PMID- 29776835
OWN - NLM
STAT- MEDLINE
DCOM- 20190913
LR  - 20211204
IS  - 1477-2566 (Electronic)
IS  - 1465-3249 (Linking)
VI  - 20
IP  - 6
DP  - 2018 Jun
TI  - The combination of mannitol and temozolomide increases the effectiveness of stem 
      cell treatment in a chronic stroke model.
PG  - 820-829
LID - S1465-3249(18)30508-5 [pii]
LID - 10.1016/j.jcyt.2018.04.004 [doi]
AB  - BACKGROUND: The blood-brain barrier (BBB) presents a significant challenge to the 
      therapeutic efficacy of stem cells in chronic stroke. Various methods have been 
      developed to increase BBB permeability, but these are associated with adverse 
      effects and are, therefore, not clinically applicable. We recently identified 
      that combination drug treatment of mannitol and temozolomide improved BBB 
      permeability in vitro. Here, we investigated whether this combination could 
      increase the effectiveness of stem cell treatment in an animal model of chronic 
      ischemic stroke. METHODS: Chronic stroke was induced in rats by middle cerebral 
      artery occlusion (MCAo). After then, rats were administered human umbilical 
      cord-derived mesenchymal stromal cells (hUC-MSCs) by intravenous injection with 
      or without combination drug treatment of mannitol and temozolomide. To evaluate 
      the therapeutic efficacy, behavioral and immunohistochemical tests were 
      performed, and the differences among control, stem cell only, combination drug 
      only and stem cell with combination drug treatment were analyzed. RESULTS: 
      Although no hUC-MSCs were detected in any group, treatment with stem cells and 
      combination drug of mannitol and temozolomide increased the intracerebral 
      delivery of hCD63-positive microvesicles compared with stem cell only treatment. 
      Furthermore, treatment with stem cells and drug combination ameliorated 
      behavioral deficits and increased bromodeoxyuridine-, doublecortin- and 
      Reca-1-positive cells in the perilesional area as compared with other groups. 
      DISCUSSION: The combination drug treatment of mannitol and temozolomide allowed 
      for the efficient delivery of hUC-MSC-derived microvesicles into the brain in a 
      chronic stroke rat model. This attenuated behavioral deficits, likely by 
      improving neural regeneration and angiogenesis. Thus, combination drug treatment 
      of mannitol and temozolomide could be a novel therapeutic option for patients 
      with chronic ischemic stroke.
CI  - Copyright (c) 2018 International Society for Cellular Therapy. All rights reserved.
FAU - Choi, Chunggab
AU  - Choi C
AD  - Department of Neurology, CHA Bundang Medical Center, CHA University, Seongnam, 
      Republic of Korea.
FAU - Kim, Hye Min
AU  - Kim HM
AD  - Department of Neurology, CHA Bundang Medical Center, CHA University, Seongnam, 
      Republic of Korea.
FAU - Shon, Jeeheun
AU  - Shon J
AD  - Department of Neurology, CHA Bundang Medical Center, CHA University, Seongnam, 
      Republic of Korea.
FAU - Park, Jiae
AU  - Park J
AD  - Department of Neurology, CHA Bundang Medical Center, CHA University, Seongnam, 
      Republic of Korea.
FAU - Kim, Hyeong-Taek
AU  - Kim HT
AD  - Department of Neurology, CHA Bundang Medical Center, CHA University, Seongnam, 
      Republic of Korea.
FAU - Kang, Suk Ho
AU  - Kang SH
AD  - Department of Obstetrics and Gynecology, CHA Bundang Medical Center, CHA 
      University, Seongnam, Republic of Korea.
FAU - Oh, Seung-Hun
AU  - Oh SH
AD  - Department of Neurology, CHA Bundang Medical Center, CHA University, Seongnam, 
      Republic of Korea.
FAU - Kim, Nam Keun
AU  - Kim NK
AD  - Institute for Clinical Research, CHA Bundang Medical Center, CHA University, 
      Seongnam, Republic of Korea.
FAU - Kim, Ok Joon
AU  - Kim OJ
AD  - Department of Neurology, CHA Bundang Medical Center, CHA University, Seongnam, 
      Republic of Korea; Institute for Clinical Research, CHA Bundang Medical Center, 
      CHA University, Seongnam, Republic of Korea. Electronic address: 
      okjun77@cha.ac.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Cytotherapy
JT  - Cytotherapy
JID - 100895309
RN  - 0 (Dcx protein, rat)
RN  - 0 (Doublecortin Protein)
RN  - 3OWL53L36A (Mannitol)
RN  - YF1K15M17Y (Temozolomide)
SB  - IM
MH  - Animals
MH  - Chronic Disease
MH  - Combined Modality Therapy
MH  - Cord Blood Stem Cell Transplantation/adverse effects/*methods
MH  - Disease Models, Animal
MH  - Doublecortin Protein
MH  - Drug Therapy, Combination/adverse effects
MH  - Infarction, Middle Cerebral Artery/complications/pathology/therapy
MH  - Male
MH  - Mannitol/*administration & dosage/adverse effects
MH  - Mesenchymal Stem Cell Transplantation/adverse effects/*methods
MH  - Mesenchymal Stem Cells/cytology/drug effects/physiology
MH  - Nerve Regeneration/drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Stroke/pathology/*therapy
MH  - Temozolomide/*administration & dosage/adverse effects
MH  - Treatment Outcome
OTO - NOTNLM
OT  - blood-brain barrier
OT  - chronic ischemic stroke
OT  - mannitol
OT  - mesenchymal stromal cell
OT  - temozolomide
OT  - umbilical cord
EDAT- 2018/05/20 06:00
MHDA- 2019/09/14 06:00
CRDT- 2018/05/20 06:00
PHST- 2018/01/31 00:00 [received]
PHST- 2018/04/19 00:00 [revised]
PHST- 2018/04/25 00:00 [accepted]
PHST- 2018/05/20 06:00 [pubmed]
PHST- 2019/09/14 06:00 [medline]
PHST- 2018/05/20 06:00 [entrez]
AID - S1465-3249(18)30508-5 [pii]
AID - 10.1016/j.jcyt.2018.04.004 [doi]
PST - ppublish
SO  - Cytotherapy. 2018 Jun;20(6):820-829. doi: 10.1016/j.jcyt.2018.04.004.