Showing papers by "Jiajia Xue published in 2023"

Bone marrow mesenchymal stem cells loaded into hydrogel/nanofiber composite scaffolds ameliorate ischemic brain injury

Abstract: Central nervous system (CNS) function recovery following stroke remains a major challenge because neural regeneration is difficult to achieve. In this study, rigid-flexible composite scaffolds consisting of nanofibers from electrospun scaffolds and self-adapting and injectable hydrogel were loaded with bone marrow mesenchymal stem cells (BMSCs), and the effects of these loaded BMSCs on ischemic insult were investigated. In vitro analysis of the viability, migration, neurite growth, angiogenic capacity, and paracrine effects of BMSCs indicated that BMSCs loaded in composite scaffolds had a better therapeutic effect than those BMSCs in saline. Furthermore, in vivo, BMSCs loaded in composite scaffolds significantly reduced the extent of brain edema and the infarct volume, alleviated neurological deficits, markedly attenuated microglial and astrocyte overactivation, and increased neuronal proliferation and vascular growth. Bioinformatics analysis revealed that BMSCs loaded in composite scaffolds could decrease the level of exosomal miR-206–3p and consequently increase the activity of the PI3K/AKT signaling pathway. In conclusion, BMSCs loaded in novel composite scaffolds exert obvious neuroprotective effects, attenuating ischemic injury by enhancing angiogenesis and neural regeneration in the brain after ischemic stroke, and these results provide a promising approach for treating CNS diseases in the clinic via cell transplantation.

Endothelial cell-derived exosomes boost and maintain repair-related phenotypes of Schwann cells via miR199-5p to promote nerve regeneration

Abstract: Schwann cells (SCs) respond to nerve injury by transforming into the repair-related cell phenotype, which can provide the essential signals and spatial cues to promote axonal regeneration and induce target reinnervation. Endothelial cells (ECs) contribute to intraneural angiogenesis contributing to creating a permissive microenvironment. The coordination between ECs and SCs within injury sites is crucial in the regeneration process, however, it still unclear. As the intercellular vital information mediators in the nervous system, exosomes have been proposed to take a significant role in regulating regeneration. Thus, the main purpose of this study is to determine the facilitative effect of ECs-derived exosomes on SCs and to seek the underlying mechanism.In the present study, we collected exosomes from media of ECs. We demonstrated that exosomes derived from ECs possessed the favorable neuronal affinity both in vitro and in vivo. Further research indicated that EC-exosomes (EC-EXO) could boost and maintain repair-related phenotypes of SCs, thereby enhancing axonal regeneration, myelination of regenerated axons and neurologically functional recovery of the injured nerve. MiRNA sequencing in EXO-treated SCs and control SCs indicated that EC-EXO significantly up-regulated expression of miR199-5p. Furthermore, this study demonstrated that EC-EXO drove the conversion of SC phenotypes in a PI3K/AKT/PTEN-dependent manner.In conclusion, our research indicates that the internalization of EC-EXO in SCs can promote nerve regeneration by boosting and maintaining the repair-related phenotypes of SCs. And the mechanism may be relevant to the up-regulated expression of miR199-5p and activation of PI3K/AKT/PTEN signaling pathway.

Bioinspired Mild Photothermal Effect-Reinforced Multifunctional Fiber Scaffolds Promote Bone Regeneration.

Abstract: Bone fractures are often companied with poor bone healing and high rates of infection. Early recruitment of mesenchymal stem cells (MSCs) is critical for initiating efficient bone repair, and mild thermal stimulation can accelerate the recovery of chronic diseases. Here, a bioinspired, staged photothermal effect-reinforced multifunctional scaffold was fabricated for bone repair. Uniaxially aligned electrospun polycaprolactone nanofibers were doped with black phosphorus nanosheets (BP NSs) to endow the scaffold with excellent near-infrared (NIR) responsive capability. Apt19S was then decorated on the surface of the scaffold to selectively recruit MSCs toward the injured site. Afterward, microparticles of phase change materials loaded with antibacterial drugs were also deposited on the surface of the scaffold, which could undergo a solid-to-liquid phase transition above 39 °C, triggering the release of payload to eliminate bacteria and prevent infection. Under NIR irradiation, photothermal-mediated up-regulation of heat shock proteins and accelerated biodegradation of BP NSs could promote the osteogenic differentiation of MSCs and biomineralization. Overall, this strategy shows the ability of bacteria elimination, MSCs recruitment, and bone regeneration promotion with the assistance of photothermal effect in vitro and in vivo, which emphasizes the design of a bioinspired scaffold and its potential for a mild photothermal effect in bone tissue engineering.