title: Engraftment of human mesenchymal stem cells in a rat photothrombotic cerebral infarction model : comparison of intra-arterial and intravenous infusion using MRI and histological analysis.
abstract: OBJECTIVE
  This study aimed to evaluate the hypotheses that administration routes [intra-arterial (IA) vs. intravenous (IV)] affect the early stage migration of transplanted human bone marrow-derived mesenchymal stem cells (hBM-MSCs) in acute brain infarction.
  
  
  METHODS
  Male Sprague-Dawley rats (n=40) were subjected to photothrombotic infarction. Three days after photothrombotic infarction, rats were randomly allocated to one of four experimental groups [IA group : n=12, IV group : n=12, superparamagnetic iron oxide (SPIO) group : n=8, control group : n=8]. All groups were subdivided into 1, 6, 24, and 48 hours groups according to time point of sacrifice. Magnetic resonance imaging (MRI) consisting of T2 weighted image (T2WI), T2(*) weighted image (T2(*)WI), susceptibility weighted image (SWI), and diffusion weighted image of rat brain were obtained prior to and at 1, 6, 24, and 48 hours post-implantation. After final MRI, rats were sacrificed and grafted cells were analyzed in brain and lung specimen using Prussian blue and immunohistochemical staining.
  
  
  RESULTS
  Grafted cells appeared as dark signal intensity regions at the peri-lesional zone. In IA group, dark signals in peri-lesional zone were more prominent compared with IV group. SWI showed largest dark signal followed by T2(*)WI and T2WI in both IA and IV groups. On Prussian blue staining, IA administration showed substantially increased migration and a large number of transplanted hBM-MSCs in the target brain than IV administration. The Prussian blue-positive cells were not detected in SPIO and control groups.
  
  
  CONCLUSIONS
  In a rat photothrombotic model of ischemic stroke, selective IA administration of human mesenchymal stem cells is more effective than IV administration. MRI and histological analyses revealed the time course of cell migration, and the numbers and distribution of hBM-MSCs delivered into the brain.
authors: Department of Radiology, Chung-Ang University College of Medicine, Seoul, Korea.
authors: Jun Soo
authors: JS
authors: Byun
authors: Department of Radiology, Chung-Ang University College of Medicine, Seoul, Korea.
authors: Byung Kook
authors: BK
authors: Kwak
authors: Department of Radiology, Chung-Ang University College of Medicine, Seoul, Korea.
authors: Jae Kyun
authors: JK
authors: Kim
authors: Department of Radiology, Chung-Ang University College of Medicine, Seoul, Korea.
authors: Jisung
authors: J
authors: Jung
authors: Department of Radiology, Chung-Ang University College of Medicine, Seoul, Korea.
authors: Bon Chul
authors: BC
authors: Ha
authors: Department of Radiology, Chung-Ang University College of Medicine, Seoul, Korea.
authors: Serah
authors: S
authors: Park
keywords: Intravascular; MRI; Mesenchymal stem cell; Photothrombotic cerebral infarction; Superparamagnetic iron oxide