Person:
Zangi, Lior

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Zangi

First Name

Lior

Name

Zangi, Lior

Filters

20132

Settings

Author's Publications: search.filters.isAuthorOfPublication.d536c6dc-3b28-4a3e-a8fc-81ed0c565171

Search Results

Now showing 1 - 2 of 2
  • Thumbnail Image
    Publication
    Driving vascular endothelial cell fate of human multipotent Isl1+ heart progenitors with VEGF modified mRNA
    (Nature Publishing Group, 2013) Lui, Kathy; Zangi, Lior; Silva, Eduardo A; Bu, Lei; Sahara, Makoto; Li, Ronald A; Mooney, David; Chien, Kenneth R
    Distinct families of multipotent heart progenitors play a central role in the generation of diverse cardiac, smooth muscle and endothelial cell lineages during mammalian cardiogenesis. The identification of precise paracrine signals that drive the cell-fate decision of these multipotent progenitors, and the development of novel approaches to deliver these signals in vivo, are critical steps towards unlocking their regenerative therapeutic potential. Herein, we have identified a family of human cardiac endothelial intermediates located in outflow tract of the early human fetal hearts (OFT-ECs), characterized by coexpression of Isl1 and CD144/vWF. By comparing angiocrine factors expressed by the human OFT-ECs and non-cardiac ECs, vascular endothelial growth factor (VEGF)-A was identified as the most abundantly expressed factor, and clonal assays documented its ability to drive endothelial specification of human embryonic stem cell (ESC)-derived Isl1+ progenitors in a VEGF receptor-dependent manner. Human Isl1-ECs (endothelial cells differentiated from hESC-derived ISL1+ progenitors) resemble OFT-ECs in terms of expression of the cardiac endothelial progenitor- and endocardial cell-specific genes, confirming their organ specificity. To determine whether VEGF-A might serve as an in vivo cell-fate switch for human ESC-derived Isl1-ECs, we established a novel approach using chemically modified mRNA as a platform for transient, yet highly efficient expression of paracrine factors in cardiovascular progenitors. Overexpression of VEGF-A promotes not only the endothelial specification but also engraftment, proliferation and survival (reduced apoptosis) of the human Isl1+ progenitors in vivo. The large-scale derivation of cardiac-specific human Isl1-ECs from human pluripotent stem cells, coupled with the ability to drive endothelial specification, engraftment, and survival following transplantation, suggest a novel strategy for vascular regeneration in the heart.
  • Thumbnail Image
    Publication
    Modified mRNA directs the fate of heart progenitor cells and induces vascular regeneration after myocardial infarction
    (Nature Publishing Group, 2013) Zangi, Lior; Lui, Kathy O; von Gise, Alexander; Ma, Qing; Ebina, Wataru; Ptaszek, Leon; Später, Daniela; Xu, Huansheng; Tabebordbar, M; Gorbatov, Rostic; Sena, Brena; Nahrendorf, Matthias; Briscoe, David; Li, Ronald A; Wagers, Amy; Rossi, Derrick; Pu, William; Chien, Kenneth R
    In a cell-free approach to regenerative therapeutics, transient application of paracrine factors in vivo could be used to alter the behavior and fate of progenitor cells to achieve sustained clinical benefits. Here we show that intramyocardial injection of synthetic modified RNA (modRNA) encoding human vascular endothelial growth factor-A (VEGF-A) results in the expansion and directed differentiation of endogenous heart progenitors in a mouse myocardial infarction model. VEGF-A modRNA markedly improved heart function and enhanced long-term survival of recipients. This improvement was in part due to mobilization of epicardial progenitor cells and redirection of their differentiation toward cardiovascular cell types. Direct in vivo comparison with DNA vectors and temporal control with VEGF inhibitors revealed the greatly increased efficacy of pulse-like delivery of VEGF-A. Our results suggest that modRNA is a versatile approach for expressing paracrine factors as cell fate switches to control progenitor cell fate and thereby enhance long-term organ repair.