当成肌细胞被早期移植时，其植入效果最佳：肝细胞生长因子的作用。

Engraftment is optimal when myoblasts are transplanted early: the role of hepatocyte growth factor.

机构信息

IWK Health Centre, Dalhousie University, Halifax, Nova Scotia, Canada.

出版信息

Ann Thorac Surg. 2010 Mar;89(3):829-35. doi: 10.1016/j.athoracsur.2009.12.007.

DOI:10.1016/j.athoracsur.2009.12.007

PMID:20172138

Abstract

BACKGROUND

In a recent clinical trial, skeletal myoblast (SKMB) transplantation performed late after myocardial infarction (MI) did not improve left ventricular function. We hypothesized that (1) delaying SKMB transplantation until a chronic infarct scar has developed reduces engraftment, and (2) hepatocyte growth factor (HGF), a main regulator of SKMBs, is present in acute but not chronic MI, potentially influencing engraftment.

METHODS

Rats underwent coronary artery ligation followed by SKMB transplantation immediately (n = 12) or delayed by 5 weeks (n = 11). The volume of engrafted SKMBs was quantified 6 weeks later. Hepatocyte growth factor was evaluated by computerized analysis of immunohistochemical labeling of rat heart sections 48 hours, 1 week, 2 weeks, and 5 weeks after coronary artery ligation. The impact of HGF on SKMB proliferation and its ability to protect against oxidative stress and hypoxia was evaluated in vitro.

RESULTS

Skeletal myoblast transplantation immediately after MI resulted in an engraftment volume of 29.1 +/- 2.9 mm(3). However, delaying SKMB transplantation 5 weeks caused a 95% drop in engraftment (1.4 +/- 0.3 mm(3); p < 0.001). Hepatocyte growth factor labeling in MIs 48 hours after coronary artery ligation was similar to control myocardium (18.0 +/- 2.0 versus 16.8 +/- 1.3 units). However, HGF declined progressively at 1, 2, and 5 weeks after MI (9.1 +/- 1.4, 4.2 +/- 0.4, and 3.1 +/- 0.6 units, respectively; p < 0.05 versus 48 hours). Hepatocyte growth factor caused a dose-dependent increase in SKMB proliferation in vitro and protected against oxidative stress and hypoxia.

CONCLUSIONS

These results demonstrate that engraftment of SKMBs is impaired when transplantation is delayed until a chronic infarct has developed. Hepatocyte growth factor in MI declines with time and may enhance engraftment of SKMBs transplanted early after MI. Delivery of exogenous HGF to enhance SKMB engraftment in chronic infarcts warrants further investigation.

摘要

背景

在最近的一项临床试验中，心肌梗死后（MI）晚期进行的骨骼肌母细胞（SKMB）移植并未改善左心室功能。我们假设：（1）延迟 SKMB 移植，直到慢性梗死瘢痕形成，会减少移植细胞的植入；（2）肝细胞生长因子（HGF）是 SKMB 的主要调节因子，在急性 MI 中存在，但在慢性 MI 中不存在，可能会影响植入。

方法

大鼠冠状动脉结扎后立即（n = 12）或延迟 5 周（n = 11）进行 SKMB 移植。6 周后定量检测移植 SKMB 的体积。通过计算机分析大鼠心脏切片的免疫组织化学标记，在冠状动脉结扎后 48 小时、1 周、2 周和 5 周评估 HGF 的含量。体外评估 HGF 对 SKMB 增殖的影响及其对氧化应激和缺氧的保护作用。

结果

MI 后立即进行 SKMB 移植可获得 29.1 ± 2.9 mm3 的植入体积。然而，延迟 5 周进行 SKMB 移植会导致植入量下降 95%（1.4 ± 0.3 mm3；p < 0.001）。冠状动脉结扎后 48 小时 MI 中的 HGF 标记与对照心肌相似（18.0 ± 2.0 与 16.8 ± 1.3 单位）。然而，HGF 在 MI 后 1、2 和 5 周时逐渐下降（分别为 9.1 ± 1.4、4.2 ± 0.4 和 3.1 ± 0.6 单位；p < 0.05 与 48 小时相比）。HGF 在体外呈剂量依赖性增加 SKMB 增殖，并能抵抗氧化应激和缺氧。