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Brain & Heart                                       Human DPSCs attenuated amyotrophic lateral sclerosis in mice




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            Figure 4. Microglia in SOD1-G93A mice showed no evident significant changes after treatment with hDPSCs. (A) Immunofluorescence images depicting
            the amount of microglia in lumbosacral enlargement of the anterior horn of the spinal cord of WT and SOD1-G93A mice treated with vehicle or hDPSCs
            on day 150. Scale bar = 50 µm. (B) Histogram illustrating the relative proportions of microglia in WT and SOD1-G93A mice treated with vehicle or
            hDPSCs. n = 6 per group. (C) Flow cytometry analysis depicting the gating strategies used for microglia at day 150. (D) Histogram showing the percentage
            of CD45 intermediate CD11b  microglia (CD45 CD 11b+ ) in the brain of WT and SOD1-G93A mice treated with vehicle or hDPSCs on day 150. n = 4 in the WT
                                      int
                           +
            mice group, n = 6 in the vehicle-treated SOD1-G93A mice group, and n = 5 in the hDPSCs-treated SOD1-G93A mice group. (E) Histogram depicting the
            percentage of CD45 intermediate CD11b  microglia (CD45 CD11b ) in the spinal cord of WT and SOD1-G93A mice treated with vehicle or hDPSCs on day
                                                   +
                                              int
                                  +
            150. n = 4 in the WT mice group, n = 6 in vehicle-treated SOD1-G93A mice group, and n = 5 in the hDPSCs-treated SOD1-G93A mice group. Data were
            statistically analyzed using an unpaired t-test. Data were expressed as mean ± SEM. Notes: **p<0.01, ***p<0.001, and ****p<0.0001.
            Abbreviations: hDPSCs: Human dental pulp stem cells; WT: Wild type; SEM: Standard error of mean.
            the nanoscale plays a vital role in the differentiation   cord atrophy and conserving neurons, demonstrating the
            process of MSCs. 31,32  Furthermore, hDPSCs can secrete   beneficial effects of hDPSCs infusion in ALS mice. This
            some essential neurotrophic factors, including nerve   evidence based on murine models needs further validation
            growth factor proteins, BDNF, and glial cell line-derived   by  well-executed  randomized  controlled  clinical  trials.
            neurotrophic factor, which can nourish damaged neurons   Moreover, future optimized protocols for engineered
            and promote neural regeneration. 33-35  Previous findings   hDPSCs and the identification of reliable biomarkers to
            suggesting that hDPSCs play a potential regulatory role   predict therapeutic outcomes are essential steps toward the
            in the inflammatory response during disease progression   innovative use of hDPSCs for ALS treatment. Nevertheless,
            were contradicted by the findings of the present study, as   the use of hDPSCs as a therapeutic approach holds promise
            the population of microglia or astrocytes in SOD1-G93A   for future clinical interventions for patients with ALS.
            mice exhibited no significant changes after the infusion of
            hDPSCs.  Studies have reported that extracellular vesicles   Acknowledgments
                   36
            released by MSCs induce functional modifications in
            microglia. 37,38  Further investigation is required to clarify   The authors thank Beijing Chengnuo Medical Technology
            the impact of hDPSCs on glial cell features in ALS mice.   Co., Ltd. for providing the hDPSCs injection.
            Moreover, our study is limited by the fact that NeuN is   Funding
            not a specific marker for motor neurons. In addition, the
            mechanism through which hDPSCs infusion increases the   This work was supported in part by the National Science
            levels of trophic factors that reduce the clinical symptoms   Foundation of China (82122021).
            of ALS mice remains unknown.
                                                               Conflict of interest
            5. Conclusion                                      Wei-Na Jin is an Editorial Board Member of this journal

            The infusion of hDPSCs ameliorated clinical impairment   but was not in any way involved in the editorial and
            and prolonged the lifespan of ALS mice by retarding spinal   peer-review process conducted for this paper, directly or


            Volume 2 Issue 4 (2024)                         7                                doi: 10.36922/bh.3996
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