BACKGROUND AND PURPOSE: 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. METHODS: 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 (3×10(6)) at 24 hours after MCAO, and monitored for 14 days. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND AND PURPOSE: Cell therapy with bone marrow stromal cells (BMSCs) improves functional recovery after stroke in nondiabeticrats. 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. METHODS: 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 (3×10(6)) at 24 hours after MCAO, and monitored for 14 days. RESULTS: Functional benefit was not detected in T1DM-MCAO treated with BMSC rats compared with corresponding T1DM-MCAO controls. BMSC treatment in T1DM-MCAOrats 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 strokerats. We further studied the underlying mechanisms responsible for BMSC-induced blood-brain barrier leakage and accelerated vascular damage in T1DM-MCAOrats. 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-MCAOrats, but not in nondiabetic strokerats. CONCLUSIONS: BMSC therapy in T1DM-MCAOrats 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.
Authors: José Alvarez-Sabín; Carlos A Molina; Joan Montaner; Juan F Arenillas; Rafael Huertas; Marc Ribo; Agusti Codina; Manuel Quintana Journal: Stroke Date: 2003-04-03 Impact factor: 7.914
Authors: F Chiarelli; M Pomilio; A Mohn; S Tumini; A Verrotti; A Mezzetti; F Cipollone; M Wasniewska; G Morgese; A Spagnoli Journal: Eur J Clin Invest Date: 2002-02 Impact factor: 4.686
Authors: Cesario V Borlongan; Jeffrey G Lind; Ora Dillon-Carter; Guolong Yu; Martin Hadman; Charles Cheng; James Carroll; David C Hess Journal: Brain Res Date: 2004-06-04 Impact factor: 3.252
Authors: Weiguo Li; Rebecca Ward; John Paul Valenzuela; Guangkuo Dong; Susan C Fagan; Adviye Ergul Journal: Transl Stroke Res Date: 2017-03-01 Impact factor: 6.829