Presentation on theme: "Kai Pinkernell, MD 4 th Int. Symp. Stem Cell Therapy & CV Biology Madrid, Spain 26 th of April 2007 Adipose Derived Stem Cell Therapy in Cardiovascular."— Presentation transcript:
Kai Pinkernell, MD 4 th Int. Symp. Stem Cell Therapy & CV Biology Madrid, Spain 26 th of April 2007 Adipose Derived Stem Cell Therapy in Cardiovascular Disease.
Adipogenic Osteogenic Chondrogenic Neurogenic Adipose Tissue Derived Stem Cells - The Concept GalC AP Oil Red-O Alcian Blue Zuk et al. Microbiology of the Cell 2003 Zuk et al. Tissue Engineering 2001 - Easily accessible - Large amounts available
Liposuction of Adipose Tissue How to Obtain Adipose Derived Cells? Washing media Liquid fat Collagen/ Adipocytes/ Debris Cell pellet/ erythrocytes Adipose Derived Cells after Enzyme Digestion + Centrifugation Right picture from Tulane University
ADRCs (top row) in a tube formation assay using Antibodies against CD31(red), von-Willebrandt factor (vWF, green) and DAPI (blue) as a nuclear stain. Fibroblasts (bottom row) were used as a control. ‘Fresh’ ADCs Tubule Formation ADRC Fibro- blasts
Angiogenesis: ADRC Participate in Vessel Formation CD31 SMA Von VIII SMM M. Zuh Gel Plug (0.1 mL, 0.5 Mio.) of RosaLacZ ADRCs into collagen gel (no growth factors) in SCID mice, 3 weeks later.
Angiogenic Potential of ADCs Miranville et al. Circ 2004; 110;349-355
Mouse Hindlimb Ischemia Model 24 hour ischemia, then i.v. infusion of 0.5 Mio human cells; murine athymics Miranville et al. Circ 2004; 110;349-355
Plasticity of Human Adipose Lineage Cells Toward Endothelial Cells Planat-Benard, et al., Circulation (2004) CD31
Summary of Benefits of ADCs in Cardiovascular Diseases Hindlimb Models Increase in perfusion Cardiac Disease Models No arrhythmias or other cell related mortality/morbidity Improvement in function Increased perfusion Increased wall thickness
Objective: Safety and feasibility in patients with non-revascularizable ischemia Center: Universitario Gregorio Marañon in Madrid, PI’s Fernandez-Avilés and Perin (Texas Heart Institute) Trial design & inclusion: ADRCs delivered by intramyocardial injection via NOGA™ Prospective, randomized, placebo-controlled, double-blind, dose escalation trial Measures to include ejection fraction, perfusion, max vO 2, & 6- minute walk Up to 36 patients 6 month follow up Currently enrolling PRECISE: Chronic Myocardial Ischemia Trial
Objective: Safety and feasibility in STEMI patients Center: Thoraxcenter, Erasmus University Rotterdam, PI Patrick Serruys Proposed trial design & inclusion: Intra-coronary delivery of ADRCs Prospective, randomized, placebo-controlled, double-blind, dose escalation trial Measures to include ejection fraction, perfusion & wall motion Up to 48 patients 6-month follow-up Begin enrolling Q2 2007 APOLLO: Acute Myocardial Infarction Trial