A redox-reactive delivery system via neural stem cell nanoencapsulation enhances white matter regeneration in intracerebral hemorrhage mice.
Xuejiao LeiQuan HuHongfei GeXuyang ZhangXufang RuYujie ChenRong HuHua FengJun DengYan HuangWenyan LiPublished in: Bioengineering & translational medicine (2022)
Intracerebral hemorrhage (ICH) poses a great threat to human health because of its high mortality and morbidity. Neural stem cell (NSC) transplantation is promising for treating white matter injury following ICH to promote functional recovery. However, reactive oxygen species (ROS)-induced NSC apoptosis and uncontrolled differentiation hindered the effectiveness of the therapy. Herein, we developed a single-cell nanogel system by layer-by-layer (LbL) hydrogen bonding of gelatin and tannic acid (TA), which was modified with a boronic ester-based compound linking triiodothyronine (T3). In vitro, NSCs in nanogel were protected from ROS-induced apoptosis, with apoptotic signaling pathways downregulated. This process of ROS elimination by material shell synergistically triggered T3 release to induce NSC differentiation into oligodendrocytes. Furthermore, in animal studies, ICH mice receiving nanogels performed better in behavioral evaluation, neurological scaling, and open field tests. These animals exhibited enhanced differentiation of NSCs into oligodendrocytes and promoted white matter tract regeneration on Day 21 through activation of the αvβ3/PI3K/THRA pathway. Consequently, transplantation of LbL(T3) nanogels largely resolved two obstacles in NSC therapy synergistically: low survival and uncontrolled differentiation, enhancing white matter regeneration and behavioral performance of ICH mice. As expected, nanoencapsulation with synergistic effects would efficiently provide hosts with various biological benefits and minimize the difficulty in material fabrication, inspiring next-generation material design for tackling complicated pathological conditions.
Keyphrases
- white matter
- stem cells
- reactive oxygen species
- cell death
- induced apoptosis
- multiple sclerosis
- endoplasmic reticulum stress
- human health
- cell therapy
- signaling pathway
- oxidative stress
- dna damage
- high fat diet induced
- risk assessment
- single cell
- brain injury
- randomized controlled trial
- climate change
- cell cycle arrest
- minimally invasive
- cardiovascular events
- rna seq
- coronary artery disease
- epithelial mesenchymal transition
- diabetic rats
- wild type
- endothelial cells
- adipose tissue
- cardiovascular disease
- pi k akt
- case control
- replacement therapy