Khan Mahmood, Meduru Sarath, Mohan Iyyapu K, Kuppusamy M Lakshmi, Wisel Sheik, Kulkarni Aditi, Rivera Brian K, Hamlin Robert L, Kuppusamy Periannan
Davis Heart and Lung Research Institute, Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA.
J Mol Cell Cardiol. 2009 Aug;47(2):275-87. doi: 10.1016/j.yjmcc.2009.04.005. Epub 2009 Apr 17.
A major limitation to the application of stem-cell therapy to repair ischemic heart damage is the low survival of transplanted cells in the heart, possibly due to poor oxygenation. We hypothesized that hyperbaric oxygenation (HBO) can be used as an adjuvant treatment to augment stem-cell therapy. Therefore, the goal of this study was to evaluate the effect of HBO on the engraftment of rat bone marrow-derived mesenchymal stem cells (MSCs) transplanted in infarct rat hearts. Myocardial infarction (MI) was induced in Fisher-344 rats by permanently ligating the left-anterior-descending coronary artery. MSCs, labeled with fluorescent superparamagnetic iron oxide (SPIO) particles, were transplanted in the infarct and peri-infarct regions of the MI hearts. HBO (100% oxygen at 2 ATA for 90 min) was administered daily for 2 weeks. Four MI groups were used: untreated (MI); HBO; MSC; MSC+HBO. Echocardiography, electro-vectorcardiography, and magnetic resonance imaging were used for functional evaluations. The engraftment of transplanted MSCs in the heart was confirmed by SPIO fluorescence and Prussian-blue staining. Immunohistochemical staining was used to identify key cellular and molecular markers including CD29, troponin-T, connexin-43, VEGF, alpha-smooth-muscle actin, and von Willebrand factor in the tissue. Compared to MI and MSC groups, the MSC+HBO group showed a significantly increased recovery of cardiac function including left-ventricular (LV) ejection fraction, fraction shortening, LV wall thickness, and QRS vector. Further, HBO treatment significantly increased the engraftment of CD29-positive cells, expression of connexin-43, troponin-T and VEGF, and angiogenesis in the infarct tissue. Thus, HBO appears to be a potential and clinically-viable adjuvant treatment for myocardial stem-cell therapy.
干细胞疗法应用于修复缺血性心脏损伤的一个主要限制是移植到心脏中的细胞存活率低，这可能是由于氧合不足所致。我们推测高压氧疗（HBO）可作为辅助治疗手段来增强干细胞疗法。因此，本研究的目的是评估HBO对移植到梗死大鼠心脏中的大鼠骨髓间充质干细胞（MSCs）植入的影响。通过永久性结扎左前降支冠状动脉在Fisher-344大鼠中诱导心肌梗死（MI）。将标记有荧光超顺磁性氧化铁（SPIO）颗粒的MSCs移植到MI心脏的梗死区和梗死周边区。每天给予HBO（2个绝对大气压下100%氧气，持续90分钟），共2周。使用了四个MI组：未治疗组（MI）；HBO组；MSCs组；MSCs+HBO组。使用超声心动图、心电向量图和磁共振成像进行功能评估。通过SPIO荧光和普鲁士蓝染色确认移植的MSCs在心脏中的植入。免疫组织化学染色用于鉴定组织中的关键细胞和分子标志物，包括CD29、肌钙蛋白-T、连接蛋白-43、血管内皮生长因子（VEGF）、α-平滑肌肌动蛋白和血管性血友病因子。与MI组和MSCs组相比，MSCs+HBO组的心脏功能恢复显著增加，包括左心室（LV）射血分数、缩短分数、LV壁厚度和QRS向量。此外，HBO治疗显著增加了梗死组织中CD29阳性细胞的植入、连接蛋白-43、肌钙蛋白-T和VEGF的表达以及血管生成。因此，HBO似乎是心肌干细胞治疗的一种潜在且具有临床可行性的辅助治疗方法。
