title: Concise Review: Review and Perspective of Cell Dosage and Routes of Administration From Preclinical and Clinical Studies of Stem Cell Therapy for Heart Disease.
abstract: An important stage in the development of any new therapeutic agent is establishment of the optimal dosage and route of administration. This can be particularly challenging when the treatment is a biologic agent that might exert its therapeutic effects via complex or poorly understood mechanisms. Multiple preclinical and clinical studies have shown paradoxical results, with inconsistent findings regarding the relationship between the cell dose and clinical benefit. Such phenomena can, at least in part, be attributed to variations in cell dosing or concentration and the route of administration (ROA). Although clinical trials of cell-based therapy for cardiovascular disease began more than a decade ago, specification of the optimal dosage and ROA has not been established. The present review summarizes what has been learned regarding the optimal cell dosage and ROA from preclinical and clinical studies of stem cell therapy for heart disease and offers a perspective on future directions. Significance: Preclinical and clinical studies on cell-based therapy for cardiovascular disease have shown inconsistent results, in part because of variations in study-specific dosages and/or routes of administration (ROA). Future preclinical studies and smaller clinical trials implementing cell-dose and ROA comparisons are warranted before proceeding to pivotal trials.
authors.affiliation: Interdisciplinary Stem Cell Institute, Miller School of Medicine, University of Miami, Miami, Florida, USA Department of Surgery, Miller School of Medicine, University of Miami, Miami, Florida, USA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Golpanian
authors.affiliation: Interdisciplinary Stem Cell Institute, Miller School of Medicine, University of Miami, Miami, Florida, USA Department of Medicine, Miller School of Medicine, University of Miami, Miami, Florida, USA.
authors.forename: Ivonne H
authors.initials: IH
authors.lastname: Schulman
authors.affiliation: National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Ray F
authors.initials: RF
authors.lastname: Ebert
authors.affiliation: Interdisciplinary Stem Cell Institute, Miller School of Medicine, University of Miami, Miami, Florida, USA Department of Medicine, Miller School of Medicine, University of Miami, Miami, Florida, USA.
authors.forename: Alan W
authors.initials: AW
authors.lastname: Heldman
authors.affiliation: Interdisciplinary Stem Cell Institute, Miller School of Medicine, University of Miami, Miami, Florida, USA.
authors.forename: Darcy L
authors.initials: DL
authors.lastname: DiFede
authors.affiliation: School of Medicine, Stanford University, Stanford, California, USA.
authors.forename: Phillip C
authors.initials: PC
authors.lastname: Yang
authors.affiliation: School of Medicine, Stanford University, Stanford, California, USA.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Wu
authors.affiliation: School of Medicine, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Bolli
authors.affiliation: Texas Heart Institute, CHI St. Luke's Health, Baylor College of Medicine Medical Center, Houston, Texas, USA.
authors.forename: Emerson C
authors.initials: EC
authors.lastname: Perin
authors.affiliation: School of Public Health, University of Texas Health Science Center, Houston, Texas, USA lemmoye@msn.com.
authors.forename: Lem
authors.initials: L
authors.lastname: Moyé
authors.affiliation: School of Medicine, University of Kansas, Kansas City, Kansas, USA.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Simari
authors.affiliation: Interdisciplinary Stem Cell Institute, Miller School of Medicine, University of Miami, Miami, Florida, USA.
authors.forename: Ariel
authors.initials: A
authors.lastname: Wolf
authors.affiliation: Interdisciplinary Stem Cell Institute, Miller School of Medicine, University of Miami, Miami, Florida, USA Department of Medicine, Miller School of Medicine, University of Miami, Miami, Florida, USA.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Hare
mesh_terms: D000818:Animals; D062906:Cardiac Catheters; D002452:Cell Count; D004285:Dogs; D005069:Evaluation Studies as Topic; D006331:Heart Diseases / Q000473:pathology / Q000628:therapy*; D006801:Humans; D015552:Injections, Intralesional; D007275:Injections, Intravenous; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous
keywords: Cardiovascular disease; Cell dosage; Route of administration; Stem cell