Magnetic Enhancement of Cell Retention, Engraftment, and Functional Benefit after Intracoronary Delivery of Cardiac-Derived Stem Cells in a Rat Model of Ischemia/Reperfusion
The efficiency of stem cell transplantation is limited by low cell retention. Intracoronary (IC) delivery is convenient and widely used but exhibits particularly low cell retention rates. We sought to improve IC cell retention by magnetic targeting. Rat cardiosphere-derived cells labeled with iron m...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2012-06-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.3727/096368911X627381 |
| _version_ | 1818142374836043776 |
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| author | Ke Cheng Ph.D. Konstantinos Malliaras Tao-Sheng Li Baiming Sun Christiane Houde Giselle Galang Jeremy Smith Noriko Matsushita Eduardo Marbán M.D., Ph.D. |
| author_facet | Ke Cheng Ph.D. Konstantinos Malliaras Tao-Sheng Li Baiming Sun Christiane Houde Giselle Galang Jeremy Smith Noriko Matsushita Eduardo Marbán M.D., Ph.D. |
| author_sort | Ke Cheng Ph.D. |
| collection | DOAJ |
| description | The efficiency of stem cell transplantation is limited by low cell retention. Intracoronary (IC) delivery is convenient and widely used but exhibits particularly low cell retention rates. We sought to improve IC cell retention by magnetic targeting. Rat cardiosphere-derived cells labeled with iron microspheres were injected into the left ventricular cavity of syngeneic rats during brief aortic clamping. Placement of a 1.3 Tesla magnet ~1 cm above the heart during and after cell injection enhanced cell retention at 24 h by 5.2–6.4-fold when 1, 3, or 5 × 10 5 cells were infused, without elevation of serum troponin I (sTnI) levels. Higher cell doses (1 or 2 × 10 6 cells) did raise sTnI levels, due to microvascular obstruction; in this range, magnetic enhancement did not improve cell retention. To assess efficacy, 5 × 10 5 iron-labeled, GFP-expressing cells were infused into rat hearts after 45 min ischemia/20 min reperfusion of the left anterior coronary artery, with and without a superimposed magnet. By quantitative PCR and optical imaging, magnetic targeting increased cardiac retention of transplanted cells at 24 h, and decreased migration into the lungs. The enhanced cell engraftment persisted for at least 3 weeks, at which time left ventricular remodeling was attenuated, and therapeutic benefit (ejection fraction) was higher, in the magnetic targeting group. Histology revealed more GFP + cardiomyocytes, Ki67 + cardiomyocytes and GFP - /ckit + cells, and fewer TUNEL + cells, in hearts from the magnetic targeting group. In a rat model of ischemia/reperfusion injury, magnetically enhanced intracoronary cell delivery is safe and improves cell therapy outcomes. |
| first_indexed | 2024-12-11T11:14:46Z |
| format | Article |
| id | doaj.art-a825ada88bf2427f8e95a47d49ee4800 |
| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-12-11T11:14:46Z |
| publishDate | 2012-06-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-a825ada88bf2427f8e95a47d49ee48002022-12-22T01:09:23ZengSAGE PublishingCell Transplantation0963-68971555-38922012-06-012110.3727/096368911X627381Magnetic Enhancement of Cell Retention, Engraftment, and Functional Benefit after Intracoronary Delivery of Cardiac-Derived Stem Cells in a Rat Model of Ischemia/ReperfusionKe Cheng Ph.D.0Konstantinos Malliaras1Tao-Sheng Li2Baiming Sun3Christiane Houde4Giselle Galang5Jeremy Smith6Noriko Matsushita7Eduardo Marbán M.D., Ph.D.8Cedars-Sinai Heart Institute, Los Angeles, CA, USACedars-Sinai Heart Institute, Los Angeles, CA, USADepartment of Stem Cell Biology, Nagasaki University Graduate