Upregulating HIF‐1α to Boost the Survival of Neural Stem Cells via Functional Peptides‐Complexed MRI‐Visible Nanomedicine for Stroke Therapy

Abstract

Neural stem cells (NSCs) transplantation has been considered as a promising strategy for the treatment of ischemic stroke. However, the therapeutic prospect is limited by the poor control over the survival, migration, and maturation of transplanted NSCs. Upregulating hypoxia inducible factor (HIF)-1𝜶 expression in stem cells can improve the survival and migration of NSCs grafted for stroke therapy. Functional peptide drugs, which could inhibit endogenous HIF-1𝜶 ubiquitination, might be used to effectively upregulate the HIF-1𝜶 expression in NSCs, thereby to improve the therapeutic effect in ischemia stroke. Herein, a magnetic resonance imaging (MRI)-visible nanomedicine is developed to codeliver functional peptides and superparamagnetic iron oxide (SPIO) nanoparticles into NSCs. This nanomedicine not only promotes the survival and migration ability of NSCs but also allows an in vivo tracking of transplanted NSCs with MRI. The results demonstrate the great potential of the functional peptides-complexed multifunctional nanomedicine in boosting the therapeutic effect of stem cell-based therapy in stroke.

State of the Art and Future of Stem Cell Therapy in Ischemic Stroke: Why Don’t We Focus on Their Administration?

“…Transplanted mice revealed less volume of infarction one week post-surgery, while two weeks later, the ratio of apoptotic cells was inferior in NSCs treated with the functional peptide. Indeed, more NSCs positive for nestin and CXCR4 were found around the transplanted area, and they seemed to migrate efficiently to the cortex [46].…”

Stem cell-based ischemic stroke therapy: Novel modifications and clinical challenges

“…Interestingly, studies have found that the hypoxia-inducible factor-1 (HIF-1) can regulate SDF-1 gene expression [94] . Augmenting HIF-1α expression can improve survival rates of SC in ischemic regions [95] , which partly explains why certain hypoxic preconditioning can enhance SC homing.…”

“…For instance, Tang et al developed a melanin nanoparticle that enhances MSCs’ therapeutic ability against hypoxic-ischemic injury by up-regulating antioxidant defense and inhibiting apoptosis [137] . Interestingly, nanoparticle-modified SCs can enhance survival [95 , 138] and neural differentiation abilities [139] during IS therapy. Among them, nanoparticles formed through functional peptide and SPION self-assembly were delivered into cells, and functional peptides up-regulated HIF-1α and induced a higher NSC survival rate.…”

Advanced Nano-Drug Delivery Systems in the Treatment of Ischemic Stroke

“…In vitro cellular experiments demonstrated that Fe 3 O 4 nanoenzymes were effective in ameliorating neuroinflammation caused by ISs, as well as significantly reducing the infarct volume in both transient and permanent stroke models. Wang et al developed an MRI visualization technique to track and visualize transplanted stem cells, offering valuable insights to enhance the effectiveness of IS treatment [148]. Similarly, some studies used superparamagnetic iron oxide nanoparticles (SPIO) to label stem cells for imaging tracking in IS therapy [107,149,150].…”