Exosomes released from neural progenitor cells and induced neural progenitor cells regulate neurogenesis through miR-21a

Abstract

Neural stem/progenitor cells (NPCs) are known to have potent therapeutic effects in neurological disorders through secreting exosomes. The limited numbers of NPCs in adult brain and the decline of NPC pool in many neurological disorders restrain the further use of exosomes in treating these diseases. The direct conversion of somatic cells into induced NPCs (iNPCs) provides abundant NPC-like cells to study the therapeutic effects of NPCs-originated exosomes (EXOs). Our recent study demonstrated that iNPCs-derived exosomes (iEXOs) exhibit distinct potential in facilitating the proliferation of NPCs, compared to EXOs, indicating the importance to investigate the effects of EXOs and iEXOs on the differentiation of NPCs, which remains unknown. Here, our results suggest that EXOs, but not iEXOs, promoted neuronal differentiation and neither of them had effect on glial generation. Microarray analysis revealed different miRNA signatures in EXOs and iEXOs, in which miR-21a was highly enriched in EXOs. Perturbation of function assay demonstrated the key roles of miR-21a in the generation of neurons and mediating the neurogenic potential of exosomes. Our data suggest that EXOs and iEXOs may achieve their therapeutic effects in promoting neurogenesis through transferring key miRNAs, which sheds light on the development of highly efficient cell-free therapeutic strategies for treating neurological diseases. Electronic supplementary material The online version of this article (10.1186/s12964-019-0418-3) contains supplementary material, which is available to authorized users.

The microRNA-17 ~ 92 Family as a Key Regulator of Neurogenesis and Potential Regenerative Therapeutics of Neurological Disorders

“…Thus, multiple synthetic or natural nanocarriers have been applied in miR-17~92 delivery, including aforementioned exosomes. Emerging evidence has implicated exosomes as an excellent natural platform for delivering miRNA into the CNS due to superior miRNAs preservation from the RNases, promising targeting capacity post equipping with homing molecules, ability to penetrate the BBB, low-or non-immunogenicity, and flexibility in administration routes [74][75][76][77][78]. These unparalleled characteristics make exosome-based miRNA delivery an interesting and important direction for the development of novel therapeutic strategies for treating neurological disorders.…”

RNAs on the Go: Extracellular Transfer in Insects with Promising Prospects for Pest Management

“…In animals, extracellular RNAs are extensively described in mammalian biofluids. These molecules are known to be secreted followed by functional uptake into recipient cells [ 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 ]. In invertebrates, the presence of extracellular RNAs has been demonstrated in arthropods and nematodes, with a limited number of studies demonstrating functional RNA transfer [ 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 ].…”

Extracellular Vesicles as Innovative Tool for Diagnosis, Regeneration and Protection against Neurological Damage

“…Interestingly, the method of obtaining stem cells influences the types of exosomes they secrete. Thus Ma et al [ 141 ] showed that induced exosomes (iEXOs) secreted from induced neural progenitor cells (iNPCs) stimulated the proliferation of neural progenitor cells (NPCs), as opposed to exosomes secreted by NPCs, which only possess a differentiating ability. This effect was mediated by miR-21, which is highly expressed in NPCs and in later stages of brain development [ 141 ].…”