School of Biomedical Science, Nagasaki, JapanCedars-Sinai Heart Institute, Los Angeles, CA, USACedars-Sinai Heart Institute, Los Angeles, CA, USACedars-Sinai Heart Institute, Los Angeles, CA, USACedars-Sinai Heart Institute, Los Angeles, CA, USACedars-Sinai Heart Institute, Los Angeles, CA, USACedars-Sinai Heart Institute, Los Angeles, CA, USAThe efficiency of stem cell transplantation is limited by low cell retention. Intracoronary (IC) delivery is convenient and widely used but exhibits particularly low cell retention rates. We sought to improve IC cell retention by magnetic targeting. Rat cardiosphere-derived cells labeled with iron microspheres were injected into the left ventricular cavity of syngeneic rats during brief aortic clamping. Placement of a 1.3 Tesla magnet ~1 cm above the heart during and after cell injection enhanced cell retention at 24 h by 5.2–6.4-fold when 1, 3, or 5 × 10 5 cells were infused, without elevation of serum troponin I (sTnI) levels. Higher cell doses (1 or 2 × 10 6 cells) did raise sTnI levels, due to microvascular obstruction; in this range, magnetic enhancement did not improve cell retention. To assess efficacy, 5 × 10 5 iron-labeled, GFP-expressing cells were infused into rat hearts after 45 min ischemia/20 min reperfusion of the left anterior coronary artery, with and without a superimposed magnet. By quantitative PCR and optical imaging, magnetic targeting increased cardiac retention of transplanted cells at 24 h, and decreased migration into the lungs. The enhanced cell engraftment persisted for at least 3 weeks, at which time left ventricular remodeling was attenuated, and therapeutic benefit (ejection fraction) was higher, in the magnetic targeting group. Histology revealed more GFP + cardiomyocytes, Ki67 + cardiomyocytes and GFP - /ckit + cells, and fewer TUNEL + cells, in hearts from the magnetic targeting group. In a rat model of ischemia/reperfusion injury, magnetically enhanced intracoronary cell delivery is safe and improves cell therapy outcomes.https://doi.org/10.3727/096368911X627381 |
| spellingShingle | Ke Cheng Ph.D. Konstantinos Malliaras Tao-Sheng Li Baiming Sun Christiane Houde Giselle Galang Jeremy Smith Noriko Matsushita Eduardo Marbán M.D., Ph.D. Magnetic Enhancement of Cell Retention, Engraftment, and Functional Benefit after Intracoronary Delivery of Cardiac-Derived Stem Cells in a Rat Model of Ischemia/Reperfusion Cell Transplantation |
| title | Magnetic Enhancement of Cell Retention, Engraftment, and Functional Benefit after Intracoronary Delivery of Cardiac-Derived Stem Cells in a Rat Model of Ischemia/Reperfusion |
| title_full | Magnetic Enhancement of Cell Retention, Engraftment, and Functional Benefit after Intracoronary Delivery of Cardiac-Derived Stem Cells in a Rat Model of Ischemia/Reperfusion |
| title_fullStr | Magnetic Enhancement of Cell Retention, Engraftment, and Functional Benefit after Intracoronary Delivery of Cardiac-Derived Stem Cells in a Rat Model of Ischemia/Reperfusion |
| title_full_unstemmed | Magnetic Enhancement of Cell Retention, Engraftment, and Functional Benefit after Intracoronary Delivery of Cardiac-Derived Stem Cells in a Rat Model of Ischemia/Reperfusion |
| title_short | Magnetic Enhancement of Cell Retention, Engraftment, and Functional Benefit after Intracoronary Delivery of Cardiac-Derived Stem Cells in a Rat Model of Ischemia/Reperfusion |
| title_sort | magnetic enhancement of cell retention engraftment and functional benefit after intracoronary delivery of cardiac derived stem cells in a rat model of ischemia reperfusion |
| url | https://doi.org/10.3727/096368911X627381 |
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