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      Therapeutic Efficacy of Human Mesenchymal Stem Cells With Different Delivery Route and Dosages in Rat Models of Spinal Cord Injury

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          Abstract

          Recent studies have shown that the use of mesenchymal stem/stromal cells (MSCs) may be a promising strategy for treating spinal cord injury (SCI). This study aimed to explore the effectiveness of human umbilical cord-derived MSCs (hUC-MSCs) with different administration routes and dosages on SCI rats. Following T10-spinal cord contusion in Sprague-Dawley rats (N = 60), three different dosages of hUC-MSCs were intrathecally injected into rats (SCI-ITH) after 24 h. Intravenous injection of hUC-MSCs (SCI-i.v.) and methylprednisolone reagent (SCI-PC) were used as positive controls (N = 10/group). A SCI control group without treatment and a sham operation group were injected with Multiple Electrolyte Injection solution. The locomotor function was assessed by Basso Beattie Bresnahan (BBB) rating score, magnetic resonance imaging (MRI), histopathology, and immunofluorescence. ELISA was conducted to further analyze the nerve injury and inflammation in the rat SCI model. Following SCI, BBB scores were significantly lower in the SCI groups compared with the sham operation group, but all the treated groups showed the recovery of hind-limb motor function, and rats receiving the high-dose intrathecal injection of hUC-MSCs (SCI-ITH-H) showed improved outcomes compared with rats in hUC-MSCs i.v. and positive control groups. Magnetic resonance imaging revealed significant edema and spinal cord lesion in the SCI groups, and significant recovery was observed in the medium and high-dose hUC-MSCs ITH groups. Histopathological staining showed that the necrotic area in spinal cord tissue was significantly reduced in the hUC-MSCs ITH-H group, and the immunofluorescence staining confirmed the neuroprotection effect of hUC-MSCs infused on SCI rats. The increase of inflammatory cytokines was repressed in hUC-MSCs ITH-H group. Our results confirmed that hUC-MSC administered via intrathecal injection has dose-dependent neuroprotection effect in SCI rats.

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          A sensitive and reliable locomotor rating scale for open field testing in rats.

          D. Michele Basso, MICHAEL S. BEATTIE, JACQUELINE C. BRESNAHAN (1995)
          Behavioral assessment after spinal cord contusion has long focused on open field locomotion using modifications of a rating scale developed by Tarlov and Klinger (1954). However, on-going modifications by several groups have made interlaboratory comparison of locomotor outcome measures difficult. The purpose of the present study was to develop an efficient, expanded, and unambiguous locomotor rating scale to standardize locomotor outcome measures across laboratories. Adult rats (n = 85) were contused at T7-9 cord level with an electromagnetic or weight drop device. Locomotor behavior was evaluated before injury, on the first or second postoperative day, and then for up to 10 weeks. Scoring categories and attributes were identified, operationally defined, and ranked based on the observed sequence of locomotor recovery patterns. These categories formed the Basso, Beattie, Bresnahan (BBB) Locomotor Rating Scale. The data indicate that the BBB scale is a valid and predictive measure of locomotor recovery able to distinguish behavioral outcomes due to different injuries and to predict anatomical alterations at the lesion center. Interrater reliability tests indicate that examiners with widely varying behavioral testing experience can apply the scale consistently and obtain similar scores. The BBB Locomotor Rating Scale offers investigators a more discriminating measure of behavioral outcome to evaluate treatments after spinal cord injury.
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            Concise Review: Multifaceted Characterization of Human Mesenchymal Stem Cells for Use in Regenerative Medicine

