April Stempien-Otero1, Deri Helterline2, Tabitha Plummer2, Stephen Farris2, Andrew Prouse2, Nayak Polissar3, Derek Stanford3, Nahush A Mokadam4. 1. Department of Medicine, University of Washington School of Medicine, Seattle, Washington. Electronic address: april@uw.edu. 2. Department of Medicine, University of Washington School of Medicine, Seattle, Washington. 3. The Mountain-Whisper-Light Statistics, Seattle, Washington. 4. Department of Surgery, University of Washington School of Medicine, Seattle, Washington.
Abstract
BACKGROUND: Clinical trials report improvements in function and perfusion with direct injection of bone marrow cells into the hearts of patients with ischemic cardiomyopathy. Preclinical data suggest these cells improve vascular density, which would be expected to decrease fibrosis and inflammation. OBJECTIVES: The goal of this study was to test the hypothesis that bone marrow stem cells (CD34+) will improve histological measurements of vascularity, fibrosis, and inflammation in human subjects undergoing left ventricular assist device (LVAD) placement as a bridge to cardiac transplantation. METHODS: Subjects with ischemic cardiomyopathy who were scheduled for placement of an LVAD as a bridge to transplantation underwent bone marrow aspiration the day before surgery; the bone marrow was processed into cell fractions (bone marrow mononuclear cells, CD34+, and CD34-). At LVAD implantation, all fractions and a saline control were injected epicardially into predetermined areas and each injection site marked. At the time of transplantation, injected areas were collected. Data were analyzed by paired Student t test comparing the effect of cell fractions injected within each subject. RESULTS: Six subjects completed the study. There were no statistically significant differences in complications with the procedure versus control subjects. Histological analysis indicated that myocardium injected with CD34+ cells had decreased density of endothelial cells compared to saline-injected myocardium. There were no significant differences in fibrosis or inflammation between groups; however, density of activated fibroblasts was decreased in both CD34+ and CD34- injected areas. CONCLUSIONS: Tissue analysis does not support the hypothesis that bone marrow-derived CD34+ cells promote increased vascular tissue in humans with ischemic cardiomyopathy via direct injection.
BACKGROUND: Clinical trials report improvements in function and perfusion with direct injection of bone marrow cells into the hearts of patients with ischemic cardiomyopathy. Preclinical data suggest these cells improve vascular density, which would be expected to decrease fibrosis and inflammation. OBJECTIVES: The goal of this study was to test the hypothesis that bone marrow stem cells (CD34+) will improve histological measurements of vascularity, fibrosis, and inflammation in human subjects undergoing left ventricular assist device (LVAD) placement as a bridge to cardiac transplantation. METHODS: Subjects with ischemic cardiomyopathy who were scheduled for placement of an LVAD as a bridge to transplantation underwent bone marrow aspiration the day before surgery; the bone marrow was processed into cell fractions (bone marrow mononuclear cells, CD34+, and CD34-). At LVAD implantation, all fractions and a saline control were injected epicardially into predetermined areas and each injection site marked. At the time of transplantation, injected areas were collected. Data were analyzed by paired Student t test comparing the effect of cell fractions injected within each subject. RESULTS: Six subjects completed the study. There were no statistically significant differences in complications with the procedure versus control subjects. Histological analysis indicated that myocardium injected with CD34+ cells had decreased density of endothelial cells compared to saline-injected myocardium. There were no significant differences in fibrosis or inflammation between groups; however, density of activated fibroblasts was decreased in both CD34+ and CD34- injected areas. CONCLUSIONS: Tissue analysis does not support the hypothesis that bone marrow-derived CD34+ cells promote increased vascular tissue in humans with ischemic cardiomyopathy via direct injection.
