干细胞治疗对心力衰竭中骨骼肌重构的贡献。

The contribution of stem cell therapy to skeletal muscle remodeling in heart failure.

机构信息

Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Padua, Italy.

出版信息

Int J Cardiol. 2013 Oct 3;168(3):2014-21. doi: 10.1016/j.ijcard.2013.01.168. Epub 2013 Feb 28.

DOI:10.1016/j.ijcard.2013.01.168

PMID:23453873

Abstract

BACKGROUND

The aim of our study was to investigate whether stem cell (SC) therapy with human amniotic fluid stem cells (hAFS, fetal stem cells) and rat adipose tissue stromal vascular fraction cells-GFP positive cells (rSVC-GFP) was able to produce favorable effects on skeletal muscle (SM) remodeling in a well-established rat model of right heart failure (RHF).

METHODS

RHF was induced by monocrotaline (MCT) in Sprague-Dawley rats. Three weeks later, four millions of hAFS or rSVC-GFP cells were injected via tail vein. SM remodeling was assessed by Soleus muscle fiber cross sectional area (CSA), myocyte apoptosis, myosin heavy chain (MHC) composition, satellite cells pattern, and SC immunohistochemistry.

RESULTS

hAFS and rSVC-GFP injection produced significant SC homing in Soleus (0.68 ± 1.0 and 0.67 ± 0.75% respectively), with a 50% differentiation toward smooth muscle and endothelial cells. Pro-inflammatory cytokines were down regulated to levels similar to those of controls. SC-treated (SCT) rats showed increased CSA (p<0.004 vs MCT) similarly to controls with a reshift toward the slow MHC1 isoform. Apoptosis was significantly decreased (11.12.± 8.8 cells/mm(3) hAFS and 13.1+7.6 rSVC-GFP) (p<0.001 vs MCT) and similar to controls (5.38 ± 3.0 cells/mm(3)). RHF rats showed a dramatic reduction of satellite cells(MCT 0.2 ± 0.06% Pax7 native vs controls 2.60 ± 2.46%, p<0.001), while SCT induced a repopulation of both native and SC derived satellite cells (p<0.005).

CONCLUSIONS

SC treatment led to SM remodeling with satellite cell repopulation, decreased atrophy and apoptosis. Modulation of the cytokine milieu might play a crucial pathophysiological role with a possible scenario for autologous transplantation of SC in pts with CHF myopathy.

摘要

背景

我们的研究目的是探讨人羊膜间充质干细胞（hAFS，胎儿干细胞）和大鼠脂肪组织基质血管部分细胞-GFP 阳性细胞（rSVC-GFP）的干细胞（SC）治疗是否能对右心衰竭（RHF）大鼠模型中的骨骼肌（SM）重塑产生有利影响。

方法

通过给予单环素来诱导 RHF，在 Sprague-Dawley 大鼠中。3 周后，通过尾静脉注射 400 万个 hAFS 或 rSVC-GFP 细胞。通过比目鱼肌纤维横截面积（CSA）、肌细胞凋亡、肌球蛋白重链（MHC）组成、卫星细胞模式和 SC 免疫组织化学来评估 SM 重塑。

结果

hAFS 和 rSVC-GFP 注射使比目鱼肌中的 SC 归巢显著（分别为 0.68±1.0%和 0.67±0.75%），其中 50%分化为平滑肌和内皮细胞。促炎细胞因子的水平下调至与对照组相似的水平。与对照组相似，接受 SC 治疗（SCT）的大鼠 CSA 增加（p<0.004 比 MCT），向慢 MHC1 同工型的转变。凋亡明显减少（11.12.±8.8 个细胞/mm3 hAFS 和 13.1+7.6 rSVC-GFP）（p<0.001 比 MCT），与对照组相似（5.38±3.0 个细胞/mm3）。RHF 大鼠的卫星细胞数量显著减少（MCT 0.2±0.06% Pax7 天然比对照组 2.60±2.46%，p<0.001），而 SCT 诱导了天然和 SC 衍生的卫星细胞的重新填充（p<0.005）。