Influence of endothelial progenitor cells on inflammation-associated stroke vasculome

Project: Research


  • Sandra A Acosta (PI)


Stroke is the number one cause of disability in the adult population and the fourth leading cause of death in the United States. Each year in the United States, an estimated 795,000 people suffer from stroke and therapeutic interventions are limited with only one FDA-approved drug for ischemic stroke; namely tissue plasminogen activator or tPA. Due to its narrow therapeutic window of only 4.5 hours of ischemic stroke, tPA can only be administered to approximately 5% of ischemic patients due to hemorrhagic complications. Therefore, a safe and effective therapeutic intervention is urgently needed for ischemic stroke patients. Recently, the concept of brain physiology and disease has adopted a more integrative approach whereby different systems i.e. vascular system and inflammatory system interact and crosstalk. Recent novel findings revealed that cerebral endothelium can also secrete molecules that may regulate disease processes following ischemic stroke; namely stroke vasculome. Analysis of the stroke vasculome revealed that there is an upregulation of the following genes Brahma (BRM), IkB (also called NFkB inhibitor), foxfl, and ITIH-5, apcdd1, ATP2b2, and Axin2. Based on these observations, we are interested in the concept of stem cell based therapy in modulating the inflammation-associated stroke vasculome. Endothelial progenitor cells (EPCs) are an attractive therapeutic intervention for vascular repair in ischemic stroke because they are constantly migrating from the bone marrow to the brain to facilitate endothelium repair during physiological and pathophysiological scenarios and to keep CNS and vascular homeostasis. However, to our knowledge, no study has investigated the potential of EPCs in attenuating the inflammation-associated vasculome following ischemic stroke. Altogether, EPC transplantation stands as a potent therapeutic intervention for regenerative medicine in ischemic stroke pathology and other neurodegenerative vascular diseases. This proposal addresses the objective of the AHA Funding Opportunity Announcement Fellowship 16POST27790076 (GSA Summer 2015 Postdoctoral Fellowship) to enhance the current knowledge about cardiovascular disease and stroke, and to develop and improve therapies in order to build healthier lives for those suffering from cardiovascular diseases and stroke.
Award amount$101,912.00
Award date01/01/2016
Program typePostdoctoral Fellowship
Award ID16POST27790076
Effective start/end date01/01/201612/31/2017