Recent data, generated as the result of a decade long effort by the Program PI to develop endothelial progenitor cell based therapeutics, provides evidence for the safety and efficacy of autologous progenitor cells for treatment of myocardial and limb ischemia. Specifically two recent human clinical trials have both yielded evidence that autologous human CD34+ cells improve outcome in patients with chronic, refractory ischemia: patients with intractable angina had significant reductions in chest pain and improved exercise tolerance, while patients with critical limb ischemia had reduced amputation rates. While we acknowledge that the final proof of progenitor cell based therapies in phase III studies is forthcoming, it is our belief that the available evidence for bioactivity and potential therapeutic utility of cell based therapy is substantial enough to justify efforts to augment their efficacy by exploiting our knowledge about their biology and further exploring mechanisms that may enhance their safety and therapeutic utility. The overarching goal of this PPG is to advance the therapeutic use of endothelial progenitor cells for the treatment of cardiovascular diseases. This objective will be achieved in the Program by four individual Projects that investigate certain mechanisms of progenitor cell fate, function and dysfunction, and explore novel, nanomaterial based methods to enhance their therapeutic application and by taking advantage of strategically designed Cores that will support each Project. Project 1: Enhancing Progenitor Cell Function using Bioactive Peptide Amphiphiles (Douglas W. Losordo, M.D. and Samuel Stupp Ph.D., Co-I) Project 2: Role of PAI-1 in Cardiovascular Repair and Fibrosis (Douglas E. Vaughan, M.D., PI) Project 3: Characterization of mitochondrial defects in EPCs in diabetes and aging (Hossein Ardehali, M.D., Ph.D., PI) Project 4: Epigenetic modulation of Endothelial Progenitor Cells for Cardiomyogenesis (Raj Kishore, Ph.D., PI) Core A: Small Animal Surgery and Histology (Tsutomu Kume, Ph.D., PI) Core B: Advanced Molecular Imaging (Tom Meade, Ph.D., PI) Core C: FACS Analysis and Cell Sorting (Harris Perlman, Ph.D., PI) Core D;Administrative Core (Douglas Losordo, M.D., PI) PROJECT 1: Peptide Amphiphiles to Augment Progenitor Cell Therapies (Losordo, Douglas W.)

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
3P01HL108795-03S1
Application #
8663728
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Program Officer
Lundberg, Martha
Project Start
2011-09-07
Project End
2016-04-30
Budget Start
2013-06-01
Budget End
2014-04-30
Support Year
3
Fiscal Year
2013
Total Cost
$97,191
Indirect Cost
$34,284
Name
Northwestern University at Chicago
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Kishore, Raj; Khan, Mohsin (2016) More Than Tiny Sacks: Stem Cell Exosomes as Cell-Free Modality for Cardiac Repair. Circ Res 118:330-43
Bharat, Ankit; Bhorade, Sangeeta M; Morales-Nebreda, Luisa et al. (2016) Flow Cytometry Reveals Similarities Between Lung Macrophages in Humans and Mice. Am J Respir Cell Mol Biol 54:147-9
Preslar, Adam T; Tantakitti, Faifan; Park, Kitae et al. (2016) (19)F Magnetic Resonance Imaging Signals from Peptide Amphiphile Nanostructures Are Strongly Affected by Their Shape. ACS Nano 10:7376-84
Archer, Amy M; Saber, Rana; Rose, Shawn et al. (2016) ApoE deficiency exacerbates the development and sustainment of a semi-chronic K/BxN serum transfer-induced arthritis model. J Transl Med 14:170
Nicholls, Francesca J; Rotz, Matthew W; Ghuman, Harmanvir et al. (2016) DNA-gadolinium-gold nanoparticles for in vivo T1 MR imaging of transplanted human neural stem cells. Biomaterials 77:291-306
Nagpal, Varun; Rai, Rahul; Place, Aaron T et al. (2016) Response to Letter Regarding Article, "MiR-125b Is Critical for Fibroblast-to-Myofibroblast Transition and Cardiac Fibrosis". Circulation 133:e714
Nagpal, Varun; Rai, Rahul; Place, Aaron T et al. (2016) MiR-125b Is Critical for Fibroblast-to-Myofibroblast Transition and Cardiac Fibrosis. Circulation 133:291-301
Verma, Suresh K; Garikipati, Venkata Naga Srikanth; Krishnamurthy, Prasanna et al. (2016) IL-10 Accelerates Re-Endothelialization and Inhibits Post-Injury Intimal Hyperplasia following Carotid Artery Denudation. PLoS One 11:e0147615
Jeyabal, Prince; Thandavarayan, Rajarajan A; Joladarashi, Darukeshwara et al. (2016) MicroRNA-9 inhibits hyperglycemia-induced pyroptosis in human ventricular cardiomyocytes by targeting ELAVL1. Biochem Biophys Res Commun 471:423-9
Chang, Hsiang-Chun; Wu, Rongxue; Shang, Meng et al. (2016) Reduction in mitochondrial iron alleviates cardiac damage during injury. EMBO Mol Med 8:247-67

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