PMID- 24152766
OWN - NLM
STAT- MEDLINE
DCOM- 20151116
LR  - 20150224
IS  - 1555-3892 (Electronic)
IS  - 0963-6897 (Linking)
VI  - 24
IP  - 2
DP  - 2015
TI  - Enhanced recovery from chronic ischemic injury by bone marrow cells in a rat 
      model of ischemic stroke.
PG  - 167-82
LID - 10.3727/096368913X674666 [doi]
AB  - Even after decades of intensive studies, therapeutic options for patients with 
      stroke are rather limited. Thrombolytic drugs effectively treat the very acute 
      stage of stroke, and several neuroprotectants that are designed to treat 
      secondary injury following stroke are being tested in clinical trials. However, 
      these pharmacological approaches primarily focus on acute stroke recovery, and 
      few options are available for treating chronic stroke patients. In recent years, 
      stem cell-mediated regenerative approaches have emerged as promising therapeutic 
      strategies for treating the chronic stage of stroke. In this study, we examined 
      whether systemically administered bone marrow cells (BMCs) could have beneficial 
      effects in a rat model of chronic ischemia. Our transplantation experiments using 
      BMCs obtained from ischemic donor rats showed functional and structural recovery 
      during the chronic stage of stroke. BMC-mediated neural proliferation was 
      prominent in the brains of rats with chronic stroke, and most of the new cells 
      eventually became neurons instead of astrocytes. BMC-mediated enhanced neural 
      proliferation coincided with a significant reduction ( approximately 50%) in the number of 
      activated microglia, which is consistent with previous reports of enhanced neural 
      proliferation being linked to microglial inactivation. Strikingly, approximately 
      57% of the BMCs that infiltrated the chronic ischemic brain were CD25(+) cells, 
      suggesting that these cells may exert the beneficial effects associated with BMC 
      transplantation. Based on the reported anti-inflammatory role of CD25(+) 
      regulatory T-cells in acute experimental stroke, we propose a working model 
      delineating the positive effects of BMC transplantation during the chronic phase 
      of stroke; infiltrating BMCs (mostly CD25(+) cells) reduce activated microglia, 
      which leads to enhanced neural proliferation and enhanced recovery from neuronal 
      damage in this rat model of chronic stroke. This study provides valuable insights 
      into the effect of BMC transplantation in the chronic ischemic brain, which may 
      lead to the development of effective therapy for chronic stroke patients who 
      currently lack satisfactory therapeutic options.
FAU - Yoo, Jongman
AU  - Yoo J
AD  - Department of Biomedical Science, College of Life Science, CHA University, 
      Gyeonggido, Korea.
FAU - Seo, Jin-Ju
AU  - Seo JJ
FAU - Eom, Jang-Hyeon
AU  - Eom JH
FAU - Hwang, Dong-Youn
AU  - Hwang DY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131022
PL  - United States
TA  - Cell Transplant
JT  - Cell transplantation
JID - 9208854
RN  - 0 (Interleukin-2 Receptor alpha Subunit)
RN  - FYY3R43WGO (Minocycline)
SB  - IM
MH  - Animals
MH  - Behavior, Animal
MH  - Bone Marrow Cells/*cytology/metabolism
MH  - *Bone Marrow Transplantation
MH  - Brain/pathology
MH  - Brain Ischemia/pathology/*therapy
MH  - Cell Differentiation
MH  - Cell Proliferation/drug effects
MH  - Disease Models, Animal
MH  - Immunophenotyping
MH  - Interleukin-2 Receptor alpha Subunit/metabolism
MH  - Male
MH  - Microglia/metabolism
MH  - Minocycline/pharmacology
MH  - Neurons/cytology/drug effects/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Recovery of Function
MH  - T-Lymphocytes, Regulatory/cytology/immunology/metabolism
MH  - Transplantation, Homologous
EDAT- 2013/10/25 06:00
MHDA- 2015/11/17 06:00
CRDT- 2013/10/25 06:00
PHST- 2013/10/25 06:00 [entrez]
PHST- 2013/10/25 06:00 [pubmed]
PHST- 2015/11/17 06:00 [medline]
AID - content-ct1119Yoo [pii]
AID - 10.3727/096368913X674666 [doi]
PST - ppublish
SO  - Cell Transplant. 2015;24(2):167-82. doi: 10.3727/096368913X674666. Epub 2013 Oct 
      22.