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- Volume 22, Issue 4, 2022
Current Gene Therapy - Volume 22, Issue 4, 2022
Volume 22, Issue 4, 2022
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New Hope for Intervertebral Disc Degeneration: Bone Marrow Mesenchymal Stem Cells and Exosomes Derived from Bone Marrow Mesenchymal Stem Cell Transplantation
Authors: Xiao-bo Zhang, Xiang-yi Chen, Jin Qi, Hai-yu Zhou, Xiao-bing Zhao, Yi-cun Hu, Rui-hao Zhang, De-chen Yu, Xi-dan Gao, Ke-ping Wang and Lin MaBone Marrow Mesenchymal Stem Cells (BMSCs), multidirectional cells with self-renewal capacity, can differentiate into many cell types and play essential roles in tissue healing and regenerative medicine. Cell experiments and in vivo research in animal models have shown that BMSCs can repair degenerative discs by promoting cell proliferation and expressing Extracellular Matrix (ECM) components, such as type II collagen and protein-polysaccharides. Delaying or reversing the Intervertebral Disc Degeneration (IDD) process at an etiological level may be an effective strategy. However, despite increasingly in-depth research, some deficiencies in cell transplantation timing and strategy remain, preventing the clinical application of cell transplantation. Exosomes exhibit the characteristics of the mother cells from which they are secreted and can inhibit Nucleus Pulposus Cell (NPC) apoptosis and delay IDD through intercellular communication. Furthermore, the use of exosomes effectively avoids problems associated with cell transplantation, such as immune rejection. This manuscript introduces almost all of the BMSCs and exosomes derived from BMSCs (BMSCs-Exos) described in the IDD literature. Many challenges regarding the use of cell transplantation and therapeutic exosome intervention for IDD remain to be overcome.
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CAR-NK Cells for Cancer Therapy: Molecular Redesign of the Innate Antineoplastic Response
More LessThe Chimeric Antigen Receptor (CAR) has arisen as a powerful synthetic biology-based technology with demonstrated versatility for implementation in T and NK cells. Despite CAR T cell successes in clinical trials, several challenges remain to be addressed regarding adverse events and long-term efficacy. NK cells present an attractive alternative with intrinsic advantages over T cells for treating solid and liquid tumors. Early preclinical and clinical trials suggest at least two major advantages: improved safety and an off-the-shelf application in patients due to its HLA independence. Due to the early stages of CAR NK translation to clinical trials, limited data is currently available. By analyzing these results, it seems that CAR NK cells could offer a reduced probability of Cytokine Release Syndrome (CRS) or Graft versus Host Disease (GvHD) in cancer patients, reducing safety concerns. Furthermore, NK cell therapy approaches may be boosted by combining it with immunological checkpoint inhibitors and by implementing genetic circuits to direct CAR-bearing cell behavior. This review provides a description of the CAR technology for modifying NK cells and the translation from preclinical studies to early clinical trials in this new field of immunotherapy.
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The Effects of Human Umbilical Cord Mesenchymal Stem Cell Transplantation on Female Fertility Restoration in Mice
Authors: Qiwei Liu, Junhui Zhang, Yong Tang, Yuanyuan Ma, Zhigang Xue and Jinjuan WangBackground: Female fertility refers to the capacity to produce oocytes and achieve fertilization and pregnancy, and it is impaired by age, disease, environment and social pressure. However, no effective therapy that restores female reproductive ability has been established. Mesenchymal Stromal Cells (MSCs) exhibit multilineage differentiation potential and have attracted considerable attention as a tool for restoring female fertility. Methods: This study used human umbilical cord-MSCs (Huc-MSCs) to restore fertility in aging female mice and mice with chemotherapy-induced damage through the rescue of ovarian function and reconstruction of the fallopian tubes and uterus. In our study, two mouse models were generated: aging mice (35 weeks of age) and mice with chemotherapy-induced damage. Results: The effect of MSCs on the ovaries, fallopian tubes and uterus was evaluated by analyzing gonadal hormone levels and by performing morphological and statistical analyses. The levels of estradiol (E2) and follicle-stimulating hormone (FSH) exhibited significant recovery after Huc-MSC transplantation in both aging mice and chemotherapy-treated mice. Huc-MSC treatment also increased the number of primordial, developing and preovulatory follicles in the ovaries of mice. Moreover, MSCs were shown to rescue the morphology of the fallopian tubes and uterus through mechanisms such as cilia regeneration in the fallopian tubes and reformation of glands and endometrial tissue in the uterus. Conclusion: Huc-MSCs may represent an effective treatment for restoring female fertility through recovery from chemotherapy-induced damage and rescue of female reproductive organs from the effects of aging.
