PMID- 27729575
OWN - NLM
STAT- MEDLINE
DCOM- 20170529
LR  - 20211204
IS  - 1524-4628 (Electronic)
IS  - 0039-2499 (Print)
IS  - 0039-2499 (Linking)
VI  - 47
IP  - 11
DP  - 2016 Nov
TI  - Neurorestorative Responses to Delayed Human Mesenchymal Stromal Cells Treatment 
      of Stroke in Type 2 Diabetic Rats.
PG  - 2850-2858
AB  - BACKGROUND AND PURPOSE: Comorbidity of diabetes mellitus and stroke results in 
      worse functional outcome, poor long-term recovery, and extensive vascular damage. 
      We investigated the neurorestorative effects and mechanisms of stroke treatment 
      with human bone marrow-derived mesenchymal stromal cells (hMSCs) in type 2 
      diabetes mellitus (T2DM) rats. METHODS: Adult male Wistar rats were induced with 
      T2DM, subjected to 2 hours of middle cerebral artery occlusion (MCAo) and treated 
      via tail-vein injection with (1) PBS (n=8) and (2) hMSCs (n=10; 5x10(6)) at 3 
      days after MCAo. RESULTS: In T2DM rats, hMSCs administered at 3 days after MCAo 
      significantly improves neurological function without affecting blood glucose, 
      infarct volume, and incidence of brain hemorrhage in comparison to T2DM-MCAo 
      PBS-treated rats. Delayed hMSC treatment of T2DM stroke significantly improves 
      blood-brain barrier integrity, increases vascular and arterial density and 
      cerebral vascular perfusion, and promotes neuroblast cell migration and white 
      matter remodeling as indicated by increased doublecortin, axon, myelin, and 
      neurofilament density, respectively. Delayed hMSC treatment significantly 
      increases platelet-derived growth factor expression in the ischemic brain, 
      decreases proinflammatory M1 macrophage and increases anti-inflammatory M2 
      macrophage compared to PBS-treated T2DM-MCAo rats. In vitro data show that hMSCs 
      increase subventricular zone explant cell migration and primary cortical neuron 
      neurite outgrowth, whereas inhibition of platelet-derived growth factor decreases 
      hMSC-induced subventricular zone cell migration and axonal outgrowth. 
      CONCLUSIONS: In T2DM stroke rats, delayed hMSC treatment significantly improves 
      neurological functional outcome and increases neurorestorative effects and M2 
      macrophage polarization. Increasing brain platelet-derived growth factor 
      expression may contribute to hMSC-induced neurorestoration.
CI  - (c) 2016 American Heart Association, Inc.
FAU - Yan, Tao
AU  - Yan T
AD  - From the Tianjin Neurological and Gerontology Institute, Department of Neurology 
      of Tianjin Medical University General Hospital, China (T.Y., J.C.); Department of 
      Neurology (T.Y., P.V., M.C., A.Z., R.N., C.R., Y.Z., J.C.) and Department of 
      Biostatistics and Research Epidemiology (M.L.), Henry Ford Hospital, Detroit, MI; 
      and Department of Physics, Oakland University, Rochester, MI (M.C.).
FAU - Venkat, Poornima
AU  - Venkat P
AD  - From the Tianjin Neurological and Gerontology Institute, Department of Neurology 
      of Tianjin Medical University General Hospital, China (T.Y., J.C.); Department of 
      Neurology (T.Y., P.V., M.C., A.Z., R.N., C.R., Y.Z., J.C.) and Department of 
      Biostatistics and Research Epidemiology (M.L.), Henry Ford Hospital, Detroit, MI; 
      and Department of Physics, Oakland University, Rochester, MI (M.C.).
FAU - Chopp, Michael
AU  - Chopp M
AD  - From the Tianjin Neurological and Gerontology Institute, Department of Neurology 
      of Tianjin Medical University General Hospital, China (T.Y., J.C.); Department of 
      Neurology (T.Y., P.V., M.C., A.Z., R.N., C.R., Y.Z., J.C.) and Department of 
      Biostatistics and Research Epidemiology (M.L.), Henry Ford Hospital, Detroit, MI; 
      and Department of Physics, Oakland University, Rochester, MI (M.C.).
FAU - Zacharek, Alex
AU  - Zacharek A
AD  - From the Tianjin Neurological and Gerontology Institute, Department of Neurology 
      of Tianjin Medical University General Hospital, China (T.Y., J.C.); Department of 
      Neurology (T.Y., P.V., M.C., A.Z., R.N., C.R., Y.Z., J.C.) and Department of 
      Biostatistics and Research Epidemiology (M.L.), Henry Ford Hospital, Detroit, MI; 
      and Department of Physics, Oakland University, Rochester, MI (M.C.).
