Peripheral sensory neurons promote angiogenesis in neurovascular models derived from hESCs
In the adult tissues, blood vessels traverse the body with neurons side by side; and share common signaling molecules. Developmental studies on animal models have shown that peripheral sensory neurons (PSNs) secrete angiogenic factors and endothelial cells (ECs) secrete neurotrophic factors which co...
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doaj-31b697ef537e4dd8add12ec0ba49c4c62021-03-25T04:27:43ZengElsevierStem Cell Research1873-50612021-04-0152102231Peripheral sensory neurons promote angiogenesis in neurovascular models derived from hESCsSathya Kannan0Marcus Lee1Senthilkumar Muthusamy2Agata Blasiak3Gopu Sriram4Tong Cao5Faculty of Dentistry, National University of Singapore, SingaporeFaculty of Dentistry, National University of Singapore, SingaporeFaculty of Dentistry, National University of Singapore, SingaporeThe N.1 Institute for Health, National University of Singapore, SingaporeFaculty of Dentistry, National University of Singapore, Singapore; NUS Centre for Additive Manufacturing (AM.NUS), National University of Singapore, Singapore; Corresponding authors at: Faculty of Dentistry, National University of Singapore, National University Centre for Oral Health Singapore, 9 Lower Kent Ridge Road, 119085, Singapore.Faculty of Dentistry, National University of Singapore, Singapore; Corresponding authors at: Faculty of Dentistry, National University of Singapore, National University Centre for Oral Health Singapore, 9 Lower Kent Ridge Road, 119085, Singapore.In the adult tissues, blood vessels traverse the body with neurons side by side; and share common signaling molecules. Developmental studies on animal models have shown that peripheral sensory neurons (PSNs) secrete angiogenic factors and endothelial cells (ECs) secrete neurotrophic factors which contribute to their coexistence, thereby forming the peripheral neurovascular (PNV) unit. Despite the large number of studies showing that innervation and vascularization complement each other, the interaction between human PSNs and ECs is still largely unknown. To study this interaction and to evaluate if PSNs affect angiogenesis, we derived both PSNs and ECs from human embryonic stem cells (hESCs) and developed a co-culture system. Seeding the two cell types together showed that PSNs induced endothelial morphogenesis with formation of vessel-like structures (VLSs). The PSN precursors, neural crest stem cells also induced VLS formation in the co-culture system; however, to a lesser extent. This sheds new light on the in vitro angiogenic potential of these cell types. PSNs derived from hESCs are powerful tools for studying development and disease as human PSNs are inaccessible for in vitro assays. Our novel approach, with optimized media condition allowed for integrating hESC-derived PSNs with hESC-derived ECs in three-dimensional (3D) collagen gel for creating a completely humanised PNV model. This preliminary model showed that innervation improves the development of vascularized channels in vitro, and provides insight to the development of innervated 3D models in future.http://www.sciencedirect.com/science/article/pii/S1873506121000775Human embryonic stem cellsSensory neuronsEndothelial cellsNeurovascular unitInnervationAngiogenesis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sathya Kannan Marcus Lee Senthilkumar Muthusamy Agata Blasiak Gopu Sriram Tong Cao |
spellingShingle |
Sathya Kannan Marcus Lee Senthilkumar Muthusamy Agata Blasiak Gopu Sriram Tong Cao Peripheral sensory neurons promote angiogenesis in neurovascular models derived from hESCs Stem Cell Research Human embryonic stem cells Sensory neurons Endothelial cells Neurovascular unit Innervation Angiogenesis |
author_facet |
Sathya Kannan Marcus Lee Senthilkumar Muthusamy Agata Blasiak Gopu Sriram Tong Cao |
author_sort |
Sathya Kannan |
title |
Peripheral sensory neurons promote angiogenesis in neurovascular models derived from hESCs |
title_short |
Peripheral sensory neurons promote angiogenesis in neurovascular models derived from hESCs |
title_full |
Peripheral sensory neurons promote angiogenesis in neurovascular models derived from hESCs |
title_fullStr |
Peripheral sensory neurons promote angiogenesis in neurovascular models derived from hESCs |
title_full_unstemmed |
Peripheral sensory neurons promote angiogenesis in neurovascular models derived from hESCs |
title_sort |
peripheral sensory neurons promote angiogenesis in neurovascular models derived from hescs |
publisher |
Elsevier |
series |
Stem Cell Research |
issn |
1873-5061 |
publishDate |
2021-04-01 |
description |
In the adult tissues, blood vessels traverse the body with neurons side by side; and share common signaling molecules. Developmental studies on animal models have shown that peripheral sensory neurons (PSNs) secrete angiogenic factors and endothelial cells (ECs) secrete neurotrophic factors which contribute to their coexistence, thereby forming the peripheral neurovascular (PNV) unit. Despite the large number of studies showing that innervation and vascularization complement each other, the interaction between human PSNs and ECs is still largely unknown. To study this interaction and to evaluate if PSNs affect angiogenesis, we derived both PSNs and ECs from human embryonic stem cells (hESCs) and developed a co-culture system. Seeding the two cell types together showed that PSNs induced endothelial morphogenesis with formation of vessel-like structures (VLSs). The PSN precursors, neural crest stem cells also induced VLS formation in the co-culture system; however, to a lesser extent. This sheds new light on the in vitro angiogenic potential of these cell types. PSNs derived from hESCs are powerful tools for studying development and disease as human PSNs are inaccessible for in vitro assays. Our novel approach, with optimized media condition allowed for integrating hESC-derived PSNs with hESC-derived ECs in three-dimensional (3D) collagen gel for creating a completely humanised PNV model. This preliminary model showed that innervation improves the development of vascularized channels in vitro, and provides insight to the development of innervated 3D models in future. |
topic |
Human embryonic stem cells Sensory neurons Endothelial cells Neurovascular unit Innervation Angiogenesis |
url |
http://www.sciencedirect.com/science/article/pii/S1873506121000775 |
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