Mesenchymal stem cell implantation in a swine myocardial infarct model: Engraftment and functional effects

Jay G. Shake, Peter J. Gruber, William A. Baumgartner, Guylaine Senechal, Jennifer Meyers, J. Mark Redmond, Mark F. Pittenger, Bradley J. Martin

Research output: Contribution to journalArticlepeer-review

781 Scopus citations

Abstract

Background. A novel therapeutic option for the treatment of acute myocardial infarction involves the use of mesenchymal stem cells (MSCs). The purpose of this study was to investigate whether implantation of autologous MSCs results in sustained engraftment, myogenic differentiation, and improved cardiac function in a swine myocardial infarct model. Methods. MSCs were isolated and expanded from bone marrow aspirates of 14 domestic swine. A 60-minute left anterior descending artery occlusion was used to produce anterior wall infarction. Piezoelectric crystals were placed within the ischemic region for measurement of regional wall thickness and contractile function. Two weeks later animals autologous, Di-I-labeled MSCs (6 × 107) were implanted into the infarct by direct injection. Hemodynamic and functional measurements were obtained weekly until the time of sacrifice. Immunohistochemistry was used to assess MSC engraftment and myogenic differentiation. Results. Microscopic analysis showed robust engraftment of MSCs in all treated animals. Expression of muscle-specific proteins was seen as early as 2 weeks and could be identified in all animals at sacrifice. The degree of contractile dysfunction was significantly attenuated at 4 weeks in animals implanted with MSCs (5.4% ± 2.2% versus -3.37% ± 2.7% in control). In addition, the extent of wall thinning after myocardial infarction was markedly reduced in treated animals. Conclusions. Mesenchymal stem cells are capable of engraftment in host myocardium, demonstrate expression of muscle specific proteins, and may attenuate contractile dysfunction and pathologic thinning in this model of left ventricular wall infarction. MSC cardiomyoplasty may have significant clinical potential in attenuating the pathology associated with myocardial infarction.

Original languageEnglish (US)
Pages (from-to)1919-1926
Number of pages8
JournalAnnals of Thoracic Surgery
Volume73
Issue number6
DOIs
StatePublished - 2002

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

Fingerprint

Dive into the research topics of 'Mesenchymal stem cell implantation in a swine myocardial infarct model: Engraftment and functional effects'. Together they form a unique fingerprint.

Cite this