TY - JOUR
T1 - Three-Dimensional In Vitro Lymphangiogenesis Model in Tumor Microenvironment
AU - Cho, Youngkyu
AU - Na, Kyuhwan
AU - Jun, Yesl
AU - Won, Jihee
AU - Yang, Ji Hun
AU - Chung, Seok
N1 - Funding Information:
This work was supported by Samsung Research Funding and Incubation Center of Samsung Electronics under Project number SRFC-IT1901-10.
Publisher Copyright:
© Copyright © 2021 Cho, Na, Jun, Won, Yang and Chung.
PY - 2021/10/4
Y1 - 2021/10/4
N2 - Lymphangiogenesis is a stage of new lymphatic vessel formation in development and pathology, such as inflammation and tumor metastasis. Physiologically relevant models of lymphatic vessels have been in demand because studies on lymphatic vessels are required for understanding the mechanism of tumor metastasis. In this study, a new three-dimensional lymphangiogenesis model in a tumor microenvironment is proposed, using a newly designed macrofluidic platform. It is verified that controllable biochemical and biomechanical cues, which contribute to lymphangiogenesis, can be applied in this platform. In particular, this model demonstrates that a reconstituted lymphatic vessel has an in vivo–like lymphatic vessel in both physical and biochemical aspects. Since biomechanical stress with a biochemical factor influences robust directional lymphatic sprouting, whether our model closely approximates in vivo, the initial lymphatics in terms of the morphological and genetic signatures is investigated. Furthermore, attempting an incorporation with a tumor spheroid, this study successfully develops a complex tumor microenvironment model for use in lymphangiogenesis and reveals the microenvironment factors that contribute to tumor metastasis. As a first attempt at a coculture model, this reconstituted model is a novel system with a fully three-dimensional structure and can be a powerful tool for pathological drug screening or disease model.
AB - Lymphangiogenesis is a stage of new lymphatic vessel formation in development and pathology, such as inflammation and tumor metastasis. Physiologically relevant models of lymphatic vessels have been in demand because studies on lymphatic vessels are required for understanding the mechanism of tumor metastasis. In this study, a new three-dimensional lymphangiogenesis model in a tumor microenvironment is proposed, using a newly designed macrofluidic platform. It is verified that controllable biochemical and biomechanical cues, which contribute to lymphangiogenesis, can be applied in this platform. In particular, this model demonstrates that a reconstituted lymphatic vessel has an in vivo–like lymphatic vessel in both physical and biochemical aspects. Since biomechanical stress with a biochemical factor influences robust directional lymphatic sprouting, whether our model closely approximates in vivo, the initial lymphatics in terms of the morphological and genetic signatures is investigated. Furthermore, attempting an incorporation with a tumor spheroid, this study successfully develops a complex tumor microenvironment model for use in lymphangiogenesis and reveals the microenvironment factors that contribute to tumor metastasis. As a first attempt at a coculture model, this reconstituted model is a novel system with a fully three-dimensional structure and can be a powerful tool for pathological drug screening or disease model.
KW - interstitial flow
KW - lymphangiogenesis
KW - lymphatic vessel
KW - organ-on-a-chip
KW - tumor microenvironment
UR - http://www.scopus.com/inward/record.url?scp=85117255081&partnerID=8YFLogxK
U2 - 10.3389/fbioe.2021.697657
DO - 10.3389/fbioe.2021.697657
M3 - Article
AN - SCOPUS:85117255081
SN - 2296-4185
VL - 9
JO - Frontiers in Bioengineering and Biotechnology
JF - Frontiers in Bioengineering and Biotechnology
M1 - 697657
ER -