PMID- 32889008
OWN - NLM
STAT- MEDLINE
DCOM- 20210310
LR  - 20210310
IS  - 1090-2430 (Electronic)
IS  - 0014-4886 (Linking)
VI  - 334
DP  - 2020 Dec
TI  - Exosomes derived from bone marrow mesenchymal stem cells harvested from type two 
      diabetes rats promotes neurorestorative effects after stroke in type two diabetes 
      rats.
PG  - 113456
LID - S0014-4886(20)30287-9 [pii]
LID - 10.1016/j.expneurol.2020.113456 [doi]
AB  - BACKGROUND AND PURPOSE: Diabetes elevates the risk of stroke, promotes 
      inflammation, and exacerbates vascular and white matter damage post stroke, 
      thereby hindering long term functional recovery. Here, we investigated the 
      neurorestorative effects and the underlying therapeutic mechanisms of treatment 
      of stroke in type 2 diabetic rats (T2DM) using exosomes harvested from bone 
      marrow stromal cells obtained from T2DM rats (T2DM-MSC-Exo). METHODS: T2DM was 
      induced in adult male Wistar rats using a combination of high fat diet and 
      Streptozotocin. Rats were subjected to transient 2 h middle cerebral artery 
      occlusion (MCAo) and 3 days later randomized to one of the following treatment 
      groups: 1) phosphate-buffered-saline (PBS, i.v), 2) T2DM-MSC-Exo, (3 x 10(11), 
      i.v), 3) T2DM-MSC-Exo with miR-9 over expression (miR9+/+-T2DM-MSC-Exo, 
      3 x 10(11), i.v) or 4) MSC-Exo derived from normoglycemic rats (Nor-MSC-Exo) 
      (3 x 10(11), i.v). T2DM sham control group is included as reference. Rats were 
      sacrificed 28 days after MCAo. RESULTS: T2DM-MSC-Exo treatment does not alter 
      blood glucose, lipid levels, or lesion volume, but significantly improves 
      neurological function and attenuates post-stroke weight loss compared to PBS 
      treated as well as Nor-MSC-Exo treated T2DM-stroke rats. Compared to PBS 
      treatment, T2DM-MSC-Exo treatment of T2DM-stroke rats significantly 1) increases 
      tight junction protein ZO-1 and improves blood brain barrier (BBB) integrity; 2) 
      promotes white matter remodeling indicated by increased axon and myelin density, 
      and increases oligodendrocytes and oligodendrocyte progenitor cell numbers in the 
      ischemic border zone as well as increases primary cortical neuronal axonal 
      outgrowth; 3) decreases activated microglia, M1 macrophages, and inflammatory 
      factors MMP-9 (matrix mettaloproteinase-9) and MCP-1 (monocyte chemoattractant 
      protein-1) expression in the ischemic brain; and 4) decreases miR-9 expression in 
      serum, and increases miR-9 target ABCA1 (ATP-binding cassette transporter 1) and 
      IGFR1 (Insulin-like growth factor 1 receptor) expression in the brain. 
      MiR9+/+-T2DM-MSC-Exo treatment significantly increases serum miR-9 expression 
      compared to PBS treated and T2DM-MSC-Exo treated T2DM stroke rats. Treatment of 
      T2DM stroke with miR9+/+-T2DM-MSC-Exo fails to improve functional outcome and 
      attenuates T2DM-MSC-Exo treatment induced white matter remodeling and 
      anti-inflammatory effects in T2DM stroke rats. CONCLUSIONS: T2DM-MSC-Exo 
      treatment for stroke in T2DM rats promotes neurorestorative effects and improves 
      functional outcome. Down regulation of miR-9 expression and increasing its target 
      ABCA1 pathway may contribute partially to T2DM-MSC-Exo treatment induced white 
      matter remodeling and anti-inflammatory responses.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Venkat, Poornima
AU  - Venkat P
AD  - Neurology Research, Henry Ford Hospital, Detroit, MI 48202, USA. Electronic 
      address: pvenkat3@hfhs.org.
FAU - Zacharek, Alex
AU  - Zacharek A
AD  - Neurology Research, Henry Ford Hospital, Detroit, MI 48202, USA.
FAU - Landschoot-Ward, Julie
AU  - Landschoot-Ward J
AD  - Neurology Research, Henry Ford Hospital, Detroit, MI 48202, USA.
FAU - Wang, Fengjie
AU  - Wang F
AD  - Neurology Research, Henry Ford Hospital, Detroit, MI 48202, USA.
FAU - Culmone, Lauren
AU  - Culmone L
AD  - Neurology Research, Henry Ford Hospital, Detroit, MI 48202, USA.
FAU - Chen, Zhili
AU  - Chen Z
AD  - Neurology Research, Henry Ford Hospital, Detroit, MI 48202, USA.
FAU - Chopp, Michael
AU  - Chopp M
AD  - Neurology Research, Henry Ford Hospital, Detroit, MI 48202, USA; Department of 
      Physics, Oakland University, Rochester, MI 48309, USA.
FAU - Chen, Jieli
AU  - Chen J
AD  - Neurology Research, Henry Ford Hospital, Detroit, MI 48202, USA. Electronic 
      address: jchen4@hfhs.org.
LA  - eng
PT  - Journal Article
DEP - 20200902
PL  - United States
TA  - Exp Neurol
JT  - Experimental neurology
JID - 0370712
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Diabetes Mellitus, Experimental/metabolism/*therapy
MH  - Diabetes Mellitus, Type 2/metabolism/*therapy
MH  - Exosomes/*transplantation
MH  - Male
MH  - Mesenchymal Stem Cell Transplantation/*methods
MH  - Mesenchymal Stem Cells/metabolism
MH  - Random Allocation
MH  - Rats
MH  - Rats, Wistar
MH  - Recovery of Function/*physiology
MH  - Stroke/metabolism/*therapy
OTO - NOTNLM
OT  - Exosomes
OT  - Mesenchymal stromal cells
OT  - Neurorestoration
OT  - Stroke
OT  - T2DM
OT  - miR-9
EDAT- 2020/09/06 06:00
MHDA- 2021/03/11 06:00
CRDT- 2020/09/05 12:20
PHST- 2020/05/01 00:00 [received]
PHST- 2020/07/08 00:00 [revised]
PHST- 2020/08/30 00:00 [accepted]
PHST- 2020/09/06 06:00 [pubmed]
PHST- 2021/03/11 06:00 [medline]
PHST- 2020/09/05 12:20 [entrez]
AID - S0014-4886(20)30287-9 [pii]
AID - 10.1016/j.expneurol.2020.113456 [doi]
PST - ppublish
SO  - Exp Neurol. 2020 Dec;334:113456. doi: 10.1016/j.expneurol.2020.113456. Epub 2020 
      Sep 2.