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      Rat hair follicle stem cells differentiate and promote recovery following spinal cord injury

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          Abstract

          Emerging studies of treating spinal cord injury (SCI) with adult stem cells led us to evaluate the effects of transplantation of hair follicle stem cells in rats with a compression-induced spinal cord lesion. Here, we proposed a hypothesis that rat hair follicle stem cell transplantation can promote the recovery of injured spinal cord. Compression-induced spinal cord injury was induced in Wistar rats in this study. The bulge area of the rat vibrissa follicles was isolated, cultivated and characterized with nestin as a stem cell marker. 5-Bromo-2′-deoxyuridine (BrdU) labeled bulge stem cells were transplanted into rats with spinal cord injury. Immunohistochemical staining results showed that some of the grafted cells could survive and differentiate into oligodendrocytes (receptor-interacting protein positive cells) and neuronal-like cells (βIII-tubulin positive cells) at 3 weeks after transplantation. In addition, recovery of hind limb locomotor function in spinal cord injury rats at 8 weeks following cell transplantation was assessed using the Basso, Beattie and Bresnahan (BBB) locomotor rating scale. The results demonstrate that the grafted hair follicle stem cells can survive for a long time period in vivo and differentiate into neuronal- and glial-like cells. These results suggest that hair follicle stem cells can promote the recovery of spinal cord injury.

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          Most cited references40

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          The biology of hair follicles.

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            Existence of slow-cycling limbal epithelial basal cells that can be preferentially stimulated to proliferate: implications on epithelial stem cells.

            Despite the obvious importance of epithelial stem cells in tissue homeostasis and tumorigenesis, little is known about their specific location or biological characteristics. Using 3H-thymidine labeling, we have identified a subpopulation of corneal epithelial basal cells, located in the peripheral cornea in a region called limbus, that are normally slow cycling, but can be stimulated to proliferate in response to wounding and to a tumor promotor, TPA. No such cells can be detected in the central corneal epithelium, suggesting that corneal epithelial stem cells are located in the limbus. A comparison of various types of epithelial stem cells revealed a common set of features, including their preferred location, pigment protection, and growth properties, which presumably play a crucial role in epithelial stem cell function.
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              Dynamics between stem cells, niche, and progeny in the hair follicle.

              Here, we exploit the hair follicle to define the point at which stem cells (SCs) become irreversibly committed along a differentiation lineage. Employing histone and nucleotide double-pulse-chase and lineage tracing, we show that the early SC descendents en route to becoming transit-amplifying cells retain stemness and slow-cycling properties and home back to the bulge niche when hair growth stops. These become the primary SCs for the next hair cycle, whereas initial bulge SCs become reserves for injury. Proliferating descendents further en route irreversibly lose their stemness, although they retain many SC markers and survive, unlike their transit-amplifying progeny. Remarkably, these progeny also home back to the bulge. Combining purification and gene expression analysis with differential ablation and functional experiments, we define critical functions for these non-SC niche residents and unveil the intriguing concept that an irreversibly committed cell in an SC lineage can become an essential contributor to the niche microenvironment. Copyright © 2011 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Neural Regen Res
                Neural Regen Res
                NRR
                Neural Regeneration Research
                Medknow Publications & Media Pvt Ltd (India )
                1673-5374
                1876-7958
                25 December 2013
                : 8
                : 36
                : 3365-3372
                Affiliations
                [1 ] Department of Anatomy and Pathology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
                [2 ] Department of Anatomical Sciences, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
                [3 ] Antimicrobial Resistance Research Center, Iran University of Medical Sciences, Tehran, Iran
                [4 ] Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran
                [5 ] Department of Anatomical Sciences, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
                [6 ] Neurophysiology Research Center, Urmia University of Medical Sciences, Urmia, Iran
                Author notes
                Corresponding author: Nowruz Najafzadeh, Assistant professor, Department of Anatomy and Pathology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran, n.najafzade@ 123456arums.ac.ir . (NY20120914001)

                Author contributions: Najafzadeh N was responsible for study conception and design, data collection, assembly, analysis and interpretation and paper writing. Nobakht M was in charge of study conception and design, data collection, assembly and interpretation. Pourheydar B participated in study conception and design, and data collection and assembly. Ghasem MG was also responsible for data collection and analysis and revised the paper. All authors

                Article
                NRR-8-3365
                10.3969/j.issn.1673-5374.2013.36.001
                4146002
                25206658
                b81de786-44a1-4bb8-873a-3c7da73ab80a
                Copyright: © Neural Regeneration Research

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 25 September 2013
                : 09 November 2013
                Categories
                Research and Report Article: Spinal Cord Injury and Neural Regeneration

                neural regeneration,spinal cord injury,cell transplantation,cell therapy,hair follicle stem cells,oligodendrocytes,nerve cells,glial cells,receptor-interacting protein,grants-supported paper,neuroregeneration

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