Exosomes from hypoxic ADSCs ameliorate neuronal damage post spinal cord injury through circ-Wdfy3 delivery and inhibition of ferroptosis

Spinal cord injury (SCI) is severe traumatic damage to the spinal cord, which is often incurable (Ahuja et al.,2017, Furlan et al.,2011). SCI patients suffer both physical and psychological pain. Furthermore, the increasing incidence of SCI places a great burden on society (Fan et al.,2018). A number of studies have reported trials using adipose-derived mesenchymal stem cells (ADSCs), umbilical cord-derived MSCs (UC-MSCs) and bone marrow-derived MSCs (BMSCs) for the treatment of SCI (Liau et al.,2020, Ruzicka et al.,2017, Lim et al.,2016). Previous studies have reported that lncRNA-Gm37494 in exosomes derived from ADSCs (Exos) repaired SCI through microglial M1/M2 polarization (Shao et al.,2020). In addition, ADSC transplantation has been found to alleviate SCI-induced neuroinflammation, partially through suppression of the Jagged1/Notch signaling pathway (Zhou et al.,2020). Furthermore, a recent study highlighted the indispensable role of Exos in regulating the microenvironment (Liang et al.,2022).

Exosomes are extracellular vesicles that range between 50-140 nm in size and are generally released during pathological processes (Ren et al.,2019). Exosomes mediate intercellular connections through the delivery of non-coding RNAs (ncRNAs) including circular RNAs (circRNAs) and microRNAs (miRNAs) and proteins (An et al.,2021, Gao et al.,2021). Since circRNAs regulate gene expression, they are excellent candidates for therapeutic and diagnostic markers. Unlike linear RNA, circRNA 5' and 3' ends are covalently linked to form a circular frame, which makes them resistant to RNA exonuclease degradation, and subsequently more stable than linear RNA (Shi et al.,2020). circRNAs have been implicated in a range of neurological diseases and pathological injuries such as SCI (Li et al.,2021, Zhang et al.,2019). However, the role of circRNAs in SCI have not been fully elucidated. Here, we confirm a therapeutic role for ADSC-Exos in spinal cord repair post-injury through the delivery of circRNAs.

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