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An Injectable and Drug-loaded Supramolecular Hydrogel for Local Catheter Injection into the Pig Heart
Published on: June 7, 2015
Percutaneous cell delivery into the heart using hydrogels polymerizing in situ
Timothy P Martens1, Amandine F G Godier, Jonathan J Parks
1Department of Biomedical Engineering, Columbia University, New York, NY, USA; Department of Surgery, Columbia University Medical Center, New York, NY, USA. tpm2102@columbia.edu
Insights
Biocompatible hydrogels improve stem cell retention and survival after heart attack. This novel delivery method enhances cell therapy for myocardial infarction, offering hope for treating heart failure.
Area of Science:
- Regenerative Medicine
- Biomaterials Science
- Cardiovascular Research
Background:
- Heart disease is a leading cause of death, with myocardial infarction leading to heart failure.
- Current cell therapies for heart disease show promise but lack consistent efficacy due to poor cell retention and survival.
- Improving cell delivery and retention is crucial for successful cardiac regenerative medicine.
Purpose of the Study:
- To develop and evaluate in situ polymerizable biocompatible hydrogels as a delivery vehicle for stem cells in ischemic myocardium.
- To enhance cell retention, survival, and function following delivery into the heart.
- To assess the feasibility of using percutaneous catheters for delivering cell-hydrogel suspensions.
Main Methods:
- Human bone marrow-derived mesenchymal stem cells were combined with fibrin glue.
- Commercial percutaneous catheters were evaluated for delivering viscous cell/hydrogel suspensions.
- Fibrin glue polymerization kinetics were characterized for catheter compatibility.
- In vivo effectiveness was demonstrated in a nude rat model of myocardial infarction.
Main Results:
- Biocompatible hydrogels, specifically fibrin glue, were successfully delivered via percutaneous catheters.
- Hydrogel polymerization kinetics were defined for optimal catheter-based delivery.
- The hydrogel delivery system significantly increased cell retention and survival in the infarcted myocardium.
- This approach shows potential for improving cell-based therapies for heart disease.
Conclusions:
- In situ polymerizable hydrogels serve as effective vehicles for delivering stem cells to the ischemic heart.
- This method enhances cell retention and survival, addressing a key limitation in cardiac cell therapy.
- The findings support the development of improved cell delivery strategies for treating heart failure post-myocardial infarction.
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.
