Yao Mu, Dieterle Thomas, Hale Sharon L, Dow Joan S, Kedes Laurence H, Peterson Kirk L, Kloner Robert A
Heart Institute, Good Samaritan Hospital, 1225 Wilshire Boulevard, CA 90017, Los Angeles, USA.
J Mol Cell Cardiol. 2003 Jun;35(6):661-70. doi: 10.1016/s0022-2828(03)00098-1.
The purpose of this study was to determine the long-term outcome of fetal cell transplantation into myocardial infarction on left ventricular (LV) function and remodeling.
While neonatal cell transplantation improved function for acute myocardial infarction, long-term data on the effects of cell-transplant therapy using a more primitive cell on ventricular remodeling and function are needed.Methods. - Therefore, we injected 4 x 10(6) Fischer 344 fetal cardiac cells or medium into 1-week old infarcts in adult female Fischer rats to assess long-term outcome.
Ten months after transplantation histologic analysis showed that cell implants were readily visible within the infarct scar. Infarct wall thickness was greater in cell-treated at 0.69 +/- 0.05 mm (n = 11) vs. medium-treated hearts at 0.33 +/- 0.01 mm (n = 19; P = 0.0001). Postmortem LV volume was 0.41 +/- 0.04 ml in cell-treated vs. 0.51 +/- 0.03 ml in medium-treated hearts (P < 0.04). Ejection fraction assessed by LV angiography was 0.40 +/- 0.02 in cell-treated (n = 16) vs. 0.33 +/- 0.02 in medium-treated hearts (n = 24; P < 0.03) with trends towards smaller in vivo end-diastolic and end-systolic volumes in cell-treated vs. medium-treated hearts. Polymerase chain reaction analysis of the Sry gene of the Y chromosome was positive in four of five cell-treated and zero of five medium-treated hearts confirming viability of male cells in female donors.
Over the course of 10 months, fetal cardiac cell transplantation into infarcted hearts increased infarct wall thickness, reduced LV dilatation, and improved LV ejection fraction. Thus, fetal cell-transplant therapy mitigated the longer-term adverse effects of LV remodeling following a myocardial infarction.
本研究旨在确定将胎儿细胞移植到心肌梗死区域对左心室(LV)功能和重塑的长期影响。
虽然新生儿细胞移植可改善急性心肌梗死的功能,但仍需要关于使用更原始细胞进行细胞移植治疗对心室重塑和功能影响的长期数据。方法:因此,我们将4×10⁶个Fischer 344胎儿心脏细胞或培养基注入成年雌性Fischer大鼠1周龄的梗死区域,以评估长期结果。
移植后10个月,组织学分析显示梗死瘢痕内可见细胞植入物。细胞治疗组梗死壁厚度为0.69±0.05mm(n = 11),大于培养基治疗组的0.33±0.01mm(n = 19;P = 0.0001)。细胞治疗组死后左心室体积为0.41±0.04ml,而培养基治疗组为0.51±0.03ml(P < 0.04)。通过左心室血管造影评估的射血分数,细胞治疗组为0.40±0.02(n = 16),培养基治疗组为0.33±0.02(n = 24;P < 0.03),细胞治疗组与培养基治疗组相比,体内舒张末期和收缩末期体积有变小趋势。对Y染色体的Sry基因进行聚合酶链反应分析,在5个细胞治疗组心脏中有4个呈阳性,5个培养基治疗组心脏中均为阴性,证实了雌性供体中雄性细胞的存活。
在10个月的时间里,将胎儿心脏细胞移植到梗死心脏中可增加梗死壁厚度,减少左心室扩张,并改善左心室射血分数。因此,胎儿细胞移植治疗减轻了心肌梗死后左心室重塑的长期不良影响。