Bioengineering – Vascular Biology – Regenerative Medicine
Research overview
Engineered tissues live or die by their blood supply. A tissue can be built with the right cells and architecture, but without a functional vascular network to deliver oxygen and nutrients, it cannot survive or integrate once implanted. This single constraint limits much of what regenerative medicine can achieve today.
Our laboratory works to solve it. We apply bioengineering principles to understand how vascular networks form, and how the vasculature governs the engraftment and function of human stem cells. Our goal is to make reliable vascularization a foundation that tissue engineering and cell therapies can build on, rather than a barrier they run into.
Two recent advances illustrate our approach. We discovered that vascular cells naturally exchange mitochondria with one another, and we harnessed this biology as a mitochondrial transplantation strategy that improves the fitness of vascular cells and their capacity to engraft and form functional blood vessels in vivo. Separately, we developed a method to generate functional vascular organoids from human induced pluripotent stem cells in just five days; upon implantation, these organoids restore blood flow and markedly reduce tissue damage in preclinical models of ischemia. Together, these findings open new routes to vascularizing engineered tissues and strengthening cell-based therapies.
Selected publications
Rapid generation of functional vascular organoids via simultaneous transcription factor activation of endothelial and mural lineages
Gong L, Zhang Y, Zhu Y, Lee U, Luo AC, Li X, Wang X, Chen D, Pu WT, Lin RZ, Ma M, Cui M, Chen K, Wang K *, Melero-Martin JM *
Cell Stem Cell 2025; Jun 13. doi:10.1016/j.stem.2025.05.014. Online ahead of print.
PDF: Gong et al., 2025
Mitochondrial transfer mediates endothelial cell engraftment through mitophagy
Lin RZ, Im GB, Luo AC, Zhu Y, Hong X, Neumeyer J, Tang HW, Perrimon N, Melero-Martin JM
Nature 2024;629(8012):660-668
PDF: Lin et al., 2024
Robust differentiation of human pluripotent stem cells into mural progenitor cells via transient activation of NKX3.1
Lee U †, Zhang Y †, Zhu Y, Luo AC, Gong L, Tremmel DM, Kim Y, Villarreal VS, Wang X, Lin RZ, Cui M, Ma M, Yuan K, Wang K *, Chen K *, Melero-Martin JM *
Nat Commun 2024;15:8392
PDF: Lee et al., 2024
Robust differentiation of human pluripotent stem cells into endothelial cells via temporal modulation of ETV2 with modified mRNA
Wang K, Lin RZ, Hong X, Ng AH, Lee CN, Neumeyer J, Wang G, Wang X, Ma M, Pu WT, Church GM, Melero-Martin JM
Sci Adv 2020;6(30):eaba7606
PDF: Wang et al., 2020
Bioengineering hemophilia A-specific microvascular grafts for delivery of full-length factor VIII into the bloodstream
Neumeyer J, Lin RZ, Wang K, Hong X, Hua T, Croteau SE, Neufeld EJ, Melero-Martin JM
Blood Adv 2019;3(24):4166-4176
PDF: Neumeyer et al., 2019
Host non-inflammatory neutrophils mediate the engraftment of bioengineered vascular networks
Lin RZ, Lee CN, Moreno-Luna R, Neumeyer J, Piekarski B, Zhou P, Moses MA, Sachdev M, Pu WT, Emani S, Melero-Martin JM
Nat Biomed Eng 2017;1:0081
Editorial Commentary
Editorial News and Views
PDF: Lin et al., 2017