Adverse effects of bone marrow stromal cell treatment of stroke in diabetic rats.
Adverse effects of bone marrow stromal cell treatment of stroke in diabetic rats.
复制标题
糖尿病大鼠中风的骨髓基质细胞治疗的不良影响。
DOI：
10.1161/strokeaha.111.627174
复制
发表时间：
2011-12
期刊：
影响因子：
8.3
通讯作者：
Chopp M
中科院分区：
文献类型：
--
作者：
Chen J;Ye X;Yan T;Zhang C;Yang XP;Cui X;Cui Y;Zacharek A;Roberts C;Liu X;Dai X;Lu M;Chopp M
骨髓基质细胞（BMSCs）细胞治疗可改善非糖尿病大鼠中风后的功能恢复。然而，它对糖尿病合并中风的影响尚不清楚。本研究探讨骨髓间充质干细胞对1型糖尿病（T1DM）大鼠脑卒中转归的影响。用链脲佐菌素诱导成年雄性Wistar大鼠T1DM。非糖尿病和T1DM大鼠进行2小时的大脑中动脉闭塞（MCAO），在MCAO后24小时用或不用骨髓间充质干细胞治疗（3×106），并监测14天。与相应的T1DM-MCAO对照相比，BMSC大鼠治疗T1DM-MCAO未发现功能益处。T1DM-MCAO大鼠的BMSC治疗增加了死亡率、血脑屏障渗漏、脑出血和血管生成。与T1DM-MCAO对照相比，T1DM-MCAO+BMSCs大鼠颈内动脉内膜形成和脑小动脉狭窄/闭塞（P<0.05），而非糖尿病性脑卒中大鼠无此现象。我们进一步研究了bmsc诱导的T1DM-MCAO大鼠血脑屏障渗漏和血管损伤加速的潜在机制。我们发现，与未治疗的T1DM-MCAO+BMSC大鼠相比，缺血脑和颈内动脉血管生成素（一种血管生成因子）和ED1（巨噬细胞标志物）的表达在T1DM-MCAO+BMSC大鼠中显著增加，但在非糖尿病性卒中大鼠中没有。BMSC治疗对T1DM-MCAO大鼠的功能结果没有改善。相反，它增加了血脑屏障渗漏和大脑动脉内膜形成，动脉硬化，这可能是由于血管生成素的表达增加。因此，MCAO后24小时开始BMSC治疗可能对糖尿病卒中患者没有益处。
Cell therapy with bone marrow stromal cells (BMSCs) improves functional recovery after stroke in nondiabetic rats. However, its effect on diabetics with stroke is unknown. This study investigated the effect of BMSCs on stroke outcome in Type 1 diabetic (T1DM) rats. T1DM was induced in adult male Wistar rats by injecting streptozotocin. Nondiabetic and T1DM rats were subjected to 2 hours of middle cerebral artery occlusion (MCAO), treated with or without BMSCs (3×106) at 24 hours after MCAO, and monitored for 14 days. Functional benefit was not detected in T1DM-MCAO treated with BMSC rats compared with corresponding T1DM-MCAO controls. BMSC treatment in T1DM-MCAO rats had increased mortality, blood–brain barrier leakage, brain hemorrhage, and angiogenesis. Internal carotid artery neointimal formation and cerebral arteriole narrowing/occlusion were also observed in T1DM-MCAO+BMSCs rats compared with T1DM-MCAO controls (P<0.05), but not in nondiabetic stroke rats. We further studied the underlying mechanisms responsible for BMSC-induced blood–brain barrier leakage and accelerated vascular damage in T1DM-MCAO rats. We found that the expression of angiogenin (an angiogenic factor) and ED1 (a marker for macrophages) was significantly increased in the T1DM-MCAO+BMSC rats in the ischemic brain and internal carotid artery compared with nontreated T1DM-MCAO rats, but not in nondiabetic stroke rats. BMSC therapy in T1DM-MCAO rats does not improve functional outcome. On the contrary, it increases blood–brain barrier leakage and cerebral artery neointimal formation, and arteriosclerosis, which possibly is due to increased expression of angiogenin. Thus, BMSC treatment starting 24 hours after MCAO may not be beneficial for diabetic subjects with stroke.