Thymidylate synthase disruption to limit cell proliferation in cell therapies DOI Creative Commons
Rocío Maldonado, Hossam Montaser, Inkeri Soppa

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: June 26, 2023

Abstract Engineered cells hold great promise for regenerative medicine and gene therapy. However, living cell products entail a fundamental biological risk of unwanted growth. Here, we describe novel metabolic safety system to control proliferation without added genetic elements. We inactivated key enzyme nucleotide metabolism, TYMS , in several lines, thus obtaining that proliferate only when supplemented with exogenous thymidine but fail replicate its absence. Under supplementation, -/- pluripotent stem normally, produce teratomas differentiate into potentially therapeutic types such as pancreatic beta cells. After differentiation, the postmitotic do not require function, seen by prolonged vivo production human insulin implanted mice. Hence, this method allows robust culture manufacture while mitigating uncontrolled growth transplanted One Sentence Summary: Genetic disruption DNA synthesis prevents therapies affecting function.

Language: Английский

Cellular and molecular mechanisms of the blood–brain barrier dysfunction in neurodegenerative diseases DOI Creative Commons

Tongli Chen,

Yan Dai,

Chenghao Hu

et al.

Fluids and Barriers of the CNS, Journal Year: 2024, Volume and Issue: 21(1)

Published: July 19, 2024

Abstract Background Maintaining the structural and functional integrity of blood–brain barrier (BBB) is vital for neuronal equilibrium optimal brain function. Disruptions to BBB performance are implicated in pathology neurodegenerative diseases. Main body Early indicators multiple disorders humans animal models include impaired stability, regional cerebral blood flow shortfalls, vascular inflammation associated with dysfunction. Understanding cellular molecular mechanisms dysfunction crucial elucidating sustenance neural computations under pathological conditions developing treatments these This paper initially explores definition BBB, along signaling pathways regulating flow, inflammation. Subsequently, we review current insights into dynamics Alzheimer’s disease, Parkinson's amyotrophic lateral sclerosis, sclerosis. The concludes by proposing a unified mechanism whereby contributes disorders, highlights potential BBB-focused therapeutic strategies targets, outlines lessons learned future research directions. Conclusions breakdown significantly impacts development progression diseases, unraveling underlying elucidate how sustained devise approaches.

Language: Английский

Citations

28
The role of the blood–brain barrier during neurological disease and infection DOI Creative Commons
Adjanie Patabendige, Damir Janigro

Biochemical Society Transactions, Journal Year: 2023, Volume and Issue: 51(2), P. 613 - 626

Published: March 17, 2023

A healthy brain is protected by the blood–brain barrier (BBB), which formed endothelial cells that line capillaries. The BBB plays an extremely important role in supporting normal neuronal function maintaining homeostasis of microenvironment and restricting pathogen toxin entry to brain. Dysfunction this highly complex regulated structure can be life threatening. dysfunction implicated many neurological diseases such as stroke, Alzheimer's disease, multiple sclerosis, infections. Among other mechanisms, inflammation and/or flow disturbances are major causes infections diseases. In particular, ischaemic both contribute disruption, leading devastating consequences. While a transient or minor disruption could tolerated, chronic total breach result irreversible damage. It worth noting timing extent play process any repair damage treatment strategies. This review evaluates summarises some latest research on during disease infection with focus effects BBB. BBB's crucial protecting also bottleneck central nervous system drug development. Therefore, innovative strategies carry therapeutics across novel models screen drugs, study complex, overlapping mechanisms urgently needed.

Language: Английский

Citations

37
Beneath the radar: immune-evasive cell sources for stroke therapy DOI Creative Commons
Beatriz Achón Buil, Nora H. Rentsch, R. Weber

et al.

Trends in Molecular Medicine, Journal Year: 2024, Volume and Issue: 30(3), P. 223 - 238

Published: Jan. 25, 2024

Stem cell therapy is an emerging treatment paradigm for stroke patients with remaining neurological deficits. While allogeneic transplants overcome the manufacturing constraints of autologous grafts, they can be rejected by recipient's immune system, which identifies foreign cells through human leukocyte antigen (HLA) system. The heterogeneity HLA molecules in population would require a very high number lines, may still inadequate rare genetic HLAs. Here, we outline key progress engineering pluripotent stem and derived to evade host's reducing lines required, examine safety measures explored both preclinical studies upcoming clinical trials.

Language: Английский

Citations

10
Challenges and Material Innovations in Drug Delivery to Central Nervous System Tumors DOI
Zhenyu Gong,

Dairan Zhou,

Dejun Wu

et al.

Biomaterials, Journal Year: 2025, Volume and Issue: 319, P. 123180 - 123180

Published: Feb. 13, 2025

Language: Английский

Citations

1
Revolutionizing Stroke Recovery: Unveiling the Promise of Stem Cell Therapy DOI Creative Commons
Leonidas D Panos, Panagiotis Bargiotas, Marcel Arnold

et al.

