”

Section: Resultssupporting

confidence: 78%

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Comparative Study of Human Pluripotent Stem Cell-Derived Endothelial Cells in Hydrogel-Based Culture Systems

et al. 2021

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Human pluripotent stem cell (hPSC)-derived endothelial cells (ECs) are promising cell sources for drug discovery, tissue engineering, and studying or treating vascular diseases. However, hPSC-ECs derived from different culture methods display different phenotypes. Herein, we made a detailed comparative study of hPSC-ECs from three different culture systems (e.g., 2D, 3D PNIPAAm-PEG hydrogel, and 3D alginate hydrogel cultures) based on our previous reports. We expanded hPSCs and differentiated them into ECs in three culture systems. Both 3D hydrogel systems could mimic an in vivo physiologically relevant microenvironment to protect cells from shear force and prevent cell agglomeration, leading to a high culture efficiency and a high volumetric yield. We demonstrated that hPSC-ECs produced from both hydrogel systems had similar results as 2D-ECs. The transcriptome analysis showed that PEG-ECs and alginate-ECs displayed a functional phenotype due to their higher gene expressions in vasculature development, extracellular matrix, angiogenesis, and glycolysis, while 2D-ECs showed a proliferative phenotype due to their higher gene expressions in cell proliferation. Taken together, both PEG- and alginate-hydrogel systems will significantly advance the applications of hPSC-ECs in various biomedical fields.

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“…H9s and iPSCs had similar outcomes, according to our previous studies. 50 , 51 Our results indicated the robustness of the differentiation protocol reported by Patsch et al 4 …”

Section: Resultssupporting

confidence: 78%

“…Based on our previous studies, we have managed to expand and differentiate hPSCs in 3D-PEG hydrogel 51 and 3D-alginate hydrogel cultures. 50 In this article, we made a detailed comparative study for hPSC-ECs derived from the traditional 2D culture, 3D-PEG hydrogel culture, and 3D-alginate hydrogel culture.…”

Section: Discussionmentioning

confidence: 99%

Comparative Study of Human Pluripotent Stem Cell-Derived Endothelial Cells in Hydrogel-Based Culture Systems

et al. 2021

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“…Similarly, 3-D culture of iPSC-derived endothelial cells also showed the glycolysis-dominated metabolism compared to ones in 2-D culture [34]. Moreover, human MSCs treated with interferon gamma exert an immunosuppressive phenotype by secreting PGE2/IDO and reconfigure the metabolic phenotype to aerobic glycolysis [35].…”

Section: Resultsmentioning

confidence: 99%

Genomics Analysis of Metabolic Pathways of Human Stem Cell-Derived Microglia-Like Cells and the Integrated Cortical Spheroids

Bejoy

Yuan

Song

et al. 2019

Stem Cells International

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Brain spheroids or organoids derived from human pluripotent stem cells (hiPSCs) are still not capable of completely recapitulating in vivo human brain tissue, and one of the limitations is lack of microglia. To add built-in immune function, coculture of the dorsal forebrain spheroids with isogenic microglia-like cells (D-MG) was performed in our study. The three-dimensional D-MG spheroids were analyzed for their transcriptome and compared with isogenic microglia-like cells (MG). Cortical spheroids containing microglia-like cells displayed different metabolic programming, which may affect the associated phenotype. The expression of genes related to glycolysis and hypoxia signaling was increased in cocultured D-MG spheroids, indicating the metabolic shift to aerobic glycolysis, which is in favor of M1 polarization of microglia-like cells. In addition, the metabolic pathways and the signaling pathways involved in cell proliferation, cell death, PIK3/AKT/mTOR signaling, eukaryotic initiation factor 2 pathway, and Wnt and Notch pathways were analyzed. The results demonstrate the activation of mTOR and p53 signaling, increased expression of Notch ligands, and the repression of NF-κB and canonical Wnt pathways, as well as the lower expression of cell cycle genes in the cocultured D-MG spheroids. This analysis indicates that physiological 3-D microenvironment may reshape the immunity of in vitro cortical spheroids and better recapitulate in vivo brain tissue function for disease modeling and drug screening.

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“…It most likely through regulation of the ETS family transcription factors, ERG and FLI1 which were important to endothelial cell development [68]. Except for growth factors and small molecules, 3D culture also enhanced differentiation efficiency; the 3D thermoreversible PNIPAAm-PEG hydrogel provided 3D space for cell growth and acted as a physical barrier to prevent the cell from agglomeration and the shear force during the differentiation of endothelial cell [69]. More importantly, iPSC-or ESC-derived endothelial cells are capable of forming capillary-like structures in vitro and integrating into the host vasculature in vivo [18].…”

Section: Endothelial Cells Derived By Bioactive Moleculementioning

confidence: 99%

Bioactive Molecules for Skin Repair and Regeneration: Progress and Perspectives

Chen

Hou

Zhong

et al. 2019

Stem Cells International

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Skin regeneration is a vexing problem in the field of regenerative medicine. A bioactive molecule-based strategy has been frequently used in skin wound healing in recent years. Bioactive molecules are practical tools for regulating cellular processes and have been applied to control cellular differentiation, dedifferentiation, and reprogramming. In this review, we focus on recent progress in the use of bioactive molecules in skin regenerative medicine, by which desired cell types can be generated in vitro for cell therapy and conventional therapeutics can be developed to repair and regenerate skin in vivo through activation of the endogenous repairing potential. We further prospect that the bioactive molecule-base method might be one of the promising strategies to achieve in situ skin regeneration in the future.

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A Scalable and Efficient Bioprocess for Manufacturing Human Pluripotent Stem Cell-Derived Endothelial Cells

Cited by 23 publications

References 68 publications

Comparative Study of Human Pluripotent Stem Cell-Derived Endothelial Cells in Hydrogel-Based Culture Systems

Comparative Study of Human Pluripotent Stem Cell-Derived Endothelial Cells in Hydrogel-Based Culture Systems

Genomics Analysis of Metabolic Pathways of Human Stem Cell-Derived Microglia-Like Cells and the Integrated Cortical Spheroids

Bioactive Molecules for Skin Repair and Regeneration: Progress and Perspectives

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