Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 297-304 |
| Number of pages | 8 |
| Journal | Cell Transplantation |
| Volume | 18 |
| Issue number | 3 |
| DOIs | |
| State | Published - Jun 23 2009 |
| Externally published | Yes |
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Keywords
- Heart repair
- Human stem cells
- Hydrogel
ASJC Scopus subject areas
- Cell Biology
- Transplantation
- Biomedical Engineering
Cite this
Percutaneous cell delivery into the heart using hydrogels polymerizing in situ. / Martens, Timothy P.; Godier, Amandine F G; Parks, Jonathan J.; Wan, Leo Q.; Koeckert, Michael S.; Eng, George M.; Hudson, Barry; Sherman, Warren; Vunjak-Novakovic, Gordana.
In: Cell Transplantation, Vol. 18, No. 3, 23.06.2009, p. 297-304.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Percutaneous cell delivery into the heart using hydrogels polymerizing in situ
AU - Martens, Timothy P.
AU - Godier, Amandine F G
AU - Parks, Jonathan J.
AU - Wan, Leo Q.
AU - Koeckert, Michael S.
AU - Eng, George M.
AU - Hudson, Barry
AU - Sherman, Warren
AU - Vunjak-Novakovic, Gordana
PY - 2009/6/23
Y1 - 2009/6/23
N2 - 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.
AB - 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.
KW - Heart repair
KW - Human stem cells
KW - Hydrogel
UR - http://www.scopus.com/inward/record.url?scp=67449085179&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67449085179&partnerID=8YFLogxK
U2 - 10.3727/096368909788534915
DO - 10.3727/096368909788534915
M3 - Article
C2 - 19558778
AN - SCOPUS:67449085179
VL - 18
SP - 297
EP - 304
JO - Cell Transplantation
JF - Cell Transplantation
SN - 0963-6897
IS - 3
ER -