Human Bone Marrow-Derived Mesenchymal Stem Cell Applications in Neurodegenerative Disease Treatment and Integrated Omics Analysis for Successful Stem Cell Therapy

Kim, Seok Gi; George, Nimisha Pradeep; Hwang, Ji Su; Park, Seok-Ho; Kim, Myeong Ok; Lee, Soo Hwan; Lee, Gwang

doi:10.3390/bioengineering10050621

Cited by 6 publications

(6 citation statements)

References 134 publications

(175 reference statements)

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“…Stem cell transplantation is emerging as a promising treatment for ischemic diseases, as research has confirmed the beneficial therapeutic effects of stem cells in both clinical and experimental models [ 34 ]. Among various stem cells, adult mesenchymal stem cells (MSCs), particularly bone marrow-derived stem cells (BMSCs), show potential due to their high self-renewal, differentiation capacity, and low immunogenicity for the treatment of ischemic diseases [ 35 , 36 ]. Limitations include restricted available BMSCs from patients and an age-related decline in their proliferation and differentiation potential.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective Effects of Human-Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cell Extracellular Vesicles in Ischemic Stroke Models

Lu,

Su,

Wang

et al. 2023

Biomedicines

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Background: Stroke represents the second leading cause of death and the primary cause of long-term disability in humans. The transplantation of mesenchymal stem cells (MSC) reportedly improves functional outcomes in animal models of cerebral ischemia. Here, we evaluate the neuroprotective potential of extracellular vesicles secreted from human-induced pluripotent stem cell-derived mesenchymal stem cells (hiPS-MSC-EV) using preclinical cell-based and animal-based models of ischemic strokes. Methods: hiPS-MSC-EV were isolated using an ultrafiltration method. HT22 cells were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) injury for 2 h, followed by treatment with hiPS-MSC-EV (100 μg/mL). Male C57BL/6 mice were subjected to middle cerebral artery occlusion (MCAO) followed by an intravenous injection of hiPS-MSC-EV (100 μg) at three distinct time points. Results: Our experimental approach revealed hiPS-MSC-EV promoted HT22 cell proliferation, reduced apoptosis, and altered cellular morphology following OGD/R. In addition, hiPS-MSC-EV reduced the volume of infarcts, improved spontaneous movement abilities, and enhanced angiogenesis by expressing the VEGF and CXCR4 proteins in the infarcted hemisphere of the MCAO-treated mouse model. Conclusion: Our findings provide evidence of the potential neuroprotective effects of hiPS-MSC-derived extracellular vesicles (hiPS-MSC-EVs) in both in vitro and in vivo mouse models of ischemic stroke. These results suggest that hiPS-MSC-EVs may play a role in neurorestoration and offer insights into potential cell-free strategies for addressing cerebral ischemia.

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Section: Discussionmentioning

confidence: 99%

Neuroprotective Effects of Human-Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cell Extracellular Vesicles in Ischemic Stroke Models

Lu,

Su,

Wang

et al. 2023

Biomedicines

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“…Primary approaches under exploration for utilizing these vesicles in treatments encompass strategies like using vesicle-releasing cells on-site, injecting purified or modified vesicles, and implanting modified cells that produce tailored vesicles within the body [102][103][104]. Examples include investigating mesenchymal stem cell-derived vesicles for treating conditions like cerebellar ataxia, bone repair, and eye issues [105,106]. Additionally, there has been extensive research into loading isolated vesicles with specific substances or modifying their surfaces for enhanced delivery, targeting ailments such as stroke and pancreatic cancer [99,100,107].…”

Section: Applications Of Extracellular Vesiclesmentioning

confidence: 99%

Extracellular Vesicles: Tiny Messengers for Mighty RNA Delivery

Das

2024

Biologics

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Extracellular vesicles (EVs) encompass a diverse array of cell-derived vesicles, originating either from the endosomal compartment (exosomes) or generated through shedding from the cell membrane. These lipid bilayer nanovesicles carry a diverse cargo consisting of nucleic acids, various macromolecules, and growth factors, capable of being assimilated by nearby or distant cells through biofluids, thereby triggering a wide range of cellular responses. Given their distinctive biological characteristics and crucial roles in intercellular communication, EVs have garnered significant attention, especially concerning potential clinical applications. Inheriting cargo from their parent cells, EVs present promising resources for diverse disease biomarkers. Research elucidating the specific impacts of cargo on target cells has sparked enthusiasm for their therapeutic potential. Compelling evidence indicates that RNA cargo housed within EVs can modulate gene expression and influence cellular functions in recipient cells. However, despite significant progress, numerous aspects of EV biology remain obscure, encompassing selective cargo-loading mechanisms that yield distinct compositions from source cells, variability in size and content, and undisclosed pathways governing uptake and cargo fate in recipient cells. A thorough understanding of core EV mechanisms—such as generation, trafficking, and payload delivery—is essential for their effective clinical utilization. This review explores the current understanding of RNA loading and transportation within EVs, shedding light on the advancements made toward clinical applications.

