An emerging and revolutionary treatment for vascular diseases based on cell therapy for vascular regeneration could provide long-term solutions by delivering stem or progenitor cells to the impaired tissues or blood vessels, potentially repairing them or forming new ones. Studies focusing on human pluripotent stem cells (hPSCs), i.e. human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), have provided insight into the potential of these cells for vascular regeneration and helped identify key molecular events involved in vasculogenesis and angiogenesis. Polymeric hydrogel have been utilized as a tunable matrix to study vascular network morphogenesis. We will focus our work on hyaluronic acid (HA) hydrogels, due to the ability to encapsulate cells and provide a biomimetic environment. We hypothesize that HA hydrogels can be employed to provide critical cues that stimulate tube formation and microvascular network assembly from vascular derivatives of hPSCs, and that such microvasculature can be rapidly incorporated into local vascular microchannels and invest local parenchymal cell populations with functional nutrient networks.
The specific aims are: (1) To Derive Functional ECs and v-SMCs from hiPSCs, (2) To Study Responsive HA Hydrogels for Vascular Morphogenesis, and (3) To Analyze Vascular Network Functionality using an In Ovo Angiogenesis Model

Public Health Relevance

An emerging and revolutionary treatment for vascular diseases based on cell therapy for vascular regeneration could provide long-term solutions by delivering stem or progenitor cells to the impaired tissues or blood vessels, potentially repairing them or forming new ones. We will utilize polymeric hydrogel as a three-dimensional milieu to generate microvasculature bed from human pluripotent stem cells. Our study will provide a profound analysis of 3D human vascular network formation and functionality, and overall relevance of these vascular networks in future clinical applications.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL107938-03
Application #
8471766
Study Section
Biomaterials and Biointerfaces Study Section (BMBI)
Program Officer
Gao, Yunling
Project Start
2011-07-01
Project End
2016-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
3
Fiscal Year
2013
Total Cost
$435,200
Indirect Cost
$116,369
Name
Johns Hopkins University
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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Kusuma, Sravanti; Peijnenburg, Elizabeth; Patel, Parth et al. (2014) Low oxygen tension enhances endothelial fate of human pluripotent stem cells. Arterioscler Thromb Vasc Biol 34:913-20
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Purcell, Brendan P; Lobb, David; Charati, Manoj B et al. (2014) Injectable and bioresponsive hydrogels for on-demand matrix metalloproteinase inhibition. Nat Mater 13:653-61
Gramlich, William M; Kim, Iris L; Burdick, Jason A (2013) Synthesis and orthogonal photopatterning of hyaluronic acid hydrogels with thiol-norbornene chemistry. Biomaterials 34:9803-11
Wanjare, Maureen; Kuo, Frederick; Gerecht, Sharon (2013) Derivation and maturation of synthetic and contractile vascular smooth muscle cells from human pluripotent stem cells. Cardiovasc Res 97:321-30
Kusuma, Sravanti; Shen, Yu-I; Hanjaya-Putra, Donny et al. (2013) Self-organized vascular networks from human pluripotent stem cells in a synthetic matrix. Proc Natl Acad Sci U S A 110:12601-6
Wanjare, Maureen; Kusuma, Sravanti; Gerecht, Sharon (2013) Perivascular cells in blood vessel regeneration. Biotechnol J 8:434-47

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