Cath Lab Digest - March 2008 - (Page 34)

34 RESEARCH UPDATE MARCH 2008 Table 1. Sources of cell types Cell type Abbreviation Origin Bone-derived cell BMPC Bone marrow Skeletal myoblast SM Adult skeletal muscle Cardiomyocyte progenitor cell CMPC Adult or fetal heart Cardiac stem cell CSC Heart Embryonic stem cell ESC Blastocyst stage embryos Endothelial progenitor cell/ EPC Bone marrow/ endothelial precursor cell peripheral blood adhesion molecules (ALCAM/ CD44) and antigens.10,11 Studies have suggested that MSC are themselves capable of multipotency, with differentiation into chondrocytes, osteoblasts, astrocytes, neurons, skeletal muscle, and notably, cardiomyocytes.12-14 2. Skeletal myoblasts (SM): SM or satellite cells represent an autologous source of progenitor cells that normally lie in a quiescent state under the basal membrane of mature muscular fibers and normally mediate regeneration of skeletal muscle. Myoblasts were the first cell type to be used clinically for cardiac repair owing to their preclinical efficacy, autologous availability, ability to be amplified in vitro, and relatively good survival after implantation. To date, SMs have only been used in trials of heart failure, and not for acute MI, owing to the method of preparation and route of delivery. 3. Cardiac stem cells (CSC): These newly described stem cells from the heart are multipotent, giving rise to endothelial cells, smooth muscle cells, and functional cardiomyocytes. In addition, they supported myocardial regeneration after infarction in a rat model. Future research on CSC will help to answer these questions and may provide the means for efficient heart regeneration.15 4. Embryonic stem cells (ESC): ESCs are derived from the inner cell mass of blastocyst stage of the embryos; they grow indefinitely in an undifferentiated state while retaining the ability to differentiate to all cell types in the adult body, including cardiomyocytes.16 Because of unresolved ethical and legal issues, concerns about tumorogenicity and arrhythmogenecity of the cells, and the need to use allogeneic cells for transplantation, ESC have not been investigated broadly and will not be used clinically in the near future. 5. Umbilical cord stem cells (UCSC): UCSC have shown to possess a potential for plasticity at least similar to, most likely greater than human adult stem cells; also, their differentiation may also lead to mobilization of endogenous progenitor cells, all of which affect remodeling. Source of different stem cell types 1. Bone marrow–derived stem cells (BMC): Although the ability of BMC to transdifferentiate into cardiomyocytes remains highly controversial, much of the recent progress in regenerative cardiovascular research has been achieved using BMC populations, including hematopoietic stem cells (HSC), mesenchymal stem cells (MSC), and endothelial progenitor cells (EPC). Despite the failure of studies to definitely prove differentiation of HSC into cardiomyocytes in vitro, several studies in mice have demonstrated the potential of HSC to differentiate into cardiomyocytes or vascular cells after cardiac injury in vivo.6-8 EPC express the hematopoietic stem cell markers (CD133 and CD34 and the endothelial marker Flk-1 (VEGFR-2).9 EPC can be isolated directly from the bone marrow or from the peripheral circulation. MSC lack the typical hematopoietic antigens (c-kit, CD45, CD34, CD14), but express specific Table 2. Selected clinical trials of autologous skeletal myoblasts in cardiomyopathy Study Menasche et al. (2003) Herreros et al. (2003) Simniak et al. (2004) Dib et al. (2005) MAGIC (2006) Design (n) Series (10) Series (12) Series (10) Series (30) RCT4, double-blind Cell type Myoblasts Myoblasts Myoblasts Myoblasts Myoblasts Route Epicardial during CABG5 Epicadial during CABG5 Epicadial during CABG5 Epicadial CABG5+LVAD2 Epicadial during CABG5 Follow up 5-17.5 months 3 months 6 months 2 years Outcomes Improved NYHA3 Improved LVEF1 Improved LVEF1 Improved LVEF1 Improved LVEF1 Early termination No effect on EF + LV remodeling 1 LVEF, Left ventricular ejection fraction; 2LVAD, left ventricular assist device; 3NYHA, New York Heart Association functional class; 4RCT, randomized clinical trial; 5CABG, coronary artery bypass grafting Table 3. Selected clinical trials of bone marrow-derived stem cells Study BOOST TOPCARE-AMI Janssens et al. ASTAMI REPAIR-AMI REVIVAL-2 TOPCARE-CHD MAGIC Cell-3-4DES 1 Design(n) Randomized clinical trial (RCT), open label (60) Randomized (59) RCT, double-blind (67) RCT, double-blind (100) RCT, double-blind (204) RCT, double-blind (114) RCT, crossover (75) RCT (96) Cell type BM-MNC1 BM-MNC1 vs. CPC 2 BM-MNC1 BM-MNC1 BM-MNC1 G-CSF and PBSC3 BM-MNC1 vs. CPC2 G-CSF and PBSC3 Route Intracoronary Intracoronary Intracoronary Intracoronary Intracoronary Mobilization Intracoronary Intracoronary Outcomes Improvement of LVEF5 at 6 months Improved LVEF5 and perfusion Reduced infract size NO benefit Improved LVEF5 No effect on LVEF5 Improvement of LVEF5 Improvement of LVEF5 BM-MNC, Bone marrow mononuclear cell; 2CPC, circulating progenitor cell; 3PBSC, peripheral bone marrow stem cells; 4DES, Drug-eluting stent; 5LVEF, Left ventricular ejection fraction

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Cath Lab Digest - March 2008 Are You Being Paid Fair Market Value in 2008? A Cardiac Cath Lab Professionals Survey by Cath Lab Digest and the Society of Invasive Cardiovascular Professionals Saint Joseph’s Hospital Invasive Imaging Tools for Optimizing Coronary Stent Deployment Contents Clinical Editor’s Corner A Workflow Revolution in Cath Lab Reporting Advantages of a New Digital Lab at Baystate Medical Center Cardiac Computed Tomography: What Does it Mean for the Cath Lab? The Latest in Cardiac Magnetic Resonance Imaging (MRI) Cellular Cardiomyoplasty and Cardiac Regeneration Intravascular Ultrasound in the Cath Lab: A Powerful — and Underutilized — Tool to Improve Patient Outcomes The Stentplus™ Patient Success Program Cardiac Cath Lab Clutter — or, Spring into Action! Groin Bleeds and Other Hemorrhagic Complications of Cardiac Catheterization: A List of Relevant Issues Ask the Clinical Instructor: A Q&A Column for Those New to the Cath Lab What Do You Think? Experience with a New Guidewire: The Terumo Runthrough NS The Ostial Pro™ Stent Positioning System: Perfecting Aorto-Ostial Stent Placement Precious Minutes The Ten-Minute Interview with…Mark Bowles, BSN, CCRN Vascular Care in the Cath Lab: Planning a Smooth Transition Cath Laughs CMS 2008 OPPS Final Rule Review An Extensive Set of Review Courses for the CCI Basic Science, Non-Invasive Echocardiography and Vascular, and ARDMS Ultrasound Exams Meetings Calendar CEU Education Center Clinical & Industry News STEMI Interventions Classifieds Advertisers Index

Cath Lab Digest - March 2008

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