Center for Cardiovascular Research, James A Haley Hospital/University of South Florida, 13000 Bruce B. Downs Blvd, 111, Tampa, Florida 33612, FL, USA.
Regen Med. 2010 Jan;5(1):45-54. doi: 10.2217/rme.09.71.
We investigated whether human umbilical cord blood mononuclear cells (HUCBC) can limit progressive cardiomyopathy in TO2 hamsters.
MATERIALS & METHODS: A total of 22 TO2 1-month-old hamsters were treated with intramyocardial HUCBC, 4 x 10(6) in Isolyte, and 23 TO2 1-month-old hamsters were treated with intramyocardial Isolyte. A total of 16 1-month-old F1B hamsters served as controls and received intramyocardial Isolyte. Echocardiograms were performed on all hamsters prior to and monthly after treatment for 6 months. Heart tissues were then stained with hematoxylin and eosin, Masson's Trichrome and human leukocyte antibody.
In F1B hamsters, left ventricular fractional shortening (FS) and ejection fractions (EF) did not significantly decrease over 6 months. By contrast, in Isolyte-treated TO2 hamsters, FS decreased from 56.2 +/- 1.0% to 19.7 +/- 3.2% and EF decreased from 89.5 +/- 1.4% to 44.9 +/- 5.9% at 6 months (both p < 0.0001). The FS and EF in HUCBC-treated TO2 hamsters also progressively decreased over 6 months but the changes were more gradual, especially during the first month after HUCBC treatment when FS was 52.0 +/- 1.5% and EF was 89.5 +/- 1.4%, which was not significantly different from the FS and EF in the F1B hamsters. Moreover, in the HUCBC-treated hamsters, the FS and EF were 20-30% greater than FS and EF in Isolyte TO2 hamsters at 3 and 5 months (p < 0.01). In Isolyte-treated TO2 hamsters at 6-7 months, fibrosis involved 30.0 +/- 5.0% of left ventricle and 35.0 +/- 5.0% of septum. By contrast, in HUCBC-treated hamsters, fibrosis involved only 6.5 +/- 2.3% of the left ventricle and 6.3 +/- 1.8% of septum (p < 0.05). The average number of blood vessels per myocardial microscopic field in HUCBC-treated hearts was 53.5 +/- 0.8 versus 46.2 +/- 3.0 in Isolyte-treated TO2 hearts (p < 0.05).
HUCBC, when given as a single intramyocardial injection, can limit fibrosis and increase heart function over the short term in TO2 hamsters with cardiomyopathy.
我们旨在研究人脐带血单个核细胞(HUCBC)是否能限制 TO2 仓鼠进行性心肌病。
总共 22 只 1 个月大的 TO2 仓鼠接受了心肌内注射 HUCBC(Isolyte 中 4×106),23 只 1 个月大的 TO2 仓鼠接受了心肌内注射 Isolyte。总共 16 只 1 个月大的 F1B 仓鼠作为对照组,接受了心肌内注射 Isolyte。所有仓鼠在治疗前和治疗后 6 个月每月进行超声心动图检查。然后用苏木精和伊红、马松三色和人类白细胞抗体对心脏组织进行染色。
在 F1B 仓鼠中,左心室短轴缩短率(FS)和射血分数(EF)在 6 个月内没有显著下降。相比之下,在 Isolyte 处理的 TO2 仓鼠中,FS 从 56.2±1.0%降至 19.7±3.2%,EF 从 89.5±1.4%降至 44.9±5.9%(均 P<0.0001)。HUCBC 处理的 TO2 仓鼠的 FS 和 EF 在 6 个月内也逐渐下降,但变化更为渐进,尤其是在 HUCBC 治疗后第一个月,FS 为 52.0±1.5%,EF 为 89.5±1.4%,与 F1B 仓鼠的 FS 和 EF 无显著差异。此外,在 HUCBC 处理的仓鼠中,3 个月和 5 个月时,FS 和 EF 比 Isolyte TO2 仓鼠的 FS 和 EF 高 20-30%(P<0.01)。在 6-7 个月时,Isolyte 处理的 TO2 仓鼠的纤维化累及左心室的 30.0±5.0%和间隔的 35.0±5.0%。相比之下,在 HUCBC 处理的仓鼠中,纤维化仅累及左心室的 6.5±2.3%和间隔的 6.3±1.8%(P<0.05)。HUCBC 处理心脏的每个心肌镜下视野的平均血管数为 53.5±0.8 个,而 Isolyte 处理的 TO2 心脏为 46.2±3.0 个(P<0.05)。
单次心肌内注射 HUCBC 可在短期内限制 TO2 仓鼠心肌病的纤维化并增加心功能。