Human stem cell transplantation models of Alzheimer’s disease

Frontiers in Aging Neuroscience, Год журнала: 2024, Номер 16

Опубликована: Фев. 21, 2024

Alzheimer’s disease (AD) is the most frequent form of dementia. It characterized by pronounced neuronal degeneration with formation neurofibrillary tangles and deposition amyloid β throughout central nervous system. Animal models have provided important insights into pathogenesis AD they shown that different brain cell types including neurons, astrocytes microglia functions in AD. However, there are difficulties translating promising therapeutic observations mice clinical application patients. Alternative using human cells such as induced pluripotent stem (iPSCs) may provide significant advantages, since successfully been used to model mechanisms neurons glial neurodegenerative diseases vitro vivo . In this review, we summarize recent studies describe transplantation iPSC-derived microglial forebrain generate chimeric We also discuss opportunities, challenges limitations differentiated iPSCs for modeling their biomedical research.

Язык: Английский

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Replicative Senescence in Mesenchymal Stem Cells: An In Vitro Study on Mitochondrial Dynamics and Metabolic Alterations

Antioxidants, Год журнала: 2025, Номер 14(4), С. 446 - 446

Опубликована: Апрель 8, 2025

Mesenchymal stem cells (MSCs) are multipotent progenitors capable of self-renewal and differentiation into various cell lineages, making them essential for tissue repair regenerative medicine. However, their potential is constrained by replicative senescence, an irreversible growth arrest that occurs after a finite number divisions. In this study, we serially passaged human bone marrow-derived MSCs (bMSCs) compared young, pre-senescent, senescent cells. The onset senescence was accompanied progressive alterations in mitochondrial dynamics, leading to decline membrane potential, increased reactive oxygen species (ROS) production, alongside diminished cellular antioxidant capacity. These defects play role metabolic reprogramming bMSCs. Our findings underscore the intricate interplay between ROS, dysfunction, offering valuable insights guide development therapeutic strategies preserving MSC functionality aging MSC-based therapies.

Язык: Английский

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Reprogramming iPSCs to study age-related diseases: Models, therapeutics, and clinical trials

Mechanisms of Ageing and Development, Год журнала: 2023, Номер 214, С. 111854 - 111854

Опубликована: Авг. 12, 2023

Язык: Английский

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Model Systems to Study the Mechanism of Vascular Aging

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(20), С. 15379 - 15379

Опубликована: Окт. 19, 2023

Cardiovascular diseases are the leading cause of death globally. Within cardiovascular aging, arterial aging holds significant importance, as it involves structural and functional alterations in arteries that contribute substantially to overall decline health during process. As age, their ability respond stress injury diminishes, while luminal diameter increases. Moreover, they experience intimal medial thickening, endothelial dysfunction, loss vascular smooth muscle cells, cellular senescence, extracellular matrix remodeling, deposition collagen calcium. This process also leads stiffening remodeling. The genomic instability plays a vital role accelerating aging. Progeria syndromes, rare genetic disorders causing premature exemplify impact instability. Throughout life, our DNA faces constant challenges from environmental radiation, chemicals, endogenous metabolic products, damage genome we age. accumulation unrepaired damages over time manifests an phenotype. To study various models available, ranging vivo mouse studies cell culture options, there microfluidic vitro model systems known vessels-on-a-chip. Together, these offer valuable insights into blood vessels.

Язык: Английский

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Long-term passage impacts human dental pulp stem cell activities and cell response to drug addition in vitro

PeerJ, Год журнала: 2024, Номер 12, С. e17913 - e17913

Опубликована: Авг. 23, 2024

Background Dental pulp stem cells (DPSCs) possess mesenchymal cell characteristics and have potential for cell-based therapy. Cell expansion is essential to achieve sufficient numbers. However, continuous replication causes aging in vitro , which usually accompanies potentially affect DPSC activities. Continuous passaging could alter susceptibility external factors such as drug treatment. Therefore, this study sought investigate outcome of on morphology activities the absence or presence factor. Methods Human DPSCs were subcultured until reaching early passages (P5), extended (P10), late (P15). Cells evaluated compared nuclear morphologies, adhesion, proliferative capacity, alkaline phosphatase (ALP) activity, gene expressions Alendronate (ALN) treatment was used an Results gradually lost their normal spindle shape increased sizes. vulnerable ALN. The size altered, leading morphological abnormality inhomogeneity. Long-term culture ALN interfered with adhesion. able proliferate irrespective but rate proliferation slower. at moderate dose inhibited growth. caused reduction ALP activity passage. In contrast, passage responded differently by increasing activity. Late showed higher collagen lower osteocalcin Conclusion An increase number played critical role well responses addition effects should be considered when basic science research clinical applications.

