title: Topical Therapy with Mesenchymal Stem Cells Following an Acute Experimental Head Injury Has Benefits in Motor-Behavioral Tests for Rodents.
abstract: The neuroprotective effects of mesenchymal stem cells (MSCs) have been reported in rodent and in preliminary clinical studies. MSCs are usually transplanted to patients by systemic infusion. However, only a few of the infused MSCs are delivered to the brain because of pulmonary trapping and the blood-brain barrier. In this study, MSCs were topically applied to the site of traumatic brain injury (TBI) and the neuroprotective effects were assessed.
  
  
  
  TBI was induced in Sprague-Dawley (SD) rats with an electromagnetically controlled cortical impact device after craniotomy was performed between the bregma and lambda, 1 mm lateral to the midline. We applied 1.5 million MSCs, derived from the adipose tissue of transgenic green fluorescent protein (GFP)-SD rats, to the exposed cerebral cortex at the injured site. The MSCs were held in position by a thin layer of fibrin. Neurological function in the test (n = 10) and control (n = 10) animals was evaluated using the rotarod test, the water maze test, and gait analysis at different time points.
  
  
  
  Within 5 days following topical application, GFP-positive cells were found in the brain parenchyma. These cells co-expressed with markers of Glial fibrillary acidic protein (GFAP), nestin, and NeuN. There was less neuronal death in CA1 and CA3 of the hippocampus in the test animals. Neurological functional recovery was significantly improved.
  
  
  
  Topically applied MSCs can migrate to the injured brain parenchyma and offer neuroprotective effects.
authors.affiliation: Division of Neurosurgery, Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China.|Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China.
authors.forename: P K
authors.initials: PK
authors.lastname: Lam
authors.affiliation: Department of Psychiatry and Neuroscience, Center of Neuroproteomics and Biomarkers Research, University of Florida, Gainesville, FL, USA.
authors.forename: Kevin K W
authors.initials: KK
authors.lastname: Wang
authors.affiliation: Chow Tai Fook-Cheng Yu Tung Surgical Stem cell Research Center, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China.
authors.forename: Anthony W I
authors.initials: AW
authors.lastname: Ip
authors.affiliation: Division of Neurosurgery, Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China.|Chow Tai Fook-Cheng Yu Tung Surgical Stem cell Research Center, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China.
authors.forename: Don W C
authors.initials: DW
authors.lastname: Ching
authors.affiliation: Division of Neurosurgery, Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China.|Chow Tai Fook-Cheng Yu Tung Surgical Stem cell Research Center, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China.
authors.forename: Cindy S W
authors.initials: CS
authors.lastname: Tong
authors.affiliation: Division of Neurosurgery, Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China.|Chow Tai Fook-Cheng Yu Tung Surgical Stem cell Research Center, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China.
authors.forename: Henry C H
authors.initials: HC
authors.lastname: Lau
authors.affiliation: Division of Neurosurgery, Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China.|Chow Tai Fook-Cheng Yu Tung Surgical Stem cell Research Center, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China.
authors.forename: Themis H C S
authors.initials: TH
authors.lastname: Kong
authors.affiliation: Division of Neurosurgery, Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China.
authors.forename: Paul B S
authors.initials: PB
authors.lastname: Lai
authors.affiliation: Division of Neurosurgery, Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China.
authors.forename: George K C
authors.initials: GK
authors.lastname: Wong
authors.affiliation: Division of Neurosurgery, Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China. wpoon@surgery.cuhk.edu.hk.
authors.forename: W S
authors.initials: WS
authors.lastname: Poon
mesh_terms: D000287:Administration, Topical; D000818:Animals; D030801:Animals, Genetically Modified; D034961:Antigens, Nuclear / Q000378:metabolism; D001522:Behavior, Animal; D001921:Brain / Q000166:cytology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000070642:Brain Injuries, Traumatic / Q000503:physiopathology / Q000628:therapy*; D056547:CA1 Region, Hippocampal / Q000473:pathology; D056654:CA3 Region, Hippocampal / Q000473:pathology; D004195:Disease Models, Animal; D005337:Fibrin / Q000627:therapeutic use; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D018782:Maze Learning; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D045442:Rotarod Performance Test
chemical_list: D034961:Antigens, Nuclear; C000614142:Gfap protein, rat; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; C546339:Rbfox3 protein, rat; D049452:Green Fluorescent Proteins; D005337:Fibrin
keywords: Mesenchymal stem cells; Topical application; Traumatic brain injury