Drug Design Development and Therapy, Journal Year: 2024, Volume and Issue: Volume 18, P. 991 - 1006

Published: March 1, 2024

Stem cells, renowned for their unique regenerative capabilities, present significant hope in treating stroke, a major cause of disability globally.This review offers detailed analysis stem cell applications stroke (ischemic and hemorrhagic) recovery.It examines therapies based on autologous (patient-derived), allogeneic (donor-derived), Granulocyte-Colony Stimulating Factor (G-CSF) focusing types such as Mesenchymal Stem/Stromal Cells (MSCs), Bone Marrow Mononuclear (BMMSCs), Neural Stem/Progenitor (NSCs).The paper compiles clinical trial data to evaluate effectiveness safety addresses the ethical concerns these innovative treatments.By explaining mechanisms cell-induced neurological repair, this underscores cells' potential revolutionizing rehabilitation suggests avenues future research.

Language: Английский

Citations

7
Brain repair mechanisms after cell therapy for stroke DOI Creative Commons
Ruslan Rust, Lina R. Nih, Luca Liberale

et al.

Brain, Journal Year: 2024, Volume and Issue: 147(10), P. 3286 - 3305

Published: June 25, 2024

Cell-based therapies hold great promise for brain repair after stroke. While accumulating evidence confirms the preclinical and clinical benefits of cell therapies, underlying mechanisms by which they promote remain unclear. Here, we briefly review endogenous ischaemic stroke then focus on how different stem progenitor sources can repair. Specifically, examine transplanted grafts contribute to improved functional recovery either through direct replacement or stimulating pathways. Additionally, discuss recently implemented refinement methods, such as preconditioning, microcarriers, genetic safety switches universal (immune evasive) transplants, well therapeutic potential these pharmacologic manipulations further enhance efficacy therapies. By gaining a deeper understanding post-ischaemic mechanisms, prospective trials may be refined advance post-stroke therapy clinic.

Language: Английский

Citations

7
The penetration of therapeutics across the blood-brain barrier: Classic case studies and clinical implications DOI Creative Commons
William A. Banks, Elizabeth M. Rhea, May J. Reed

et al.

Cell Reports Medicine, Journal Year: 2024, Volume and Issue: 5(11), P. 101760 - 101760

Published: Oct. 8, 2024

SummaryThe blood-brain barrier (BBB) plays central roles in the maintenance and health of brain. Its mechanisms to safeguard brain against xenobiotics endogenous toxins also make BBB primary obstacle development drugs for nervous system (CNS). Here, we review classic examples intersection clinical medicine, drug delivery, BBB. We highlight role lipid solubility (heroin), saturable brain-to-blood (efflux: opiates) blood-to-brain (influx: nutrients, vitamins, minerals) transport systems, adsorptive transcytosis (viruses incretin receptor agonists). examine how disruption that occurs certain diseases (tumors) can be modulated (osmotic agents microbubbles) used deliver treatments, extracellular pathways gaining access CNS (albumin antibodies). In summary, this provides a historical perspective key delivery disease.Graphical abstract

Language: Английский

Citations

6
Emerging strategies for nerve repair and regeneration in ischemic stroke: neural stem cell therapy DOI Creative Commons
Siji Wang,

Qianyan He,

Yang Qu

et al.

Neural Regeneration Research, Journal Year: 2023, Volume and Issue: 19(11), P. 2430 - 2443

Published: Dec. 21, 2023

Ischemic stroke is a major cause of mortality and disability worldwide, with limited treatment options available in clinical practice. The emergence stem cell therapy has provided new hope to the field via restoration brain neuron function. Exogenous neural cells are beneficial not only replacement but also through bystander effect. Neural regulate multiple physiological responses, including nerve repair, endogenous regeneration, immune function, blood-brain barrier permeability, secretion bioactive substances, extracellular vesicles/exosomes. However, due complex microenvironment ischemic cerebrovascular events low survival rate following transplantation, limitations effect remain unresolved. In this paper, we provide detailed summary potential mechanisms for stroke, review current therapeutic strategies trial results, summarize latest advancements engineering improve cells. We that could help insight into guide future scientific endeavors on

Language: Английский

Citations

11
Circulatory factors in stroke protection and recovery DOI

Jiachen He,

Qi Liu,

Jiaqi Guo

et al.

Brain Research, Journal Year: 2025, Volume and Issue: unknown, P. 149594 - 149594

Published: March 1, 2025

Language: Английский

Citations

0
Ischemic stroke-related gene expression profiles across species: a meta-analysis DOI Creative Commons
Ruslan Rust

Journal of Inflammation, Journal Year: 2023, Volume and Issue: 20(1)

Published: June 19, 2023

Stroke patients are often left with permanent disabilities no regenerative treatment options. Unbiased RNA sequencing studies decoding the transcriptional signature of stroked tissue hold promise to identify new potential targets and pathways directed improve for stroke patients. Here, gene expression profiles across different time points, species, models were compared using NCBI GEO database. In total, 34 datasets from mice, rats, humans, primates included, exploring differences in healthy brain tissue. Distinct changes pathway enrichment revealed heterogenicity pathology stroke-related e.g., inflammatory responses, vascular repair, remodelling cell proliferation adhesion but also diverse general, stroke-unrelated that have be carefully considered when evaluating promising therapeutic targets.

Language: Английский

Citations

10