Percutaneous cell delivery into the heart using hydrogels polymerizing in situ

Timothy P. Martens, Amandine F G Godier, Jonathan J. Parks, Leo Q. Wan, Michael S. Koeckert, George M. Eng, Barry Hudson, Warren Sherman, Gordana Vunjak-Novakovic

Research output: Contribution to journalArticle

105 Citations (Scopus)

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 languageEnglish
Pages (from-to)297-304
Number of pages8
JournalCell Transplantation
Volume18
Issue number3
DOIs
StatePublished - Jun 23 2009
Externally publishedYes

Fingerprint

Hydrogels
Cell Survival
Fibrin Tissue Adhesive
Glues
Catheters
Stem cells
Bone
Myocardial Infarction
Skeletal Myoblasts
Nude Rats
Adult Stem Cells
Hydrogel
Left Ventricular Dysfunction
Embryonic Stem Cells
Mesenchymal Stromal Cells
Left Ventricular Function
Polymerization
Bone Marrow Cells
Cicatrix
Blood Vessels

Keywords

  • Heart repair
  • Human stem cells
  • Hydrogel

ASJC Scopus subject areas

  • Cell Biology
  • Transplantation
  • Biomedical Engineering

Cite this

Martens, T. P., Godier, A. F. G., Parks, J. J., Wan, L. Q., Koeckert, M. S., Eng, G. M., ... Vunjak-Novakovic, G. (2009). Percutaneous cell delivery into the heart using hydrogels polymerizing in situ. Cell Transplantation, 18(3), 297-304. https://doi.org/10.3727/096368909788534915

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 journalArticle

Martens, TP, Godier, AFG, Parks, JJ, Wan, LQ, Koeckert, MS, Eng, GM, Hudson, B, Sherman, W & Vunjak-Novakovic, G 2009, 'Percutaneous cell delivery into the heart using hydrogels polymerizing in situ', Cell Transplantation, vol. 18, no. 3, pp. 297-304. https://doi.org/10.3727/096368909788534915
Martens TP, Godier AFG, Parks JJ, Wan LQ, Koeckert MS, Eng GM et al. Percutaneous cell delivery into the heart using hydrogels polymerizing in situ. Cell Transplantation. 2009 Jun 23;18(3):297-304. https://doi.org/10.3727/096368909788534915
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. / Percutaneous cell delivery into the heart using hydrogels polymerizing in situ. In: Cell Transplantation. 2009 ; Vol. 18, No. 3. pp. 297-304.
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