Mesenchymal stem cell injection induces cardiac nerve sprouting and increased tenascin expression in a swine model of myocardial infarction

Hui Nam Pak, Mohammed Qayyum, Dave T. Kim, Akira Hamabe, Yasushi Miyauchi, Michael C. Lill, Malkar Frantzen, Kaname Takizawa, Lan Chen, Michael C. Fishbein, Behrooz G. Sharifi, Peng-Sheng Chen, Raj Makkar

Research output: Contribution to journalArticle

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Abstract

Introduction: Mesenchymal stem cell (MSC) transplantation is a promising technique to improve cardiac function. Whether MSC can increase cardiac nerve density and contribute to the improved cardiac function is unclear. Methods and Results: Anterior wall myocardial infarction was created in 16 swine. One month later, 6 swine were given MSC and fresh bone marrow (BM) into infarcted myocardium (MSC group). Four swine were given fresh BM only (BM group), and 6 swine were given culture media (MI-only group). The swine were sacrificed 95.8 ± 3.5 days after MI. Six normal swine were used as control. Immunocytochemical staining was performed using antibodies against growth-associated protein 43 (GAP43), tyrosine hydroxylase (TH), and three subtypes of tenascin (R, C, and X). Five fields per slide were counted for nerve density. The results show the following. (1) There were more GAP43-positive nerves in the MSC group than in the BM, MI-only, or Control group (P <0.0001). TH staining showed higher nerve densities in the MSC group than in the MI-only (P <0.01) or Control group (P <0.0001) in the atria. (2) There were more sympathetic (TH-positive) nerves in myocardium distant from infarct than in the peri-infarct area (P <0.05). (3) Optical intensity and color analyses showed significantly higher tenascin R and tenascin C expression in the MSC and BM groups than in the MI-only or Control group (P <0.01). Conclusion: MSC injected with BM into swine infarct results in overexpression of cardiac tenascin, increased the magnitude of cardiac nerve sprouting in both atria and ventricles, and increased the magnitude of atrial sympathetic hyperinnervation 2 months after injection.

Original languageEnglish (US)
Pages (from-to)841-848
Number of pages8
JournalJournal of Cardiovascular Electrophysiology
Volume14
Issue number8
DOIs
StatePublished - Aug 1 2003
Externally publishedYes

Fingerprint

Tenascin
Mesenchymal Stromal Cells
Swine
Myocardial Infarction
Bone Marrow
Injections
Tyrosine 3-Monooxygenase
GAP-43 Protein
Control Groups
Myocardium
Anterior Wall Myocardial Infarction
Mesenchymal Stem Cell Transplantation
Staining and Labeling
Culture Media
Color
Antibodies

Keywords

  • Arrhythmia
  • Arteriosclerosis
  • Growth substances
  • Remodeling
  • Sympathetic nervous system

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology

Cite this

Mesenchymal stem cell injection induces cardiac nerve sprouting and increased tenascin expression in a swine model of myocardial infarction. / Pak, Hui Nam; Qayyum, Mohammed; Kim, Dave T.; Hamabe, Akira; Miyauchi, Yasushi; Lill, Michael C.; Frantzen, Malkar; Takizawa, Kaname; Chen, Lan; Fishbein, Michael C.; Sharifi, Behrooz G.; Chen, Peng-Sheng; Makkar, Raj.

In: Journal of Cardiovascular Electrophysiology, Vol. 14, No. 8, 01.08.2003, p. 841-848.

Research output: Contribution to journalArticle

Pak, HN, Qayyum, M, Kim, DT, Hamabe, A, Miyauchi, Y, Lill, MC, Frantzen, M, Takizawa, K, Chen, L, Fishbein, MC, Sharifi, BG, Chen, P-S & Makkar, R 2003, 'Mesenchymal stem cell injection induces cardiac nerve sprouting and increased tenascin expression in a swine model of myocardial infarction', Journal of Cardiovascular Electrophysiology, vol. 14, no. 8, pp. 841-848. https://doi.org/10.1046/j.1540-8167.2003.03124.x
Pak, Hui Nam ; Qayyum, Mohammed ; Kim, Dave T. ; Hamabe, Akira ; Miyauchi, Yasushi ; Lill, Michael C. ; Frantzen, Malkar ; Takizawa, Kaname ; Chen, Lan ; Fishbein, Michael C. ; Sharifi, Behrooz G. ; Chen, Peng-Sheng ; Makkar, Raj. / Mesenchymal stem cell injection induces cardiac nerve sprouting and increased tenascin expression in a swine model of myocardial infarction. In: Journal of Cardiovascular Electrophysiology. 2003 ; Vol. 14, No. 8. pp. 841-848.
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abstract = "Introduction: Mesenchymal stem cell (MSC) transplantation is a promising technique to improve cardiac function. Whether MSC can increase cardiac nerve density and contribute to the improved cardiac function is unclear. Methods and Results: Anterior wall myocardial infarction was created in 16 swine. One month later, 6 swine were given MSC and fresh bone marrow (BM) into infarcted myocardium (MSC group). Four swine were given fresh BM only (BM group), and 6 swine were given culture media (MI-only group). The swine were sacrificed 95.8 ± 3.5 days after MI. Six normal swine were used as control. Immunocytochemical staining was performed using antibodies against growth-associated protein 43 (GAP43), tyrosine hydroxylase (TH), and three subtypes of tenascin (R, C, and X). Five fields per slide were counted for nerve density. The results show the following. (1) There were more GAP43-positive nerves in the MSC group than in the BM, MI-only, or Control group (P <0.0001). TH staining showed higher nerve densities in the MSC group than in the MI-only (P <0.01) or Control group (P <0.0001) in the atria. (2) There were more sympathetic (TH-positive) nerves in myocardium distant from infarct than in the peri-infarct area (P <0.05). (3) Optical intensity and color analyses showed significantly higher tenascin R and tenascin C expression in the MSC and BM groups than in the MI-only or Control group (P <0.01). Conclusion: MSC injected with BM into swine infarct results in overexpression of cardiac tenascin, increased the magnitude of cardiac nerve sprouting in both atria and ventricles, and increased the magnitude of atrial sympathetic hyperinnervation 2 months after injection.",
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T1 - Mesenchymal stem cell injection induces cardiac nerve sprouting and increased tenascin expression in a swine model of myocardial infarction