            Rebekah Samsonraj, Michael Raghunath, Victor Nurcombe … (2017)
            Abstract Mesenchymal stem cells (MSC) hold great potential for regenerative medicine because of their ability for self‐renewal and differentiation into tissue‐specific cells such as osteoblasts, chondrocytes, and adipocytes. MSCs orchestrate tissue development, maintenance and repair, and are useful for musculoskeletal regenerative therapies to treat age‐related orthopedic degenerative diseases and other clinical conditions. Importantly, MSCs produce secretory factors that play critical roles in tissue repair that support both engraftment and trophic functions (autocrine and paracrine). The development of uniform protocols for both preparation and characterization of MSCs, including standardized functional assays for evaluation of their biological potential, are critical factors contributing to their clinical utility. Quality control and release criteria for MSCs should include cell surface markers, differentiation potential, and other essential cell parameters. For example, cell surface marker profiles (surfactome), bone‐forming capacities in ectopic and orthotopic models, as well as cell size and granularity, telomere length, senescence status, trophic factor secretion (secretome), and immunomodulation, should be thoroughly assessed to predict MSC utility for regenerative medicine. We propose that these and other functionalities of MSCs should be characterized prior to use in clinical applications as part of comprehensive and uniform guidelines and release criteria for their clinical‐grade production to achieve predictably favorable treatment outcomes for stem cell therapy. Stem Cells Translational Medicine 2017;6:2173–2185
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              Microenvironment Imbalance of Spinal Cord Injury

              BaoYou Fan, Zhijian Wei, Xue Yao … (2018)
              Spinal cord injury (SCI), for which there currently is no cure, is a heavy burden on patient physiology and psychology. The microenvironment of the injured spinal cord is complicated. According to our previous work and the advancements in SCI research, ‘microenvironment imbalance’ is the main cause of the poor regeneration and recovery of SCI. Microenvironment imbalance is defined as an increase in inhibitory factors and decrease in promoting factors for tissues, cells and molecules at different times and spaces. There are imbalance of hemorrhage and ischemia, glial scar formation, demyelination and re-myelination at the tissue’s level. The cellular level imbalance involves an imbalance in the differentiation of endogenous stem cells and the transformation phenotypes of microglia and macrophages. The molecular level includes an imbalance of neurotrophic factors and their pro-peptides, cytokines, and chemokines. The imbalanced microenvironment of the spinal cord impairs regeneration and functional recovery. This review will aid in the understanding of the pathological processes involved in and the development of comprehensive treatments for SCI.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Cell Transplant
                Journal ID (iso-abbrev): Cell Transplant
                Journal ID (publisher-id): CLL
                Journal ID (hwp): spcll
                Title: Cell Transplantation
                Publisher: SAGE Publications (Sage CA: Los Angeles, CA )
                ISSN (Print): 0963-6897
                ISSN (Electronic): 1555-3892
                Publication date (Electronic): 30 November 2022
                Publication date Collection: Jan-Dec 2022
                Volume: 31
                Electronic Location Identifier: 09636897221139734
                Affiliations
                [1 ]Stem Cell Biology and Regenerative Medicine Institution, Beijing Yi-Chuang Institute of Bio-Industry, Beijing, China
                [2 ]Department of Critical Care Medicine, Peking University Third Hospital, Beijing, China
                [3 ]State Key Laboratory of Drug Delivery and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin, China
                Author notes
                [*]Qinggang Ge, Department of Critical Care Medicine, Peking University Third Hospital, Beijing 100191, China. Email: qingganggelin@ 123456126.com
                [*]Yongjun Liu, Stem Cell Biology and Regenerative Medicine Institution, Beijing Yi-Chuang Institute of Bio-Industry, Beijing 100176, China. Email: Andyliuliu2001@ 123456aliyun.com
                [*]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-8474-7106
                Article
                Publisher ID: 10.1177_09636897221139734
                DOI: 10.1177/09636897221139734
                PMC ID: 9716590
                PubMed ID: 36448598
                SO-VID: 680b1c4f-085b-4f7c-ab75-f2fbdb756142
                Copyright © © The Author(s) 2022
                License:

                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
                Date received : 25 August 2021
                Date revision received : 29 September 2022
                Date accepted : 2 November 2022
                Categories
                Subject: Original Article
                Custom metadata
                cover-date January-December 2022
                typesetter ts1

                Keywords: spinal cord injury,mesenchymal stem cells (mscs),intrathecal injection,neuro-protection,hind limb locomotor function
                Data availability:
                Keywords: spinal cord injury, mesenchymal stem cells (mscs), intrathecal injection, neuro-protection, hind limb locomotor function

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