Plant Exosomes As Novel Nanoplatforms for MicroRNA Transfer Stimulate Neural Differentiation of Stem Cells In Vitro and In Vivo

Abstract

Differentiation of bone marrow derived mesenchymal stem cells (BMSCs) into functional neural cells has been widely investigated for treating neural diseases. However, the limited neural differentiation of BMSCs remains a big challenge to overcome. Herein, for the first time, ginseng-derived exosomes (G-Exos) were demonstrated to have excellent efficiency in stimulating the neural differentiation of BMSCs by transferring the incorporated miRNAs to BMSCs efficiently. In vivo, a photocross-linkable hydrogel with chemokine and G-Exos loaded shows strong efficacy in recruiting and directing the neural differentiation of BMSCs in the program. G-Exos were demonstrated to be promising nanoplatforms in transferring plant-derived miRNAs to mammalian stem cells for neural differentiation both in vitro and in vivo, possessing great potential in neural regenerative medicine.

Hydrogels for Exosome Delivery in Biomedical Applications

“…Li et al improved the affinity of HA hydrogels and MSC-derived exosomes by a laminin modification, and successfully promoted spinal cord regeneration and the recovery of hindlimb motor function in vivo [ 119 ]. Surprisingly, plant (e.g., ginseng)-derived exosomes that can stimulate the neural differentiation of BMSCs have been demonstrated, and can be loaded in GelMA to fit the irregular shapes of injury defects [ 138 ]. The promotion of angiogenesis is beneficial for the regeneration of neuronal networks after SCI.…”

Extracellular Vesicles: Emerging Roles in Developing Therapeutic Approach and Delivery Tool of Chinese Herbal Medicine for the Treatment of Depressive Disorder

“…For example, EVs-liked ginseng-derived nanoparticles (GDNPs) can be recognized and internalized with macrophages and induce M1-type polarization of macrophages to inhibit melanoma growth in mice ( Cao et al, 2019c ). Exosomes derived from ginseng can promote the neural differentiation of bone marrow derived mesenchymal stem cells ( Xu et al, 2021 ). In addition, the targeting specificity of plant-derived EVs can also be improved by modifying their surface.…”

“…By transferring key miRNAs, exosomes from the neuron, astrocyte, and neural progenitor cell exhibited significant efficiency in promoting neurogenesis ( Takeda and Xu 2015 ; You et al, 2020 ; Yuan et al, 2021 ). Xu et al systematically identified the miRNAs of exosomes from the juice of ginseng by transcriptomic technology, and found 44 kinds of miRNAs perfectly match to the ginseng genome database ( Xu et al, 2021 ). Epigenetics covers heritable phenotype changes that are not involved in alterations of the DNA sequence, which is associated with DD reported by numerous studies ( Yeshurun and Hannan 2019 ; Wheater et al, 2020 ; Xu et al, 2020 ).…”

MiR‐26a‐tetrahedral framework nucleic acids mediated osteogenesis of adipose‐derived mesenchymal stem cells

“…Micro‐RNAs (miRNAs) attract substantial research attention given that they play important roles in cell differentiation, biological development, and disease pathogenesis 1 . Further researches use advanced high‐throughput technology like miRNA microarrays to study the relationship between miRNAs and disease, and conduct in‐depth discussions on the mechanism of miRNAs, making miRNAs expected to become new and promising targets in tissue engineering research 2,3 . miRNAs are a class of small noncoding RNA sequences that act as efficient molecular managers, regulating multiple endogenous processes simultaneously.…”

“… 1 Further researches use advanced high‐throughput technology like miRNA microarrays to study the relationship between miRNAs and disease, and conduct in‐depth discussions on the mechanism of miRNAs, making miRNAs expected to become new and promising targets in tissue engineering research. 2 , 3 miRNAs are a class of small noncoding RNA sequences that act as efficient molecular managers, regulating multiple endogenous processes simultaneously. miRNAs can regulate protein‐coding gene expression, translation process and various biological behaviors of normal or inflammatory cells at multiple levels.…”