TY - JOUR
T1 - Mesenchymal stem cell implantation in a swine myocardial infarct model
T2 - Engraftment and functional effects
AU - Shake, Jay G.
AU - Gruber, Peter J.
AU - Baumgartner, William A.
AU - Senechal, Guylaine
AU - Meyers, Jennifer
AU - Redmond, J. Mark
AU - Pittenger, Mark F.
AU - Martin, Bradley J.
N1 - Funding Information:
Osiris Therapeutics, Inc, received a research award from the Department of Commerce, National Institute of Standards and Technology/Advanced Technologies Program (NIST/ATP). The Cardiac Surgery Laboratory is partially funded by generous gifts from the Mildred and Carmont Blitz Cardiac Research Fund. JGS is currently the Irene Piccinini Investigator in Cardiac Surgery established to recognize outstanding research trainees in Cardiac Surgery at The Johns Hopkins Medical Institutions. The authors would like to thank the scientists at Osiris for their contributions and continued enthusiasm. Also, they wish to thank Mr Jeffrey Brawn and Ms Melissa Haggerty for their outstanding technical assistance. This project could not have been completed without the participation of all of them.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0036266426&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036266426&partnerID=8YFLogxK
U2 - 10.1016/S0003-4975(02)03517-8
DO - 10.1016/S0003-4975(02)03517-8
M3 - Article
C2 - 12078791
AN - SCOPUS:0036266426
SN - 0003-4975
VL - 73
SP - 1919
EP - 1926
JO - Annals of Thoracic Surgery
JF - Annals of Thoracic Surgery
IS - 6
ER -