AU - Pak, Hui Nam

AU - Qayyum, Mohammed

AU - Kim, Dave T.

AU - Hamabe, Akira

AU - Miyauchi, Yasushi

AU - Lill, Michael C.

AU - Frantzen, Malkar

AU - Takizawa, Kaname

AU - Chen, Lan

AU - Fishbein, Michael C.

AU - Sharifi, Behrooz G.

AU - Chen, Peng-Sheng

AU - Makkar, Raj

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N2 - Introduction: Mesenchymal stem cell (MSC) transplantation is a promising technique to improve cardiac function. Whether MSC can increase cardiac nerve density and contribute to the improved cardiac function is unclear. Methods and Results: Anterior wall myocardial infarction was created in 16 swine. One month later, 6 swine were given MSC and fresh bone marrow (BM) into infarcted myocardium (MSC group). Four swine were given fresh BM only (BM group), and 6 swine were given culture media (MI-only group). The swine were sacrificed 95.8 ± 3.5 days after MI. Six normal swine were used as control. Immunocytochemical staining was performed using antibodies against growth-associated protein 43 (GAP43), tyrosine hydroxylase (TH), and three subtypes of tenascin (R, C, and X). Five fields per slide were counted for nerve density. The results show the following. (1) There were more GAP43-positive nerves in the MSC group than in the BM, MI-only, or Control group (P <0.0001). TH staining showed higher nerve densities in the MSC group than in the MI-only (P <0.01) or Control group (P <0.0001) in the atria. (2) There were more sympathetic (TH-positive) nerves in myocardium distant from infarct than in the peri-infarct area (P <0.05). (3) Optical intensity and color analyses showed significantly higher tenascin R and tenascin C expression in the MSC and BM groups than in the MI-only or Control group (P <0.01). Conclusion: MSC injected with BM into swine infarct results in overexpression of cardiac tenascin, increased the magnitude of cardiac nerve sprouting in both atria and ventricles, and increased the magnitude of atrial sympathetic hyperinnervation 2 months after injection.

AB - Introduction: Mesenchymal stem cell (MSC) transplantation is a promising technique to improve cardiac function. Whether MSC can increase cardiac nerve density and contribute to the improved cardiac function is unclear. Methods and Results: Anterior wall myocardial infarction was created in 16 swine. One month later, 6 swine were given MSC and fresh bone marrow (BM) into infarcted myocardium (MSC group). Four swine were given fresh BM only (BM group), and 6 swine were given culture media (MI-only group). The swine were sacrificed 95.8 ± 3.5 days after MI. Six normal swine were used as control. Immunocytochemical staining was performed using antibodies against growth-associated protein 43 (GAP43), tyrosine hydroxylase (TH), and three subtypes of tenascin (R, C, and X). Five fields per slide were counted for nerve density. The results show the following. (1) There were more GAP43-positive nerves in the MSC group than in the BM, MI-only, or Control group (P <0.0001). TH staining showed higher nerve densities in the MSC group than in the MI-only (P <0.01) or Control group (P <0.0001) in the atria. (2) There were more sympathetic (TH-positive) nerves in myocardium distant from infarct than in the peri-infarct area (P <0.05). (3) Optical intensity and color analyses showed significantly higher tenascin R and tenascin C expression in the MSC and BM groups than in the MI-only or Control group (P <0.01). Conclusion: MSC injected with BM into swine infarct results in overexpression of cardiac tenascin, increased the magnitude of cardiac nerve sprouting in both atria and ventricles, and increased the magnitude of atrial sympathetic hyperinnervation 2 months after injection.

KW - Arrhythmia

KW - Arteriosclerosis

KW - Growth substances

KW - Remodeling

KW - Sympathetic nervous system

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