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 language | English (US) |
|---|---|
| Pages (from-to) | 89-99 |
| Number of pages | 11 |
| Journal | Cardiovascular Research |
| Volume | 93 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2012 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Oxygen cycling in conjunction with stem cell transplantation induces NOS3 expression leading to attenuation of fibrosis and improved cardiac function
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
PY - 2012/1/1
Y1 - 2012/1/1
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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U2 - 10.1093/cvr/cvr277
DO - 10.1093/cvr/cvr277
M3 - Article
VL - 93
SP - 89
EP - 99
JO - Cardiovascular Research
JF - Cardiovascular Research
SN - 0008-6363
IS - 1
ER -