title: Early neuroprotective effect with lack of long-term cell replacement effect on experimental stroke after intra-arterial transplantation of adipose-derived mesenchymal stromal cells.
abstract: OBJECTIVE
  Adipose-derived mesenchymal stromal cells (AD-MSCs) have high proliferative capacity and ability to secrete trophic factors. Although intra-arterial (IA) transplantation of stem cells induces efficient engraftment to the host brain, it is unclear whether engrafted cells exert their long-term therapeutic effects through a bystander mechanism or a cell replacement mechanism.
  
  
  METHODS
  After induction of ischemia in rats by middle cerebral artery occlusion, we transplanted human AD-MSCs into their carotid arteries with the use of a micro-needle, and we then investigated the therapeutic effects during the early and late phases of ischemia by means of in vivo magnetic resonance imaging, functional and histological analyses.
  
  
  RESULTS
  During the early phase of cerebral ischemia, IA transplantation of AD-MSCs attenuated inflammation and enhanced endogenous neurogenesis. Transplanted animals showed a marked improvement in functional tests during the early phase of cerebral ischemia that was less prominent but still significant during the late phase of cerebral ischemia. Although the transplanted cells effectively migrated to the infarct area, only a small number of engrafted cells survived at 8 weeks after transplantation and differentiated into neuronal, glial and endothelial cells.
  
  
  CONCLUSIONS
  IA transplantation of human AD-MSCs provides an effective therapeutic modality in a rodent model of stroke, of which the main effects are mediated by a bystander mechanism at the early phase of ischemia.
authors.affiliation: Department of Neurology, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea.
authors.forename: Seung-Hun
authors.initials: SH
authors.lastname: Oh
authors.affiliation: Department of Biomedical Science and CHA Stem Cell Institute, College of Life Science, CHA University, Seongnam, Republic of Korea.
authors.forename: Chunggab
authors.initials: C
authors.lastname: Choi
authors.affiliation: Department of Biomedical Science and CHA Stem Cell Institute, College of Life Science, CHA University, Seongnam, Republic of Korea.
authors.forename: Da-Jeong
authors.initials: DJ
authors.lastname: Chang
authors.affiliation: Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Dong-Ah
authors.initials: DA
authors.lastname: Shin
authors.affiliation: Department of Biomedical Science and CHA Stem Cell Institute, College of Life Science, CHA University, Seongnam, Republic of Korea.
authors.forename: Nayeon
authors.initials: N
authors.lastname: Lee
authors.affiliation: Department of Biomedical Science and CHA Stem Cell Institute, College of Life Science, CHA University, Seongnam, Republic of Korea.
authors.forename: Iksoo
authors.initials: I
authors.lastname: Jeon
authors.affiliation: College of Pharmacy, Yonsei University, Incheon, Republic of Korea.
authors.forename: Jong-Hyuk
authors.initials: JH
authors.lastname: Sung
authors.affiliation: Division of Magnetic Resonance, Korea Basic Science Institute, Ochang, Republic of Korea.
authors.forename: Hyunseung
authors.initials: H
authors.lastname: Lee
authors.affiliation: Division of Magnetic Resonance, Korea Basic Science Institute, Ochang, Republic of Korea.
authors.forename: Kwan-Soo
authors.initials: KS
authors.lastname: Hong
authors.affiliation: Department of Biomedical Science and CHA Stem Cell Institute, College of Life Science, CHA University, Seongnam, Republic of Korea.
authors.forename: Jung Jae
authors.initials: JJ
authors.lastname: Ko
authors.affiliation: Department of Biomedical Science and CHA Stem Cell Institute, College of Life Science, CHA University, Seongnam, Republic of Korea. Electronic address: jsong@cha.ac.kr.
authors.forename: Jihwan
authors.initials: J
authors.lastname: Song
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000328:Adult; D000818:Animals; D002545:Brain Ischemia / Q000601:surgery*; D024201:Bystander Effect; D002454:Cell Differentiation; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000628:therapy*; D008279:Magnetic Resonance Imaging; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology; D055495:Neurogenesis / Q000502:physiology; D000066829:Neuroprotection / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000601:surgery*; D055815:Young Adult
keywords: adipose tissue; intra-arterial; mesenchymal stromal cells; neuroprotection; stroke; transplantation