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Exosomal MiR-29a in Cardiomyocytes Induced by Angiotensin II Regulates Cardiac Microvascular Endothelial Cell Proliferation, Migration and Angiogenesis by Targeting VEGFA
Authors: Guangzhao Li, Zhimei Qiu, Chaofu Li, Ranzun Zhao, Yu Zhang, Changyin Shen, Weiwei Liu, Xianping Long, Shaowei Zhuang, Yan Wang and Bei ShiBackground: Exosomes released from cardiomyocytes (CMs) potentially play an important role in angiogenesis through microRNA (miR) delivery. Studies have reported an important role for miR-29a in regulating angiogenesis and pathological myocardial hypertrophy. However, whether CMderived exosomal miR-29a is involved in regulating cardiac microvascular endothelial cell (CMEC) homeostasis during myocardial hypertrophy has not been determined. Methods: Angiotensin II (Ang II) was used to induce CM hypertrophy, and ultracentrifugation was then used to extract exosomes from a CM-conditioned medium. CMECs were cocultured with a conditioned medium in the presence or absence of exosomes derived from CMs (Nor-exos) or exosomes derived from angiotensin II-induced CMs (Ang II-exos). Moreover, a rescue experiment was performed using CMs or CMECs infected with miR-29a mimics or inhibitors. Tube formation assays, Transwell assays, and 5-ethynyl-20-deoxyuridine (EdU) assays were then performed to determine the changes in CMECs treated with exosomes. The miR-29a expression was measured by qRT-PCR, and Western blotting and flow cytometry assays were performed to evaluate the proliferation of CMECs. Results: The results showed that Ang II-induced exosomal miR-29a inhibited the angiogenic ability, migratory function, and proliferation of CMECs. Subsequently, the downstream target gene of miR- 29a, namely, vascular endothelial growth factor (VEGFA), was detected by qRT-PCR and Western blotting, and the results verified that miR-29a targeted the inhibition of the VEGFA expression to subsequently inhibit the angiogenic ability of CMECs. Conclusion: Our results suggest that exosomes derived from Ang II-induced CMs are involved in regulating CMCE proliferation, migration, and angiogenesis by targeting VEGFA through the transfer of miR-29a to CMECs.
