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Introduction: Generating new lymphatic vessels has been postulated as an innovative therapeutic strategy for various disease phenotypes, including neurodegenerative diseases, metabolic syndrome, cardiovascular disease, and lymphedema. Yet, compared to the blood vascular system, protocols to differentiate human induced pluripotent stem cells (hiPSCs) into lymphatic endothelial cells (LECs) are still lacking. Methods: Transcription factors, ETS2 and ETV2 are key regulators of embryonic vascular development, including lymphatic specification. While ETV2 has been shown to efficiently generate blood endothelial cells, little is known about ETS2 and its role in lymphatic differentiation. Here, we describe a method for rapid and efficient generation of LECs using transcription factors, ETS2 and ETV2. Results: This approach reproducibly differentiates four diverse hiPSCs into LECs with exceedingly high efficiency. Timely activation of ETS2 was critical, to enable its interaction with Prox1, a master lymphatic regulator. Differentiated LECs express key lymphatic markers, VEGFR3, LYVE-1, and Podoplanin, in comparable levels to mature LECs. The differentiated LECs are able to assemble into stable lymphatic vascular networks in vitro, and secrete key lymphangiocrine, reelin. Conclusion: Overall, our protocol has broad applications for basic study of lymphatic biology, as well as toward various approaches in lymphatic regeneration and personalized medicine.
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Synthetic hyaluronic acid coating preserves the phenotypes of lymphatic endothelial cells
Surface coating with dopamine conjugated hyaluronic acid (HA–DP) can interact with lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) to preserve the phenotypes and functionality of lymphatic endothelial cells (LECs).
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- Award ID(s):
- 2047903
- PAR ID:
- 10528108
- Publisher / Repository:
- Biomaterials Science
- Date Published:
- Journal Name:
- Biomaterials Science
- Volume:
- 11
- Issue:
- 22
- ISSN:
- 2047-4830
- Page Range / eLocation ID:
- 7346 to 7357
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/d3bm00873h
