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      Progress in the Use of Induced Pluripotent Stem Cell‐Derived Neural Cells for Traumatic Spinal Cord Injuries in Animal Populations: Meta‐Analysis and Review

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          Abstract

          Induced pluripotent stem cells (iPSCs) are cells genetically reprogrammed from somatic cells, which can be differentiated into neurological lineages with the aim to replace or assist damaged neurons in the treatment of spinal cord injuries (SCIs) caused by physical trauma. Here, we review studies addressing the functional use of iPSC‐derived neural cells in SCIs and perform a meta‐analysis to determine if significant motor improvement is restored after treatment with iPSC‐derived neural cells compared with treatments using embryonic stem cell (ESC)‐derived counterpart cells and control treatments. Overall, based on locomotion scales in rodents and monkeys, our meta‐analysis indicates a therapeutic benefit for SCI treatment using neural cells derived from either iPSCs or ESCs, being this of importance due to existing ethical and immunological complications using ESCs. Results from these studies are evidence of the successes and limitations of iPSC‐derived neural cells in the recovery of motor capacity. stem cells translational medicine 2019;8:681&693

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          Adult SVZ stem cells lie in a vascular niche: a quantitative analysis of niche cell-cell interactions.

          Qin Shen, Yue Wang, Erzsebet Kokovay … (2008)
          There is an emerging understanding of the importance of the vascular system within stem cell niches. Here, we examine whether neural stem cells (NSCs) in the adult subventricular zone (SVZ) lie close to blood vessels, using three-dimensional whole mounts, confocal microscopy, and automated computer-based image quantification. We found that the SVZ contains a rich plexus of blood vessels that snake along and within neuroblast chains. Cells expressing stem cell markers, including GFAP, and proliferation markers are closely apposed to the laminin-containing extracellular matrix (ECM) surrounding vascular endothelial cells. Apical GFAP+ cells are admixed within the ependymal layer and some span between the ventricle and blood vessels, occupying a specialized microenvironment. Adult SVZ progenitor cells express the laminin receptor alpha6beta1 integrin, and blocking this inhibits their adhesion to endothelial cells, altering their position and proliferation in vivo, indicating that it plays a functional role in binding SVZ stem cells within the vascular niche.
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            Reprogramming of human primary somatic cells by OCT4 and chemical compounds.

            Saiyong Zhu, Wenlin Li, Hongyan Zhou … (2010)
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              Long-distance axonal growth from human induced pluripotent stem cells after spinal cord injury.

              Paul Lu, Grace Woodruff, Yaozhi Wang … (2014)
              Human induced pluripotent stem cells (iPSCs) from a healthy 86-year-old male were differentiated into neural stem cells and grafted into adult immunodeficient rats after spinal cord injury. Three months after C5 lateral hemisections, iPSCs survived and differentiated into neurons and glia and extended tens of thousands of axons from the lesion site over virtually the entire length of the rat CNS. These iPSC-derived axons extended through adult white matter of the injured spinal cord, frequently penetrating gray matter and forming synapses with rat neurons. In turn, host supraspinal motor axons penetrated human iPSC grafts and formed synapses. These findings indicate that intrinsic neuronal mechanisms readily overcome the inhibitory milieu of the adult injured spinal cord to extend many axons over very long distances; these capabilities persist even in neurons reprogrammed from very aged human cells.
              Article 0 comments Cited 141 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Luis G. Villa‐Diaz:
                ORCID: https://orcid.org/0000-0001-5709-9054
                luisvilladiaz@oakland.edu
                Journal
                Journal ID (nlm-ta): Stem Cells Transl Med
                Journal ID (iso-abbrev): Stem Cells Transl Med
                Journal ID (doi): 10.1002/(ISSN)2157-6580
                Journal ID (publisher-id): SCT3
                Title: Stem Cells Translational Medicine
                Publisher: John Wiley & Sons, Inc. (Hoboken, USA )
                ISSN (Print): 2157-6564
                ISSN (Electronic): 2157-6580
                Publication date (Electronic): 22 March 2019
                Publication date Collection: July 2019
                Volume: 8
                Issue: 7 ( doiID: 10.1002/sct3.2019.8.issue-7 )
                Pages: 681-693
                Affiliations
                [ 1 ] Honors College Oakland University Rochester Michigan USA
                [ 2 ] Department of Mathematics and Statistics Oakland University College of Arts and Sciences Rochester Michigan USA
                [ 3 ] Department of Biological Sciences Oakland University College of Arts and Sciences Rochester Michigan USA
                Author notes
                [*] [* ]Correspondence: Luis G. Villa‐Diaz, Ph.D., Department of Biological Sciences, Oakland University College of Arts and Sciences, Rochester, Michigan, USA. Telephone: 248‐370‐2837; e‐mail: luisvilladiaz@ 123456oakland.edu
                Author information
                https://orcid.org/0000-0001-5709-9054
                Article
                Publisher ID: SCT312486
                DOI: 10.1002/sctm.18-0225
                PMC ID: 6591555
                PubMed ID: 30903654
                SO-VID: 78a44740-38e6-43ab-b6a4-cca1886f18df
                Copyright © © 2019 The Authors. stem cells translational medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press
                License:

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                Date received : 10 October 2018
                Date accepted : 20 February 2019
                Page count
                Figures: 3, Tables: 5, Pages: 13, Words: 10495
                Funding
                Funded by: Biomedical Research Center of Oakland University
                Categories
                Subject: Tissue Engineering and Regenerative Medicine
                Subject: Tissue Engineering and Regenerative Medicine
                Custom metadata
                source-schema-version-number 2.0
                component-id sct312486
                cover-date July 2019
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_NLMPMC version:5.6.5 mode:remove_FC converted:25.06.2019

                Keywords: regenerative medicine,induced pluripotent stem cells,embryonic stem cells,spinal cord injury,meta‐analysis
                Data availability:
                Keywords: regenerative medicine, induced pluripotent stem cells, embryonic stem cells, spinal cord injury, meta‐analysis

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