FAU - Ning, Ruizhuo
AU  - Ning R
AD  - From the Tianjin Neurological and Gerontology Institute, Department of Neurology 
      of Tianjin Medical University General Hospital, China (T.Y., J.C.); Department of 
      Neurology (T.Y., P.V., M.C., A.Z., R.N., C.R., Y.Z., J.C.) and Department of 
      Biostatistics and Research Epidemiology (M.L.), Henry Ford Hospital, Detroit, MI; 
      and Department of Physics, Oakland University, Rochester, MI (M.C.).
FAU - Roberts, Cynthia
AU  - Roberts C
AD  - From the Tianjin Neurological and Gerontology Institute, Department of Neurology 
      of Tianjin Medical University General Hospital, China (T.Y., J.C.); Department of 
      Neurology (T.Y., P.V., M.C., A.Z., R.N., C.R., Y.Z., J.C.) and Department of 
      Biostatistics and Research Epidemiology (M.L.), Henry Ford Hospital, Detroit, MI; 
      and Department of Physics, Oakland University, Rochester, MI (M.C.).
FAU - Zhang, Yi
AU  - Zhang Y
AD  - From the Tianjin Neurological and Gerontology Institute, Department of Neurology 
      of Tianjin Medical University General Hospital, China (T.Y., J.C.); Department of 
      Neurology (T.Y., P.V., M.C., A.Z., R.N., C.R., Y.Z., J.C.) and Department of 
      Biostatistics and Research Epidemiology (M.L.), Henry Ford Hospital, Detroit, MI; 
      and Department of Physics, Oakland University, Rochester, MI (M.C.).
FAU - Lu, Mei
AU  - Lu M
AD  - From the Tianjin Neurological and Gerontology Institute, Department of Neurology 
      of Tianjin Medical University General Hospital, China (T.Y., J.C.); Department of 
      Neurology (T.Y., P.V., M.C., A.Z., R.N., C.R., Y.Z., J.C.) and Department of 
      Biostatistics and Research Epidemiology (M.L.), Henry Ford Hospital, Detroit, MI; 
      and Department of Physics, Oakland University, Rochester, MI (M.C.).
FAU - Chen, Jieli
AU  - Chen J
AD  - From the Tianjin Neurological and Gerontology Institute, Department of Neurology 
      of Tianjin Medical University General Hospital, China (T.Y., J.C.); Department of 
      Neurology (T.Y., P.V., M.C., A.Z., R.N., C.R., Y.Z., J.C.) and Department of 
      Biostatistics and Research Epidemiology (M.L.), Henry Ford Hospital, Detroit, MI; 
      and Department of Physics, Oakland University, Rochester, MI (M.C.). 
      jieli@neuro.hfh.edu.
LA  - eng
GR  - R01 NS099030/NS/NINDS NIH HHS/United States
GR  - R01 NS088656/NS/NINDS NIH HHS/United States
GR  - R41 NS080329/NS/NINDS NIH HHS/United States
GR  - R41 NS064708/NS/NINDS NIH HHS/United States
GR  - R01 NS083078/NS/NINDS NIH HHS/United States
PT  - Journal Article
DEP - 20161011
PL  - United States
TA  - Stroke
JT  - Stroke
JID - 0235266
SB  - IM
MH  - Animals
MH  - *Diabetes Mellitus, Type 2
MH  - Disease Models, Animal
MH  - Doublecortin Protein
MH  - Humans
MH  - Male
MH  - Mesenchymal Stem Cell Transplantation/*methods
MH  - Neovascularization, Physiologic
MH  - Rats
MH  - Rats, Wistar
MH  - Recovery of Function
MH  - Stroke/metabolism/pathology/physiopathology/*therapy
PMC - PMC5134897
MID - NIHMS818235
OTO - NOTNLM
OT  - diabetes mellitus, type 2
OT  - ischemia
OT  - mesenchymal stromal cells
OT  - platelet-derived growth factor
OT  - stroke
EDAT- 2016/10/26 06:00
MHDA- 2017/05/30 06:00
PMCR- 2017/11/01
CRDT- 2016/10/13 06:00
PHST- 2016/07/07 00:00 [received]
PHST- 2016/09/14 00:00 [accepted]
PHST- 2016/10/26 06:00 [pubmed]
PHST- 2017/05/30 06:00 [medline]
PHST- 2016/10/13 06:00 [entrez]
PHST- 2017/11/01 00:00 [pmc-release]
AID - STROKEAHA.116.014686 [pii]
AID - 10.1161/STROKEAHA.116.014686 [doi]
PST - ppublish
SO  - Stroke. 2016 Nov;47(11):2850-2858. doi: 10.1161/STROKEAHA.116.014686. Epub 2016 
      Oct 11.