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
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.
|Kusuma, Sravanti; Smith, Quinton; Facklam, Amanda et al. (2017) Micropattern size-dependent endothelial differentiation from a human induced pluripotent stem cell line. J Tissue Eng Regen Med 11:855-861|
|Caliari, Steven R; Vega, Sebastián L; Kwon, Michelle et al. (2016) Dimensionality and spreading influence MSC YAP/TAZ signaling in hydrogel environments. Biomaterials 103:314-323|
|Shen, Yu-I; Cho, Hongkwan; Papa, Arianne E et al. (2016) Engineered human vascularized constructs accelerate diabetic wound healing. Biomaterials 102:107-19|
|Rodell, Christopher B; Highley, Christopher B; Chen, Minna H et al. (2016) Evolution of hierarchical porous structures in supramolecular guest-host hydrogels. Soft Matter 12:7839-7847|
|Hielscher, Abigail; Ellis, Kim; Qiu, Connie et al. (2016) Fibronectin Deposition Participates in Extracellular Matrix Assembly and Vascular Morphogenesis. PLoS One 11:e0147600|
|Kusuma, Sravanti; Gerecht, Sharon (2016) Derivation of Endothelial Cells and Pericytes from Human Pluripotent Stem Cells. Methods Mol Biol 1307:213-22|
|Shen, Yu-I; Song, Hyun-Ho Greco; Papa, Arianne et al. (2015) Acellular Hydrogels for Regenerative Burn Wound Healing: Translation from a Porcine Model. J Invest Dermatol 135:2519-2529|
|Wade, Ryan J; Bassin, Ethan J; Gramlich, William M et al. (2015) Nanofibrous hydrogels with spatially patterned biochemical signals to control cell behavior. Adv Mater 27:1356-62|
|Wanjare, Maureen; Agarwal, Nayan; Gerecht, Sharon (2015) Biomechanical strain induces elastin and collagen production in human pluripotent stem cell-derived vascular smooth muscle cells. Am J Physiol Cell Physiol 309:C271-81|
|Mealy, Joshua E; Rodell, Christopher B; Burdick, Jason A (2015) Sustained Small Molecule Delivery from Injectable Hyaluronic Acid Hydrogels through Host-Guest Mediated Retention. J Mater Chem B 3:8010-8019|
Showing the most recent 10 out of 44 publications