title: Adverse effects of bone marrow stromal cell treatment of stroke in diabetic rats.
abstract: OBJECTIVE
  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.
authors.affiliation: Henry Ford Hospital, E&R Building, 3091, Detroit, MI 48202, USA. jieli@neuro.hfh.edu
authors.forename: Jieli
authors.initials: J
authors.lastname: Chen
authors.forename: Xinchun
authors.initials: X
authors.lastname: Ye
authors.forename: Tao
authors.initials: T
authors.lastname: Yan
authors.forename: Chunling
authors.initials: C
authors.lastname: Zhang
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Yang
authors.forename: Xu
authors.initials: X
authors.lastname: Cui
authors.forename: Yishen
authors.initials: Y
authors.lastname: Cui
authors.forename: Alex
authors.initials: A
authors.lastname: Zacharek
authors.forename: Cynthia
authors.initials: C
authors.lastname: Roberts
authors.forename: Xinfeng
authors.initials: X
authors.lastname: Liu
authors.forename: Xiangguo
authors.initials: X
authors.lastname: Dai
authors.forename: Mei
authors.initials: M
authors.lastname: Lu
authors.forename: Michael
authors.initials: M
authors.lastname: Chopp
mesh_terms: D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000378:metabolism*; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000378:metabolism; D020300:Intracranial Hemorrhages / Q000209:etiology / Q000378:metabolism; D008297:Male; D009389:Neovascularization, Pathologic / Q000209:etiology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function; D020521:Stroke / Q000150:complications / Q000378:metabolism / Q000601:surgery*; D017154:Stromal Cells / Q000637:transplantation*