Engineered Mesenchymal Stem Cells Over-Expressing BDNF Protect the Brain from Traumatic Brain Injury-Induced Neuronal Death, Neurological Deficits, and Cognitive Impairments

Choi, Bo Young; Hong, Dae Ki; Kang, Beom Seok; Lee, Si Hyun; Choi, Seung–Hyuk; Kim, Hyojin; Lee, Soon Min; Suh, Sang Won

doi:10.3390/ph16030436

Cited by 8 publications

(3 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Engineered MSCs overexpressing BDNF were intracerebroventricularly administered directly into the left lateral ventricle of the brain, ultimately improving the neurological and cognitive functions of traumatic brain injury rats in the Morris water maze test compared to a negative control. Thus, it was suggested that engineered MSCs secreted significantly more BDNF than naïve MSCs [ 78 ]. (iii) Fibroblast growth factor 21 (FGF21) is a type of secreted growth factor that acts as a metabolic regulator by binding to fibroblast growth factor receptors.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal Stem Cell (MSC)-Based Drug Delivery into the Brain across the Blood–Brain Barrier

Tashima

2024

Pharmaceutics

View full text Add to dashboard Cite

At present, stem cell-based therapies using induced pluripotent stem cells (iPSCs) or mesenchymal stem cells (MSCs) are being used to explore the potential for regenerative medicine in the treatment of various diseases, owing to their ability for multilineage differentiation. Interestingly, MSCs are employed not only in regenerative medicine, but also as carriers for drug delivery, homing to target sites in injured or damaged tissues including the brain by crossing the blood–brain barrier (BBB). In drug research and development, membrane impermeability is a serious problem. The development of central nervous system drugs for the treatment of neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease, remains difficult due to impermeability in capillary endothelial cells at the BBB, in addition to their complicated pathogenesis and pathology. Thus, intravenously or intraarterially administered MSC-mediated drug delivery in a non-invasive way is a solution to this transendothelial problem at the BBB. Substances delivered by MSCs are divided into artificially included materials in advance, such as low molecular weight compounds including doxorubicin, and expected protein expression products of genetic modification, such as interleukins. After internalizing into the brain through the fenestration between the capillary endothelial cells, MSCs release their cargos to the injured brain cells. In this review, I introduce the potential and advantages of drug delivery into the brain across the BBB using MSCs as a carrier that moves into the brain as if they acted of their own will.

show abstract

Section: Discussionmentioning

confidence: 99%

Mesenchymal Stem Cell (MSC)-Based Drug Delivery into the Brain across the Blood–Brain Barrier

Tashima

2024

Pharmaceutics

View full text Add to dashboard Cite

show abstract

“…TBI is a leading cause of death and disability in patients of all ages [36][37][38][39]. Nowadays, prevention of secondary injury has become an important step in the treatment of TBI [40,41]. It has been shown that iron overload is highly involved in the pathophysiological process of secondary brain injury [42] and that increased iron accumulation in the brain leads to lipid peroxidation, ROS production, resulting in cellular and neuronal damage [2].…”

Section: Discussionmentioning

confidence: 99%

A ROS-responsive loaded desferoxamine (DFO) hydrogel system for traumatic brain injury therapy

Qiu,

Zeng,

Zhang

et al. 2024

Biomed. Mater.

View full text Add to dashboard Cite

Traumatic brain injury (TBI) produces excess iron, and increased iron accumulation in the brain leads to lipid peroxidation and reactive oxygen species (ROS), which can exacerbate secondary damage and lead to disability and death. Therefore, inhibition of iron overload and oxidative stress has a significant role in the treatment of TBI. Functionalized hydrogels with iron overload inhibiting ability and of oxidative stress inhibiting ability will greatly contribute to the repair of TBI. Herein, an injectable, post-traumatic microenvironment-responsive, ROS-responsive hydrogel encapsulated with deferrioxamine mesylate (DFO) was developed. The hydrogel is rapidly formed via dynamic covalent bonding between phenylboronic acid grafted hyaluronic acid (HA-PBA) and polyvinyl alcohol (PVA), and phenylboronate bonds are used to respond to and reduce ROS levels in damaged brain tissue to promote neuronal regeneration and recovery. The release of DFO from HA-PBA/PVA hydrogels in response to ROS further promotes neuronal regeneration and recovery by relieving iron overload and thus eradicating ROS. In the Feeney model of Sprague Dawley (SD) rats, HA-PBA/PVA/DFO hydrogel treatment significantly improved the behavior of TBI rats and reduced the area of brain contusion in rats. In addition, HA-PBA/PVA/DFO hydrogel significantly reduced iron overload to reduce ROS and could effectively promote post-traumatic neuronal recovery. Its effects were also explored, and notably, HA-PBA/PVA/DFO hydrogel can reduce iron overload as well as ROS, thus protecting neurons from death. Thus, this injectable, biocompatible and ROS-responsive drug-loaded hydrogel has great potential for the treatment of TBI. This work suggests a novel method for the treatment of secondary brain injury by inhibiting iron overload and the oxidative stress response after TBI.

show abstract

“…Nerve cell death stands as a significant contributor to neurological disorders, diseases, and injuries. The unexpected or programmed demise of neurons and glial cells across various regions of the nervous system disrupts sensory, motor, cognitive, learning, and memory functions [1][2][3]. Ferroptosis, a form of regulated cell death triggered by iron overload, involves distinct inducible factors and metabolites [4].…”

Section: Introductionmentioning

confidence: 99%

The Interplay between Ferroptosis and Neuroinflammation in Central Neurological Disorders

Xu,

Jia,

et al. 2024

Antioxidants

View full text Add to dashboard Cite

Central neurological disorders are significant contributors to morbidity, mortality, and long-term disability globally in modern society. These encompass neurodegenerative diseases, ischemic brain diseases, traumatic brain injury, epilepsy, depression, and more. The involved pathogenesis is notably intricate and diverse. Ferroptosis and neuroinflammation play pivotal roles in elucidating the causes of cognitive impairment stemming from these diseases. Given the concurrent occurrence of ferroptosis and neuroinflammation due to metabolic shifts such as iron and ROS, as well as their critical roles in central nervous disorders, the investigation into the co-regulatory mechanism of ferroptosis and neuroinflammation has emerged as a prominent area of research. This paper delves into the mechanisms of ferroptosis and neuroinflammation in central nervous disorders, along with their interrelationship. It specifically emphasizes the core molecules within the shared pathways governing ferroptosis and neuroinflammation, including SIRT1, Nrf2, NF-κB, Cox-2, iNOS/NO·, and how different immune cells and structures contribute to cognitive dysfunction through these mechanisms. Researchers’ findings suggest that ferroptosis and neuroinflammation mutually promote each other and may represent key factors in the progression of central neurological disorders. A deeper comprehension of the common pathway between cellular ferroptosis and neuroinflammation holds promise for improving symptoms and prognosis related to central neurological disorders.

show abstract

Engineered Mesenchymal Stem Cells Over-Expressing BDNF Protect the Brain from Traumatic Brain Injury-Induced Neuronal Death, Neurological Deficits, and Cognitive Impairments

Cited by 8 publications

References 67 publications

Mesenchymal Stem Cell (MSC)-Based Drug Delivery into the Brain across the Blood–Brain Barrier

Mesenchymal Stem Cell (MSC)-Based Drug Delivery into the Brain across the Blood–Brain Barrier

A ROS-responsive loaded desferoxamine (DFO) hydrogel system for traumatic brain injury therapy

The Interplay between Ferroptosis and Neuroinflammation in Central Neurological Disorders

Contact Info

Product

Resources

About