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Clinical Observation and Genotype-Phenotype Analysis of ABCA4- Related Hereditary Retinal Degeneration before Gene Therapy
Authors: Xuan Xiao, Lin Ye, Changzheng Chen, Hongmei Zheng and Jiajia YuanBackground: Hereditary retinal degeneration (HRD) is an irreversible eye disease that results in blindness in severe cases. It is most commonly caused by variants in the ABCA4 gene. HRD presents a high degree of clinical and genetic heterogeneity. We determined genotypic and phenotypic correlations, in the natural course of clinical observation, of unrelated progenitors of HRD associated with ABCA4. Objective: To analyze the relationship between the phenotypes and genotypes of ABCA4 variants. Methods: A retrospective clinical study of five cases from the ophthalmology department of the People’s Hospital of Wuhan University from January 2019 to October 2020 was conducted. We tested for ABCA4 variants in the probands. We performed eye tests, including the best-corrected visual acuity, super-wide fundus photography and spontaneous fluorescence photography, optical coherence tomography, and electrophysiological examination. Results: Disease-causing variants were identified in the ABCA4 genes of all patients. Among these, seven ABCA4 variants were novel. All patients were sporadic cases; only one patient had parents who were relatives, and the other four patients were offspring of unrelated parents. Two patients presented with Stargardt disease, mainly with macular lesions, two presented with retinitis pigmentosa (cone-rod type), and one presented with cone dystrophy. The visual acuity and visual field of the five patients showed varying degrees of deterioration and impairment. Conclusion: The same ABCA4 mutation can lead to different clinical phenotypes, and there is variation in the degree of damage to vision, visual field, and electrophysiology among different clinical phenotypes. Clinicians must differentiate between and diagnose pathologies resulting from this mutation.
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AAV9-coGLB1 Improves Lysosomal Storage and Rescues Central Nervous System Inflammation in a Mutant Mouse Model of GM1 Gangliosidosis
Authors: Sichi Liu, Wenhao Ma, Yuyu Feng, Yan Zhang, Xuefang Jia, Chengfang Tang, Fang Tang, Xiaobing Wu and Yonglan HuangBackground: GM1 gangliosidosis (GM1) is an autosomal recessive disorder characterized by the deficiency of beta-galactosidase (β-gal), a ubiquitous lysosomal enzyme that catalyzes the hydrolysis of GM1 ganglioside. Objective: The study aims to explore the application of the AAV9-coGLB1 for effective treatment in a GM1 gangliosidosis mutant mouse model. Methods: We designed a novel adeno-associated virus 9 (AAV9) vector expressing β-gal (AAV9- coGLB1) to treat GM1 gangliosidosis. The vector, injected via the caudal vein at 4 weeks of age, drove the widespread and sustained expression of β-gal for up to 32 weeks in the Glb1G455R/G455R mutant mice (GM1 mice). Results: The increased levels of β-gal reduced the pathological damage occurring in GM1 mice. Histological analyses showed that myelin deficits and neuron-specific pathology were reduced in the cerebral cortex region of AAV9-coGLB1-treated mice. Immunohistochemical staining showed that the accumulation of GM1 ganglioside was also reduced after gene therapy. The reduction of the storage in these regions was accompanied by a decrease in activated microglia. In addition, AAV9 treatment reversed the blockade of autophagic flux in GM1 mice. Conclusion: These results show that AAV9-coGLB1 reduces the pathological signs of GM1 gangliosidosis in a mouse model.
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Volumes & issues
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Volume 25 (2025)
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Volume 24 (2024)
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Volume 23 (2023)
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Volume 22 (2022)
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Volume 21 (2021)
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Volume 20 (2020)
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Volume 19 (2019)
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Volume 18 (2018)
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Volume 17 (2017)
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Volume 16 (2016)
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Volume 15 (2015)
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Volume 14 (2014)
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Volume 13 (2013)
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Volume 12 (2012)
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Volume 11 (2011)
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Volume 10 (2010)
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Volume 9 (2009)
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Volume 8 (2008)
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Volume 7 (2007)
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Volume 6 (2006)
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Volume 5 (2005)
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Volume 4 (2004)
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Volume 3 (2003)
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Volume 2 (2002)
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Volume 1 (2001)
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New Hope for Intervertebral Disc Degeneration: Bone Marrow Mesenchymal Stem Cells and Exosomes Derived from Bone Marrow Mesenchymal Stem Cell Transplantation
Authors: Xiao-bo Zhang, Xiang-yi Chen, Jin Qi, Hai-yu Zhou, Xiao-bing Zhao, Yi-cun Hu, Rui-hao Zhang, De-chen Yu, Xi-dan Gao, Ke-ping Wang and Lin Ma
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