Schenke-Layland Katja, Strem Brian M, Jordan Maria C, Deemedio Michael T, Hedrick Marc H, Roos Kenneth P, Fraser John K, Maclellan W Robb
Cardiovascular Research Laboratory, Departments of Medicine and Physiology, David Geffen School of Medicine at the University of California-Los Angeles (UCLA), Los Angeles, California 90095-1760, USA.
J Surg Res. 2009 May 15;153(2):217-23. doi: 10.1016/j.jss.2008.03.019. Epub 2008 Apr 10.
Adipose tissue consists of mature adipocytes and a mononuclear cell fraction termed adipose tissue-derived cells (ADCs). Within these heterogeneous ADCs exists a mesenchymal stem cell-like cell population, termed adipose tissue-derived stem cells. An important clinical advantage of adipose tissue-derived stem cells over other mesenchymal stem cell populations is the fact that they can be isolated in real time in sufficient quantity, such that ex vivo expansion is not necessary to obtain clinically relevant numbers for various therapeutic applications.
The aim of this investigation was to evaluate the therapeutic potential of freshly isolated ADCs in treating rats acutely following myocardial infarction. Rats underwent 45 min of left anterior descending artery occlusion followed by reperfusion. Fifteen minutes post-myocardial infarction, saline or 5 x 10(6) ADCs from green fluorescent protein-expressing transgenic rats were injected into the chamber of the left ventricle. Left ventricular function and morphometry was followed with 2-D echocardiography for 12 wk, at which point hearts were harvested for histological analysis.
Twelve weeks following cell therapy, left ventricular end-diastolic dimension was less dilated while the ejection fraction and cardiac output of ADC-treated rats were significantly improved compared to control rats (P < 0.01). Despite this benefit, absolute engraftment rates were low. This paradox may be partially explained by ADC-induced increases in both capillary and arteriole densities.
These data confirm the therapeutic benefit of freshly isolated ADCs delivered post-MI and suggest a novel beneficial mechanism for ADCs through a potent proangiogenic effect.
脂肪组织由成熟脂肪细胞和称为脂肪组织衍生细胞（ADCs）的单核细胞部分组成。在这些异质性的ADCs中存在一种间充质干细胞样细胞群，称为脂肪组织衍生干细胞。脂肪组织衍生干细胞相对于其他间充质干细胞群的一个重要临床优势是，它们可以实时分离出足够的数量，因此对于各种治疗应用而言，无需进行体外扩增即可获得临床相关数量的细胞。
本研究的目的是评估新鲜分离的ADCs对急性心肌梗死后大鼠的治疗潜力。大鼠经历45分钟的左前降支动脉闭塞，随后进行再灌注。心肌梗死后15分钟，将生理盐水或来自绿色荧光蛋白表达转基因大鼠的5×10⁶个ADCs注入左心室腔。用二维超声心动图跟踪左心室功能和形态学变化12周，此时取出心脏进行组织学分析。
细胞治疗12周后，与对照大鼠相比，ADCs治疗大鼠的左心室舒张末期内径扩张程度较小，射血分数和心输出量显著改善（P<0.01）。尽管有此益处，但绝对植入率较低。这种矛盾现象可能部分由ADCs诱导的毛细血管和小动脉密度增加来解释。
这些数据证实了心肌梗死后给予新鲜分离的ADCs的治疗益处，并提示ADCs通过强大的促血管生成作用具有一种新的有益机制。
