Open AccessEnhancing engineered vascular networks in vitro and in vivo: The effects of IGF 1 on vascular development and durability
Author(s) -
Friedrich Claudia C.,
Lin Yunfeng,
Krannich Alexander,
Wu Yinan,
Vacanti Joseph P.,
Neville Craig M.
Publication year - 2018
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12387
Subject(s) - vasculogenesis , in vivo , tissue engineering , mesenchymal stem cell , microbiology and biotechnology , in vitro , regenerative medicine , regeneration (biology) , umbilical vein , biology , stem cell , progenitor cell , immunology , biomedical engineering , medicine , biochemistry
Objectives Creation of functional, durable vasculature remains an important goal within the field of regenerative medicine. Engineered biological vasculature has the potential to restore or improve human tissue function. We hypothesized that the pleotropic effects of insulin‐like growth factor 1 ( IGF 1) would enhance the engineering of capillary‐like vasculature. Materials and methods The impact of IGF 1 upon vasculogenesis was examined in in vitro cultures for a period of up to 40 days and as subcutaneous implants within immunodeficient mice. Co‐cultures of human umbilical vein endothelial cells and human bone marrow‐derived mesenchymal stem cells in collagen‐fibronectin hydrogels were supplemented with either recombinant IGF 1 protein or genetically engineered cells to provide sustained IGF 1. Morphometric analysis was performed on the vascular networks that formed in four concentrations of IGF 1. Results IGF 1 supplementation significantly enhanced de novo vasculogenesis both in vitro and in vivo. Effects were long‐term as they lasted the duration of the study period, and included network density, vessel length, and diameter. Bifurcation density was not affected. However, the highest concentrations of IGF 1 tested were either ineffective or even deleterious. Sustained IGF 1 delivery was required in vivo as the inclusion of recombinant IGF 1 protein had minimal impact. Conclusion IGF 1 supplementation can be used to produce neovasculature with significantly enhanced network density and durability. Its use is a promising methodology for engineering de novo vasculature to support regeneration of functional tissue.