Oxygen cycling in conjunction with stem cell transplantation induces NOS3 expression leading to attenuation of fibrosis and improved cardiac function

Mahmood Khan, Sarath Meduru, Rajan Gogna, Esha Madan, Lucas Citro, Muthulakshmi L. Kuppusamy, Muzzammil Sayyid, Mahmoud Mostafa, Robert L. Hamlin, Periannan Kuppusamy

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Aims Myocardial infarction (MI) is associated with irreversible loss of viable cardiomyocytes. Cell therapy is a potential option to replace the lost cardiomyocytes and restore cardiac function. However, cell therapy is faced with a number of challenges, including survival of the transplanted cells in the infarct region, which is characterized by abundant levels of oxidants and lack of a pro-survival support mechanism. The goal of the present study was to evaluate the effect of supplemental oxygenation on cell engraftment and functional recovery in a rat model. Methods and Results MI was induced in rats by a 60-min occlusion of the coronary artery, followed by restoration of flow. Mesenchymal stem cells (MSCs), isolated from adult rat bone marrow, were transplanted in the MI region. Rats with transplanted MSCs were exposed to hyperbaric oxygen (HBO: 100 O 2, 2 atmospheres absolute) for 90 min, 5 days/week for 4 weeks. The experimental groups were: MI (control), Ox (MI HBO), MSC (MI MSC), and MSC Ox (MI MSC HBO). HBO exposure (oxygenation) was started 3 days after induction of MI. MSCs were transplanted 1 week after induction of MI. Echocardiography showed a significant recovery of cardiac function in the MSC Ox group, when compared with the MI or MSC group. Oxygenation increased the engraftment of MSCs and vascular density in the infarct region. Molecular analysis of infarct tissue showed a four-fold increase in NOS3 expression in the MSC Ox group compared with the MI group. Conclusion sThe results showed that post-MI exposure of rats to daily cycles of hyperoxygenation (oxygen cycling) improved stem cell engraftment, cardiac function, and increased NOS3 expression.

Original languageEnglish (US)
Pages (from-to)89-99
Number of pages11
JournalCardiovascular Research
Volume93
Issue number1
DOIs
StatePublished - Jan 1 2012
Externally publishedYes

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Stem Cell Transplantation
Mesenchymal Stromal Cells
Fibrosis
Myocardial Infarction
Oxygen
Cell- and Tissue-Based Therapy
Cardiac Myocytes
Recovery of Function
Atmosphere
Oxidants
Blood Vessels
Echocardiography
Cell Survival
Coronary Vessels
Stem Cells
Cell Count
Bone Marrow

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)
  • Physiology

Cite this

Oxygen cycling in conjunction with stem cell transplantation induces NOS3 expression leading to attenuation of fibrosis and improved cardiac function. / Khan, Mahmood; Meduru, Sarath; Gogna, Rajan; Madan, Esha; Citro, Lucas; Kuppusamy, Muthulakshmi L.; Sayyid, Muzzammil; Mostafa, Mahmoud; Hamlin, Robert L.; Kuppusamy, Periannan.

In: Cardiovascular Research, Vol. 93, No. 1, 01.01.2012, p. 89-99.

Research output: Contribution to journalArticle

Khan, M, Meduru, S, Gogna, R, Madan, E, Citro, L, Kuppusamy, ML, Sayyid, M, Mostafa, M, Hamlin, RL & Kuppusamy, P 2012, 'Oxygen cycling in conjunction with stem cell transplantation induces NOS3 expression leading to attenuation of fibrosis and improved cardiac function', Cardiovascular Research, vol. 93, no. 1, pp. 89-99. https://doi.org/10.1093/cvr/cvr277
Khan, Mahmood ; Meduru, Sarath ; Gogna, Rajan ; Madan, Esha ; Citro, Lucas ; Kuppusamy, Muthulakshmi L. ; Sayyid, Muzzammil ; Mostafa, Mahmoud ; Hamlin, Robert L. ; Kuppusamy, Periannan. / Oxygen cycling in conjunction with stem cell transplantation induces NOS3 expression leading to attenuation of fibrosis and improved cardiac function. In: Cardiovascular Research. 2012 ; Vol. 93, No. 1. pp. 89-99.
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abstract = "Aims Myocardial infarction (MI) is associated with irreversible loss of viable cardiomyocytes. Cell therapy is a potential option to replace the lost cardiomyocytes and restore cardiac function. However, cell therapy is faced with a number of challenges, including survival of the transplanted cells in the infarct region, which is characterized by abundant levels of oxidants and lack of a pro-survival support mechanism. The goal of the present study was to evaluate the effect of supplemental oxygenation on cell engraftment and functional recovery in a rat model. Methods and Results MI was induced in rats by a 60-min occlusion of the coronary artery, followed by restoration of flow. Mesenchymal stem cells (MSCs), isolated from adult rat bone marrow, were transplanted in the MI region. Rats with transplanted MSCs were exposed to hyperbaric oxygen (HBO: 100 O 2, 2 atmospheres absolute) for 90 min, 5 days/week for 4 weeks. The experimental groups were: MI (control), Ox (MI HBO), MSC (MI MSC), and MSC Ox (MI MSC HBO). HBO exposure (oxygenation) was started 3 days after induction of MI. MSCs were transplanted 1 week after induction of MI. Echocardiography showed a significant recovery of cardiac function in the MSC Ox group, when compared with the MI or MSC group. Oxygenation increased the engraftment of MSCs and vascular density in the infarct region. Molecular analysis of infarct tissue showed a four-fold increase in NOS3 expression in the MSC Ox group compared with the MI group. Conclusion sThe results showed that post-MI exposure of rats to daily cycles of hyperoxygenation (oxygen cycling) improved stem cell engraftment, cardiac function, and increased NOS3 expression.",
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AU - Khan, Mahmood

