Division of Cardiovascular Medicine, Department of Internal Medicine, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, 43210, USA.
Cardiovasc Res. 2012 Jan 1;93(1):89-99. doi: 10.1093/cvr/cvr277. Epub 2011 Oct 19.
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.
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.
The 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.
心肌梗死（MI）与存活心肌细胞的不可逆转损失有关。细胞治疗是替代丢失的心肌细胞并恢复心脏功能的一种潜在选择。然而，细胞治疗面临许多挑战，包括移植细胞在富含氧化剂且缺乏生存支持机制的梗死区域中的存活。本研究的目的是评估补充氧气对大鼠模型中细胞移植和功能恢复的影响。
通过冠状动脉 60 分钟闭塞，随后恢复血流，诱导大鼠发生 MI。从成年大鼠骨髓中分离出间充质干细胞（MSCs），并将其移植到 MI 区域。接受 MSC 移植的大鼠接受高压氧（HBO：100% O2，2 个大气压）治疗 90 分钟，每周 5 天，共 4 周。实验组为：MI（对照组）、Ox（MI + HBO）、MSC（MI + MSC）和 MSC + Ox（MI + MSC + HBO）。HBO 暴露（氧合）在 MI 诱导后 3 天开始。MI 诱导后 1 周进行 MSC 移植。超声心动图显示，与 MI 或 MSC 组相比，MSC + Ox 组的心脏功能恢复显著。氧合增加了梗死区域中 MSC 的植入和血管密度。梗死组织的分子分析显示，与 MI 组相比，MSC + Ox 组的 NOS3 表达增加了 4 倍。
结果表明，MI 后大鼠每天接受高氧循环（氧循环）暴露可改善干细胞植入、心脏功能，并增加 NOS3 表达。
