MiR-17-92 enriched exosomes derived from multipotent mesenchymal stromal cells enhance axon-myelin remodeling and motor electrophysiological recovery after stroke

Abstract

MiR-17-92 cluster enriched exosomes derived from multipotent mesenchymal stromal cells (MSCs) increase functional recovery after stroke. Here, we investigate the mechanisms underlying this recovery. At 24 h (h) post transient middle cerebral artery occlusion, rats received control liposomes or exosomes derived from MSCs infected with pre-miR-17-92 expression lentivirus (Exo-miR-17-92+) or control lentivirus (Exo-Con) intravenously. Compared to the liposomes, exosomes significantly reduced the intracortical microstimulation threshold current of the contralateral cortex for evoking impaired forelimb movements (day 21), increased the neurite and myelin density in the ischemic boundary area, and contralesional axonal sprouting into the caudal forelimb area of ipsilateral side and in the denervated spinal cord (day 28), respectively. The Exo-miR-17-92+ further enhanced axon-myelin remodeling and electrophysiological recovery compared with the EXO-Con. Ex vivo cultured rat brain slice data showed that myelin and neuronal fiber density were significantly increased by Exo-miR-17-92+, while significantly inhibited by application of the PI3K/Akt/mTOR pathway inhibitors. Our studies suggest that the miR-17-92 cluster enriched MSC exosomes enhanced neuro-functional recovery of stroke may be attributed to an increase of axonal extension and myelination, and this enhanced axon-myelin remodeling may be mediated in part via the activation of the PI3K/Akt/mTOR pathway induced by the downregulation of PTEN.

Exosomes containing miR‐451a is involved in the protective effect of cerebral ischemic preconditioning against cerebral ischemia and reperfusion injury

“…Exosomes are extracellular vesicles that transport proteins, miRNAs, lncRNAs, and circRNAs to remotely regulate physiological and pathological processes 14 . Studies show that exosomes derived from endothelial progenitor cells, adipose‐derived stem cells, and multipotent mesenchymal stromal cells can manifest neuroprotective or neurotrophic effects by transporting protective miRNAs 23‐25 . Consistent with this, the plasma exosomes of sham‐operated and cerebral‐IPC mice in our study showed distinct miRNA profiles.…”

Electroacupuncture facilitates the integration of a grafted TrkC‐modified mesenchymal stem cell‐derived neural network into transected spinal cord in rats via increasing neurotrophin‐3

“…Further studies are clearly desirable to decipher the underlying mechanisms. Besides the neurotrophin and immune regulation, 41 emerging evidence has shown that MSC transplantion can protect and improve the neuron function after injury via exosomes 42 and mitochondrial transfer 43 . Notwithstanding of the above, it is suggested that MN+EA treatment as demonstrated in the present study can repair the SCI effectively which is likely through multiple effects.…”

Intravenously delivered multilineage-differentiating stress enduring cells dampen excessive glutamate metabolism and microglial activation in experimental perinatal hypoxic ischemic encephalopathy

“…Mesenchymal stem cells (MSCs) pose as a potential source for transplantable cells as evidenced by their therapeutic effects in rat and mouse HIE models. 10 The postulated mechanism of MSCs implicates trophic effects delivered by cytokines and nutritional factors, 11,12 but the transplanted cells display only transient engraftment into the host tissue, thereby preventing long-term therapeutic effects. 13 Multilineage-differentiating stress enduring cells (Muse cells), harvested from bone marrow (BM), blood and organ connective tissues, display endogenous pluripotent-like property and express pluripotent surface marker stage-specific embryonic antigen-3 (SSEA-3).…”