Cellular and Molecular Life Sciences

, Volume 76, Issue 3, pp 421–439 | Cite as

Bioengineering human vascular networks: trends and directions in endothelial and perivascular cell sources

  • Kai Wang
  • Ruei-Zeng Lin
  • Juan M. Melero-MartinEmail author


Tissue engineering holds great promise in regenerative medicine. However, the field of tissue engineering faces a myriad of difficulties. A major challenge is the necessity to integrate vascular networks into bioengineered constructs to enable physiological functions including adequate oxygenation, nutrient delivery, and removal of waste products. The last two decades have seen remarkable progress in our collective effort to bioengineer human-specific vascular networks. Studies have included both in vitro and in vivo investigations, and multiple methodologies have found varying degrees of success. What most approaches to bioengineer human vascular networks have in common, however, is the synergistic use of both (1) endothelial cells (ECs)—the cells used to line the lumen of the vascular structures and (2) perivascular cells—usually used to support EC function and provide perivascular stability to the networks. Here, we have highlighted trends in the use of various cellular sources over the last two decades of vascular network bioengineering research. To this end, we comprehensively reviewed all life science and biomedical publications available at the MEDLINE database up to 2018. Emphasis was put on selective studies that definitively used human ECs and were specifically related to bioengineering vascular networks. To facilitate this analysis, all papers were stratified by publication year and then analyzed according to their use of EC and perivascular cell types. This study provides an illustrating discussion on how each alternative source of cells has come to be used in the field. Our intention was to reveal trends and to provide new insights into the trajectory of vascular network bioengineering with regard to cellular sources.


Vascularization Endothelial progenitor cells iPS cells Stem cells Mesenchymal cells Hydrogel Angiogenesis Vasculogenesis 



This work was supported by National Institutes of Health Grants R01AR069038, R01HL128452, and R21AI123883 to J. M.-M.

Author contributions

KW, R-ZL, and JMM-M conceived and designed the project, analyzed the data, discussed and edited the results and wrote the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare no competing financial interests.


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© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Department of Cardiac SurgeryBoston Children’s HospitalBostonUSA
  2. 2.Department of SurgeryHarvard Medical SchoolBostonUSA
  3. 3.Harvard Stem Cell InstituteCambridgeUSA

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