Document Detail


Percutaneous cell delivery into the heart using hydrogels polymerizing in situ.
MedLine Citation:
PMID:  19558778     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Heart disease is the leading cause of death in the US. Following an acute myocardial infarction, a fibrous, noncontractile scar develops, and results in congestive heart failure in more than 500,000 patients in the US each year. Muscle regeneration and the induction of new vascular growth to treat ischemic disorders of the heart can have significant therapeutic implications. Early studies in patients with chronic ischemic systolic left ventricular dysfunction (SLVD) using skeletal myoblasts or bone marrow-derived cells report improvement in left ventricular ejection function (LVEF) and clinical status, without notable safety issues. Nonetheless, the efficacy of cell transfer for cardiovascular disease is not established, in part due to a lack of control over cell retention, survival, and function following delivery. We studied the use of biocompatible hydrogels polymerizable in situ as a cell delivery vehicle, to improve cell retention, survival, and function following delivery into the ischemic myocardium. The study was conducted using human bone marrow-derived mesenchymal stem cells and fibrin glue, but the methods are applicable to any human stem cells (adult or embryonic) and a wide range of hydrogels. We first evaluated the utility of several commercially available percutaneous catheters for delivery of viscous cell/hydrogel suspensions. Next we characterized the polymerization kinetics of fibrin glue solutions to define the ranges of concentrations compatible with catheter delivery. We then demonstrate the in vivo effectiveness of this preparation and its ability to increase cell retention and survival in a nude rat model of myocardial infarction.
Authors:
Timothy P Martens; Amandine F G Godier; Jonathan J Parks; Leo Q Wan; Michael S Koeckert; George M Eng; Barry I Hudson; Warren Sherman; Gordana Vunjak-Novakovic
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Cell transplantation     Volume:  18     ISSN:  0963-6897     ISO Abbreviation:  Cell Transplant     Publication Date:  2009  
Date Detail:
Created Date:  2009-06-29     Completed Date:  2009-07-15     Revised Date:  2011-01-19    
Medline Journal Info:
Nlm Unique ID:  9208854     Medline TA:  Cell Transplant     Country:  United States    
Other Details:
Languages:  eng     Pagination:  297-304     Citation Subset:  IM    
Affiliation:
Department of Biomedical Engineering, Columbia University, New York, NY, USA; Department of Surgery, Columbia University Medical Center, New York, NY, USA. tpm2102@columbia.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Catheterization
Cell Survival
Fibrin Tissue Adhesive / metabolism
Fibrinogen / metabolism
Humans
Hydrogels / metabolism*
Mesenchymal Stem Cells / cytology,  ultrastructure
Molecular Weight
Myocardium / cytology*
Polymers / metabolism*
Rats
Solutions
Stem Cell Transplantation / methods*
Viscosity
Grant Support
ID/Acronym/Agency:
R01 HL076485/HL/NHLBI NIH HHS; R01 HL076485-04/HL/NHLBI NIH HHS; R01 HL076485-05/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Fibrin Tissue Adhesive; 0/Hydrogels; 0/Polymers; 0/Solutions; 9001-32-5/Fibrinogen
Comments/Corrections

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