AU - Meduru, Sarath

AU - Gogna, Rajan

AU - Madan, Esha

AU - Citro, Lucas

AU - Kuppusamy, Muthulakshmi L.

AU - Sayyid, Muzzammil

AU - Mostafa, Mahmoud

AU - Hamlin, Robert L.

AU - Kuppusamy, Periannan

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N2 - Aims Myocardial infarction (MI) is associated with irreversible loss of viable cardiomyocytes. Cell therapy is a potential option to replace the lost cardiomyocytes and restore cardiac function. However, cell therapy is faced with a number of challenges, including survival of the transplanted cells in the infarct region, which is characterized by abundant levels of oxidants and lack of a pro-survival support mechanism. The goal of the present study was to evaluate the effect of supplemental oxygenation on cell engraftment and functional recovery in a rat model. Methods and Results MI was induced in rats by a 60-min occlusion of the coronary artery, followed by restoration of flow. Mesenchymal stem cells (MSCs), isolated from adult rat bone marrow, were transplanted in the MI region. Rats with transplanted MSCs were exposed to hyperbaric oxygen (HBO: 100 O 2, 2 atmospheres absolute) for 90 min, 5 days/week for 4 weeks. The experimental groups were: MI (control), Ox (MI HBO), MSC (MI MSC), and MSC Ox (MI MSC HBO). HBO exposure (oxygenation) was started 3 days after induction of MI. MSCs were transplanted 1 week after induction of MI. Echocardiography showed a significant recovery of cardiac function in the MSC Ox group, when compared with the MI or MSC group. Oxygenation increased the engraftment of MSCs and vascular density in the infarct region. Molecular analysis of infarct tissue showed a four-fold increase in NOS3 expression in the MSC Ox group compared with the MI group. Conclusion sThe results showed that post-MI exposure of rats to daily cycles of hyperoxygenation (oxygen cycling) improved stem cell engraftment, cardiac function, and increased NOS3 expression.

AB - Aims Myocardial infarction (MI) is associated with irreversible loss of viable cardiomyocytes. Cell therapy is a potential option to replace the lost cardiomyocytes and restore cardiac function. However, cell therapy is faced with a number of challenges, including survival of the transplanted cells in the infarct region, which is characterized by abundant levels of oxidants and lack of a pro-survival support mechanism. The goal of the present study was to evaluate the effect of supplemental oxygenation on cell engraftment and functional recovery in a rat model. Methods and Results MI was induced in rats by a 60-min occlusion of the coronary artery, followed by restoration of flow. Mesenchymal stem cells (MSCs), isolated from adult rat bone marrow, were transplanted in the MI region. Rats with transplanted MSCs were exposed to hyperbaric oxygen (HBO: 100 O 2, 2 atmospheres absolute) for 90 min, 5 days/week for 4 weeks. The experimental groups were: MI (control), Ox (MI HBO), MSC (MI MSC), and MSC Ox (MI MSC HBO). HBO exposure (oxygenation) was started 3 days after induction of MI. MSCs were transplanted 1 week after induction of MI. Echocardiography showed a significant recovery of cardiac function in the MSC Ox group, when compared with the MI or MSC group. Oxygenation increased the engraftment of MSCs and vascular density in the infarct region. Molecular analysis of infarct tissue showed a four-fold increase in NOS3 expression in the MSC Ox group compared with the MI group. Conclusion sThe results showed that post-MI exposure of rats to daily cycles of hyperoxygenation (oxygen cycling) improved stem cell engraftment, cardiac function, and increased NOS3 expression.

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