Recovery of neurological function of ischemic stroke by application of conditioned medium of bone marrow mesenchymal stem cells derived from normal and cerebral ischemia rats.
BACKGROUND
Several lines of evidence have demonstrated that bone marrow-derived mesenchymal stem cells (BM-MSC) release bioactive factors and provide neuroprotection for CNS injury. However, it remains elusive whether BM-MSC derived from healthy donors or stroke patients provides equal therapeutic potential. The present work aims to characterize BM-MSC prepared from normal healthy rats (NormBM-MSC) and cerebral ischemia rats (IschBM-MSC), and examine the effects of their conditioned medium (Cm) on ischemic stroke animal model.


RESULTS
Isolated NormBM-MSC or IschBM-MSC formed fibroblastic like morphology and expressed CD29, CD90 and CD44 but failed to express the hematopoietic marker CD34. The number of colony formation of BM-MSC was more abundant in IschBM-MSC than in NormBM-MSC. This is in contrast to the amount of Ficoll-fractionated mononuclear cells from normal donor and ischemic rats. The effect of cm of BM-MSC was further examined in cultures and in middle cerebral artery occlusion (MCAo) animal model. Both NormBM-MSC Cm and IschBM-MSC Cm effectively increased neuronal connection and survival in mixed neuron-glial cultures. In vivo, intravenous infusion of NormBM-MSC Cm and IschBM-MSC Cm after stroke onset remarkably improved functional recovery. Furthermore, NormBM-MSC Cm and IschBM-MSC Cm increased neurogenesis and attenuated microglia/ macrophage infiltration in MCAo rat brains.


CONCLUSIONS
Our data suggest equal effectiveness of BM-MSC Cm derived from ischemic animals or from a normal population. Our results thus revealed the potential of BM-MSC Cm on treatment of ischemic stroke.
May-Jywan
MJ
Tsai
Shen-Kou
SK
Tsai
Bo-Ruei
BR
Hu
Dann-Ying
DY
Liou
Shih-Ling
SL
Huang
Ming-Chao
MC
Huang
Wen-Cheng
WC
Huang
Neural Regeneration Laboratory, Center for Neural Regeneration, Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, No, 322, Section 2, Shih-Pai Road, Taipei City, Beitou District 112, Taiwan. hc_cheng@vghtpe.gov.tw.
Henrich
H
Cheng
Shiang-Suo
SS
Huang
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002545:Brain Ischemia / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D064987:Cell- and Tissue-Based Therapy; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051381:Rats; D020521:Stroke / Q000503:physiopathology / Q000628:therapy*
D017077:Culture Media, Conditioned