title: Transplantation of Unique Subpopulation of Fibroblasts, Muse Cells, Ameliorates Experimental Stroke Possibly via Robust Neuronal Differentiation.
abstract: OBJECTIVE
  Muse cells reside as pre-existing pluripotent-like stem cells within the fibroblasts, are nontumorigenic, exhibit differentiation capacity into triploblastic-lineage cells, and replenish lost cells when transplanted in injury models. Cell fate and function of human skin fibroblast-derived Muse cells were evaluated in a rat stroke model.
  
  
  METHODS
  Muse cells (30,000), collected by pluripotent surface marker stage-specific embryonic antigen-3, were injected stereotaxically into three deposits within the rat ischemic cortex at 2 days after transient middle cerebral artery occlusion, and the cells' biological effects were examined for more than 84 days.
  
  
  RESULTS
  Muse cells spontaneously and promptly committed to neural/neuronal-lineage cells when cocultured with stroke brain slices. Muse-transplanted stroke rats exhibited significant improvements in neurological and motor functions compared to control groups at chronic days 70 and 84, without a reduction in the infarct size. Muse cells survived in the host brain for up to 84 days and differentiated into NeuN (∼ 65%), MAP-2 (∼ 32%), calbindin (∼ 28%), and GST-π (∼ 25%)-positive cells in the cortex, but glial fibrillary acidic protein-positive cells were rare. Tumor formation was not observed. Muse cells integrated into the sensory-motor cortex, extended their neurites into cervical spinal cord, and displayed normalized hind limb somatosensory evoked potentials.
  
  
  CONCLUSIONS
  Muse cells are unique from other stem cells in that they differentiate with high ratio into neuronal cells after integration with host brain microenvironment, possibly reconstructing the neuronal circuit to mitigate stroke symptoms. Human fibroblast-derived Muse cells pose as a novel source of transplantable stem cells, circumventing the need for gene manipulations, especially when contemplating autologous cell therapy for stroke.
authors.affiliation: Department of Stem Cell Biology and Histology.|Department of Neurosurgery.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Uchida
authors.affiliation: Department of Stem Cell Biology and Histology.|Department of Neurosurgery.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Morita
authors.affiliation: Department of Neurosurgery.
authors.forename: Kuniyasu
authors.initials: K
authors.lastname: Niizuma
authors.affiliation: Department of Anatomy and Anthropology.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kushida
authors.affiliation: Department of Anatomy and Anthropology.
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Kuroda
authors.affiliation: Department of Stem Cell Biology and Histology.
authors.forename: Shohei
authors.initials: S
authors.lastname: Wakao
authors.affiliation: Department of Neurosurgery.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sakata
authors.affiliation: Department of Physiology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Matsuzaka
authors.affiliation: Department of Physiology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Mushiake
authors.affiliation: Department of Neurosurgery.
authors.forename: Teiji
authors.initials: T
authors.lastname: Tominaga
authors.affiliation: Department of Neurosurgery and Brain Repair, University of South Florida College of Medicine, Tampa, Florida, USA.
authors.forename: Cesario V
authors.initials: CV
authors.lastname: Borlongan
authors.affiliation: Department of Stem Cell Biology and Histology.|Department of Anatomy and Anthropology.
authors.forename: Mari
authors.initials: M
authors.lastname: Dezawa
mesh_terms: D000328:Adult; D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000473:pathology; D002454:Cell Differentiation; D019070:Cell Lineage; D002470:Cell Survival; D060833:Cellular Microenvironment; D055724:Electrophysiological Phenomena; D005347:Fibroblasts / Q000166:cytology* / Q000637:transplantation*; D006801:Humans; D016513:Mice, SCID; D009044:Motor Cortex / Q000473:pathology; D009474:Neurons / Q000166:cytology*; D051381:Rats; D020521:Stroke / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*
keywords: Cellular therapy; Mesenchymal stem cells; Neuronal differentiation; Pluripotent stem cells; Transplantation