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“…Parkinson's disease (PD) and multiple sclerosis are chronic, progressive neurodegenerative pathologies that are quite common in Ukraine and tend to increase [1,2]. Today, the transplantation of multipotent mesenchymal stromal cells (MMSCs) from various sources, in particular bone marrow, is an important direction of cell therapy for the above-mentioned pathologies [3][4][5]. This is related to the biological properties of MMSCs, namely the ability to multilineage differentiation, the synthesis of neurotrophic factors, anti-inflammatory, antioxidant and immunomodulatory effects.…”

Section: Abstract: Parkinson's Disease/parkinsonism; Multiple Scleros...mentioning

confidence: 99%

“…Bone marrow cells were obtained from mice of each group on the 18 th day of the experiment and incubated for 12 days to further evaluate the colony-forming ability of stromal progenitor cells [21]. It is MMSCs that are successfully used in cell therapy of neurodegenerative pathology [3]. Bone marrow cells (1×10 6 ) of FVB/N and 129/Sv mice, which were injected with MPTP, were incubated with melatonin (Sigma, USA) at a dose of 0.1 μg/0.1 mL or without it.…”

Section: Animalsmentioning

confidence: 99%

Colony-forming potential of murine bone marrow-derived progenitor cells in experimental neurodegenerative pathology and under the impact of melatonin in vivo or in vitro

Labunets,

Ustymenko,

Panteleymonova

et al. 2024

COT

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Cell therapy is a promising direction in the treatment of Parkinson’s disease/parkinsonism and multiple sclerosis, the effectiveness of which can be increased with the help of biologically active factors, in particular melatonin. The purpose of the study: to investigate the colony-forming ability of stromal and hematopoietic cells-progenitors of the bone marrow of mice with experimentally induced neurodegenerative pathology and reveal the possibility to change it under the influence of melatonin in vivo or in vitro. Materials and methods: In adult (6-7 months) male FVB/N (haplotype H-2q) and 129/Sv (haplotype H-2b) mice, the parkinsonism model was reproduced by a single subcutaneous injection of the neurotoxin 1-methyl-4-phenyl -1,2,3,6-tetrahydropyridine (MPTP) at a dose of 30 mg/kg 129/Sv mice also received the neurotoxin cuprizone daily with food (at the rate of 0.2 % of the mass of the pure substance from the daily feed) for three weeks (multiple sclerosis model). Melatonin was administered to the 129/Sv mice intraperitoneally at a dose of 1 mg/kg, daily, at 17.00, from the 8th day of receiving cuprizone, or was added in vitro to the culture of bone marrow cells of mice of both strains with parkinsonism at a dose of 0.1 μg/0.1 mL. In the bone marrow, the absolute number of nucleated cells was counted, the relative content of CD4+ lymphocytes was determined by flow cytometry, and the number of colony-forming precursor cells for fibroblasts (CFU-F) and for granulocyte-macrophages (CFU-GM) in culture in vitro was estimated. Results. In the bone marrow of 129/Sv mice with a model of multiple sclerosis, the number of nucleated cells, CFU-GM and CD4+ cells decrease, while under the influence of exogenous melatonin applied in vivo, the values of these indicators increase to the level of intact animals. After the administration of MPTP in the bone marrow of FVB/N mice, in contrast to 129/Sv mice, the number of nucleated cells and CFU-F decreases. After the incubation with melatonin of bone marrow cells of 129/Sv mice with a model of parkinsonism, an increase in the amount of CFU-F was observed compared to control values, and there were no changes in the indicator values in FVB/N mice. Conclusions. In the bone marrow of mice with the MPTP-model of parkinsonism, a decrease in the absolute amount of CFU-F was found, and in mice with the cuprizone model of multiple sclerosis – CFU-GM. The application of melatonin in vitro increases the colony-forming potential of progenitor cells for fibroblasts in the bone marrow of mice with the MPTP model of parkinsonism. The use of melatonin in vivo increases the colony-forming ability of progenitor cells for granulocyte-macrophages and the relative content of CD4+ cells in the bone marrow of mice with the cuprizone model of multiple sclerosis. Changes in the amount of CFU-F in the bone marrow in parkinsonism and under the influence of melatonin in vitro depend on the H-2 haplotype mice, which can be the basis for the development of personalized cell therapy for this pathology.

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Human Bone Marrow-Derived Mesenchymal Stem Cell Applications in Neurodegenerative Disease Treatment and Integrated Omics Analysis for Successful Stem Cell Therapy

Cited by 6 publications

References 134 publications

Neuroprotective Effects of Human-Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cell Extracellular Vesicles in Ischemic Stroke Models

Neuroprotective Effects of Human-Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cell Extracellular Vesicles in Ischemic Stroke Models

Extracellular Vesicles: Tiny Messengers for Mighty RNA Delivery

Colony-forming potential of murine bone marrow-derived progenitor cells in experimental neurodegenerative pathology and under the impact of melatonin in vivo or in vitro

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