Objective: We compared the capability of human umbilical vein endothelial cells (HUVECs), induced pluripotent stem cell (iPSC)-derived endothelial cells (iECs), and human dermal blood endothelial cells (HDBECs) to effectively vascularize engineered human skin constructs (HSCs) in vitro and on immunodeficient mice. Approach: We quantified the angiogenesis within HSCs both in vitro and in vivo through computational analyses of immunofluorescent (IF) staining. We assayed with real-time quantitative PCR (RT-qPCR) the expression of key endothelial, dermal, and epidermal genes in 2D culture and HSCs. Epidermal integrity and proliferation were also evaluated through haematoxylin and eosin staining, and IF staining. Results: IF confirmed iEC commitment to endothelial phenotype. RT-qPCR showed HUVECs and iECs immaturity compared with HDBECs. In vitro, the vascular network extension was comparable for HDBECs and HUVECs despite differences in vascular diameter, whereas iECs formed unorganized rudimentary tubular structures. In vivo, all ECs produced discrete vascular networks of varying dimensions. HUVECs and HDBECs maintained a higher proliferation of basal keratinocytes. HDBECs had the best impact on extracellular matrix expression, and epidermal proliferation and differentiation. Innovation: To our knowledge, this study represents the first direct and quantitative comparison of HDBECs, HUVECs, and iECs angiogenic performance in HSCs. Conclusions: Our data indicate that HUVECs and iECs can be an alternative cell source to HDBEC to promote the short-term viability of prevascularized engineered grafts. Nevertheless, HDBECs maintain their capillary identity and outperform other EC types in promoting the maturation of the dermis and epidermis. These intrinsic characteristics of HDBECs may influence the long-term function of skin grafts.
Objective: We compared the capability of human umbilical vein endothelial cells (HUVECs), induced pluripotent stem cell (iPSC)-derived endothelial cells (iECs), and human dermal blood endothelial cells (HDBECs) to effectively vascularize engineered human skin constructs (HSCs) in vitro and on immunodeficient mice. Approach: We quantified the angiogenesis within HSCs both in vitro and in vivo through computational analyses of immunofluorescent (IF) staining. We assayed with real-time quantitative PCR (RT-qPCR) the expression of key endothelial, dermal, and epidermal genes in 2D culture and HSCs. Epidermal integrity and proliferation were also evaluated through haematoxylin and eosin staining, and IF staining. Results: IF confirmed iEC commitment to endothelial phenotype. RT-qPCR showed HUVECs and iECs immaturity compared with HDBECs. In vitro, the vascular network extension was comparable for HDBECs and HUVECs despite differences in vascular diameter, whereas iECs formed unorganized rudimentary tubular structures. In vivo, all ECs produced discrete vascular networks of varying dimensions. HUVECs and HDBECs maintained a higher proliferation of basal keratinocytes. HDBECs had the best impact on extracellular matrix expression, and epidermal proliferation and differentiation. Innovation: To our knowledge, this study represents the first direct and quantitative comparison of HDBECs, HUVECs, and iECs angiogenic performance in HSCs. Conclusions: Our data indicate that HUVECs and iECs can be an alternative cell source to HDBEC to promote the short-term viability of prevascularized engineered grafts. Nevertheless, HDBECs maintain their capillary identity and outperform other EC types in promoting the maturation of the dermis and epidermis. These intrinsic characteristics of HDBECs may influence the long-term function of skin grafts.
Authors: Jeffrey S Schechner; Saara K Crane; Feiya Wang; Anya M Szeglin; George Tellides; Marc I Lorber; Alfred L M Bothwell; Jordan S Pober Journal: FASEB J Date: 2003-12 Impact factor: 5.191
Authors: Jen-Tsan Chi; Howard Y Chang; Guttorm Haraldsen; Frode L Jahnsen; Olga G Troyanskaya; Dustin S Chang; Zhen Wang; Stanley G Rockson; Matt van de Rijn; David Botstein; Patrick O Brown Journal: Proc Natl Acad Sci U S A Date: 2003-09-08 Impact factor: 11.205
Authors: Shijun Hu; Ming-Tao Zhao; Fereshteh Jahanbani; Ning-Yi Shao; Won Hee Lee; Haodong Chen; Michael P Snyder; Joseph C Wu Journal: JCI Insight Date: 2016-06-02
Authors: Florian Groeber; Lisa Engelhardt; Julia Lange; Szymon Kurdyn; Freia F Schmid; Christoph Rücker; Stephan Mielke; Heike Walles; Jan Hansmann Journal: ALTEX Date: 2016-05-15 Impact factor: 6.043
Authors: Joanna Kalucka; Laura P M H de Rooij; Jermaine Goveia; Katerina Rohlenova; Sébastien J Dumas; Elda Meta; Nadine V Conchinha; Federico Taverna; Laure-Anne Teuwen; Koen Veys; Melissa García-Caballero; Shawez Khan; Vincent Geldhof; Liliana Sokol; Rongyuan Chen; Lucas Treps; Mila Borri; Pauline de Zeeuw; Charlotte Dubois; Tobias K Karakach; Kim D Falkenberg; Magdalena Parys; Xiangke Yin; Stefan Vinckier; Yuxiang Du; Robert A Fenton; Luc Schoonjans; Mieke Dewerchin; Guy Eelen; Bernard Thienpont; Lin Lin; Lars Bolund; Xuri Li; Yonglun Luo; Peter Carmeliet Journal: Cell Date: 2020-02-13 Impact factor: 41.582
Authors: Steven T Boyce; Richard J Kagan; David G Greenhalgh; Petra Warner; Kevin P Yakuboff; Tina Palmieri; Glenn D Warden Journal: J Trauma Date: 2006-04
Authors: Anne E Carpenter; Thouis R Jones; Michael R Lamprecht; Colin Clarke; In Han Kang; Ola Friman; David A Guertin; Joo Han Chang; Robert A Lindquist; Jason Moffat; Polina Golland; David M Sabatini Journal: Genome Biol Date: 2006-10-31 Impact factor: 13.583