Authors: M Vasa; S Fichtlscherer; A Aicher; K Adler; C Urbich; H Martin; A M Zeiher; S Dimmeler Journal: Circ Res Date: 2001-07-06 Impact factor: 17.367
Authors: Peter A Galie; Duc-Huy T Nguyen; Colin K Choi; Daniel M Cohen; Paul A Janmey; Christopher S Chen Journal: Proc Natl Acad Sci U S A Date: 2014-05-19 Impact factor: 11.205
Authors: Pilar Jimenez-Quevedo; Juan Jose Gonzalez-Ferrer; Manel Sabate; Xavier Garcia-Moll; Roberto Delgado-Bolton; Leopoldo Llorente; Esther Bernardo; Aranzazu Ortega-Pozzi; Rosana Hernandez-Antolin; Fernando Alfonso; Nieves Gonzalo; Javier Escaned; Camino Bañuelos; Ander Regueiro; Pedro Marin; Antonio Fernandez-Ortiz; Barbara Das Neves; Maria Del Trigo; Cristina Fernandez; Teresa Tejerina; Santiago Redondo; Eulogio Garcia; Carlos Macaya Journal: Circ Res Date: 2014-09-17 Impact factor: 17.367
Authors: D Orlic; J Kajstura; S Chimenti; I Jakoniuk; S M Anderson; B Li; J Pickel; R McKay; B Nadal-Ginard; D M Bodine; A Leri; P Anversa Journal: Nature Date: 2001-04-05 Impact factor: 49.962
Authors: Thomas J Povsic; Candice Junge; Adel Nada; Richard A Schatz; Robert A Harrington; Charles J Davidson; F David Fortuin; Dean J Kereiakes; Farrell O Mendelsohn; Warren Sherman; Gary L Schaer; Christopher J White; Duncan Stewart; Kenneth Story; Douglas W Losordo; Timothy D Henry Journal: Am Heart J Date: 2013-04-19 Impact factor: 4.749
Authors: James K Kirklin; David C Naftel; Robert L Kormos; Lynne W Stevenson; Francis D Pagani; Marissa A Miller; J T Baldwin; J Timothy Baldwin; James B Young Journal: J Heart Lung Transplant Date: 2013-02 Impact factor: 10.247
Authors: Alan W Heldman; Darcy L DiFede; Joel E Fishman; Juan P Zambrano; Barry H Trachtenberg; Vasileios Karantalis; Muzammil Mushtaq; Adam R Williams; Viky Y Suncion; Ian K McNiece; Eduard Ghersin; Victor Soto; Gustavo Lopera; Roberto Miki; Howard Willens; Robert Hendel; Raul Mitrani; Pradip Pattany; Gary Feigenbaum; Behzad Oskouei; John Byrnes; Maureen H Lowery; Julio Sierra; Mariesty V Pujol; Cindy Delgado; Phillip J Gonzalez; Jose E Rodriguez; Luiza Lima Bagno; Didier Rouy; Peter Altman; Cheryl Wong Po Foo; Jose da Silva; Erica Anderson; Richard Schwarz; Adam Mendizabal; Joshua M Hare Journal: JAMA Date: 2014-01-01 Impact factor: 56.272
Authors: G Robin Barclay; Olga Tura; Kay Samuel; Patrick Wf Hadoke; Nicholas L Mills; David E Newby; Marc L Turner Journal: Stem Cell Res Ther Date: 2012-07-03 Impact factor: 6.832
Authors: Yagna P R Jarajapu; Sugata Hazra; Mark Segal; Sergio Li Calzi; Sergio LiCalzi; Chandra Jadhao; Chandra Jhadao; Kevin Qian; Sayak K Mitter; Mohan K Raizada; Michael E Boulton; Maria B Grant Journal: PLoS One Date: 2014-04-08 Impact factor: 3.240
Authors: Agata Jedrzejewska; Alicja Braczko; Ada Kawecka; Marcin Hellmann; Piotr Siondalski; Ewa Slominska; Barbara Kutryb-Zajac; Magdi H Yacoub; Ryszard T Smolenski Journal: Int J Mol Sci Date: 2022-08-31 Impact factor: 6.208
Authors: Muhammad Y Qureshi; Allison K Cabalka; Shakila P Khan; Donald J Hagler; Dawit T Haile; Bryan C Cannon; Timothy M Olson; Susana Cantero-Peral; Allan B Dietz; Darcie J Radel; Nathan W Taggart; Angela M Kelle; Vilmarie Rodriguez; Joseph A Dearani; Patrick W O'Leary Journal: Mayo Clin Proc Innov Qual Outcomes Date: 2017-08-02