Язык: Английский

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Senescence Model Theories from In Vitro through In Vivo

Düzce Tıp Fakültesi Dergisi, Год журнала: 2024, Номер 26(S1), С. 95 - 99

Опубликована: Июнь 13, 2024

The theoretical equivalence of expressing that a cell is aging to its inability perform the assumed function not exactly accurate, it involves gradual decrease in mechanisms. Factors such as genetics, lifestyle, and environmental effects maintain biological change cell. concept cellular senescence was initially introduced by Hayflick his collaborators 1961 when they noticed human diploid fibroblasts cultured vitro could undergo only limited number divisions before their ability proliferate permanently halted. This phenomenon, known 'Hayflick limit', subsequently linked shortening telomeres with each successive round division. Throughout process, senescent cells collect different tissues. Their involvement age-related health issues neurodegenerative disorders, heart problems, cancer, kidney-related changes, chronic lung diseases, osteoarthritis suggests targeting therapeutically be promising across various conditions. review will discuss available data on which types may based how these processes impact age-associated tissue-specific pathologies. Additionally, markers used characterize physiological transition from vivo settings evaluated. discussed serve significant starting point for an expanded definition molecular functional characteristics organs, thus supporting development enhancement strategies vivo.

Язык: Английский

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Widespread naturally variable human exons aid genetic interpretation

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Сен. 11, 2024

Abstract Most mammalian genes undergo alternative splicing. The splicing of some exons has been acquired or lost in specific lineages, but differences within the human population are poorly characterized. Using GTEx tissue transcriptomes from 838 individuals, we identified 56,415 which included mRNAs individuals entirely excluded others, term “naturally variable exons” (NVEs). NVEs impact three quarters protein-coding genes, occur at all frequencies, and often absent reference annotations. more abundant depleted genetic loss-of-function mutations aid interpretation causal variants. Genetic variants modulate many NVEs, 5’UTR coding-region associated with increased decreased gene expression, respectively. Together, our findings characterize variation population, implications for a range analyses.

Язык: Английский

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Establishing immortalized brown and white preadipocyte cell lines from young and aged mice

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Окт. 11, 2024

Abstract Studying adipogenesis and adipocyte biology requires the isolation of primary preadipocytes from adipose tissues. However, have a limited lifespan, can only undergo finite number divisions, often lose their original biological characteristics before becoming senescent. The repeated fresh preadipocytes, particularly young pups or aged animals, is costly time-consuming. Immortalization these cells offers solution by overcoming cellular senescence maintaining proliferative capacity, allowing for long-term studies without continuous need to isolate new animals. Immortalized cell lines thus provide consistent reproducible experimental model, significantly reducing variability across different successfully establishing immortalized preadipocyte presents challenges, including selecting appropriate tissue depots, isolating choosing an effective immortalization strategy. In this study, we present optimized protocols share first-hand experiences brown white aging mice. These offer valuable resource researchers studying adipogenesis, metabolism, biology. Support Protocol 1 : Retrovirus production Basic Isolation culture mouse interscapular (iBAT) subcutaneous (sWAT) in same region 2 3 Selection 4 single-cell clones Cryopreservation Wake up Subculture expansion 5 Differentiation Lipid droplet staining nucleus counterstaining 6 Mitochondria

Язык: Английский

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Establishing Immortalized Brown and White Preadipocyte Cell Lines from Young and Aged Mice

Current Protocols, Год журнала: 2024, Номер 4(12)

Опубликована: Дек. 1, 2024

Abstract Studying adipogenesis and adipocyte biology requires the isolation of primary preadipocytes from adipose tissues. However, have a limited lifespan, can only undergo finite number divisions, often lose their original biological characteristics before becoming senescent. The repeated fresh preadipocytes, particularly young pups or aged animals, is costly time consuming. Immortalization these cells offers solution by overcoming cellular senescence maintaining proliferative capacity, allowing for long‐term studies without continuous need to isolate new animals. Immortalized cell lines thus provide consistent reproducible experimental model, significantly reducing variability across different successfully establishing immortalized preadipocyte presents challenges, including selecting appropriate tissue depots, isolating choosing an effective immortalization strategy. In this article, we present optimized protocols share first‐hand experiences brown white aging mice. These offer valuable resource researchers studying metabolism. © 2024 Wiley Periodicals LLC. Support Protocol 1 : Retrovirus production Basic Isolation culture mouse interscapular (iBAT) subcutaneous (sWAT) in same region 2 3 Selection 4 single‐cell clones 5 Single‐cell sorting 96‐well plate using flow cytometer selection Cryopreservation Thawing cryopreserved Subculture expansion 6 Differentiation Identification differentiated adipocytes

Язык: Английский

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Human Liver MSCs Retain Their Basic Cellular Properties in Chronically Inflamed Liver Tissue

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(24), С. 13374 - 13374

Опубликована: Дек. 13, 2024

Every 25th death worldwide is associated with liver pathology. The development of novel approaches to diseases therapy and protocols for maintaining the vital functions patients on transplant waiting list are urgently needed. Resident mesenchymal stem cells (MSCs) play a significant role in supporting tissue integrity improve condition after infusion. However, it remains unclear whether MSCs isolated from chronically inflamed livers similar their basic cellular properties obtained healthy livers. We applied large array tests compare resident apparently normal fibrosis, cirrhosis, viral hepatitis. Chronic inflammatory environment did not alter major characteristics MSCs, including expression MSC markers, cell adhesion molecules, hallmarks senescence, as well proliferation, migration, secretome. Only some immune checkpoints toll-like receptors was different. Evidently, unchanged present human even at late stages diseases. These can be used starting material therapies

Язык: Английский

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