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      Stem Cell Therapy for Spinal Cord Injury

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          Abstract

          Traumatic spinal cord injury (SCI) results in direct and indirect damage to neural tissues, which results in motor and sensory dysfunction, dystonia, and pathological reflex that ultimately lead to paraplegia or tetraplegia. A loss of cells, axon regeneration failure, and time-sensitive pathophysiology make tissue repair difficult. Despite various medical developments, there are currently no effective regenerative treatments. Stem cell therapy is a promising treatment for SCI due to its multiple targets and reactivity benefits. The present review focuses on SCI stem cell therapy, including bone marrow mesenchymal stem cells, umbilical mesenchymal stem cells, adipose-derived mesenchymal stem cells, neural stem cells, neural progenitor cells, embryonic stem cells, induced pluripotent stem cells, and extracellular vesicles. Each cell type targets certain features of SCI pathology and shows therapeutic effects via cell replacement, nutritional support, scaffolds, and immunomodulation mechanisms. However, many preclinical studies and a growing number of clinical trials found that single-cell treatments had only limited benefits for SCI. SCI damage is multifaceted, and there is a growing consensus that a combined treatment is needed.

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          Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.

          Differentiated cells can be reprogrammed to an embryonic-like state by transfer of nuclear contents into oocytes or by fusion with embryonic stem (ES) cells. Little is known about factors that induce this reprogramming. Here, we demonstrate induction of pluripotent stem cells from mouse embryonic or adult fibroblasts by introducing four factors, Oct3/4, Sox2, c-Myc, and Klf4, under ES cell culture conditions. Unexpectedly, Nanog was dispensable. These cells, which we designated iPS (induced pluripotent stem) cells, exhibit the morphology and growth properties of ES cells and express ES cell marker genes. Subcutaneous transplantation of iPS cells into nude mice resulted in tumors containing a variety of tissues from all three germ layers. Following injection into blastocysts, iPS cells contributed to mouse embryonic development. These data demonstrate that pluripotent stem cells can be directly generated from fibroblast cultures by the addition of only a few defined factors.
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            Induction of pluripotent stem cells from adult human fibroblasts by defined factors.

            Successful reprogramming of differentiated human somatic cells into a pluripotent state would allow creation of patient- and disease-specific stem cells. We previously reported generation of induced pluripotent stem (iPS) cells, capable of germline transmission, from mouse somatic cells by transduction of four defined transcription factors. Here, we demonstrate the generation of iPS cells from adult human dermal fibroblasts with the same four factors: Oct3/4, Sox2, Klf4, and c-Myc. Human iPS cells were similar to human embryonic stem (ES) cells in morphology, proliferation, surface antigens, gene expression, epigenetic status of pluripotent cell-specific genes, and telomerase activity. Furthermore, these cells could differentiate into cell types of the three germ layers in vitro and in teratomas. These findings demonstrate that iPS cells can be generated from adult human fibroblasts.
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              Communication by Extracellular Vesicles: Where We Are and Where We Need to Go.

              In multicellular organisms, distant cells can exchange information by sending out signals composed of single molecules or, as increasingly exemplified in the literature, via complex packets stuffed with a selection of proteins, lipids, and nucleic acids, called extracellular vesicles (EVs; also known as exosomes and microvesicles, among other names). This Review covers some of the most striking functions described for EV secretion but also presents the limitations on our knowledge of their physiological roles. While there are initial indications that EV-mediated pathways operate in vivo, the actual nature of the EVs involved in these effects still needs to be clarified. Here, we focus on the context of tumor cells and their microenvironment, but similar results and challenges apply to all patho/physiological systems in which EV-mediated communication is proposed to take place.
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                Author and article information

                Journal
                Cell Transplant
                Cell Transplant
                CLL
                spcll
                Cell Transplantation
                SAGE Publications (Sage CA: Los Angeles, CA )
                0963-6897
                1555-3892
                9 February 2021
                Jan-Dec 2021
                : 30
                : 0963689721989266
                Affiliations
                [1 ]Department of Rehabilitation Medicine Center, Ringgold 34753, universityWest China Hospital/West China School of Medicine, Sichuan University; , Chengdu, Sichuan, PR China
                [2 ]Key Laboratory of Rehabilitation Medicine in Sichuan Province, Sichuan University, Chengdu, Sichuan Province, PR China
                [3 ]State Key Laboratory of Biotherapy, Ringgold 34753, universityWest China Hospital, Sichuan University; , Chengdu, Sichuan, China
                Author notes
                [*]Quan Wei, Department of Rehabilitation Medicine Center, West China Hospital/West China School of Medicine, Sichuan University, No. 37 Guoxuexiang, Chengdu, Sichuan Province, China. Email: weiquan@ 123456scu.edu.cn
                [*]

                These authors contributed equally to this article

                Author information
                https://orcid.org/0000-0001-7888-9186
                Article
                10.1177_0963689721989266
                10.1177/0963689721989266
                7876757
                33559479
                c4c0b6d7-8e53-410c-babc-4e84e70a2bc3
                © The Author(s) 2021

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 14 July 2020
                : 15 November 2020
                : 4 January 2021
                Categories
                Review
                Custom metadata
                January-December 2021
                ts3

                spinal cord injury,stem cells,bm-mscs,u-mscs,ad-mscs,nscs,npcs,escs,ipscs,evs
                spinal cord injury, stem cells, bm-mscs, u-mscs, ad-mscs, nscs, npcs, escs, ipscs, evs

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