Bone mesenchymal stem cells for gene transfer of NGF to the adult rat brain: Rescue the NGFR p75 positive neurons from fimbria–fornix lesion-induced degeneration

Leng, Shuilong; Johnsen, Hans Erik; Fan, Wenguo; Cheng, Shaowu; Long, Dahong; He, Hongwen

doi:10.1016/j.neulet.2008.10.016

Cited by 4 publications

(1 citation statement)

References 19 publications

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“…Previous studies have reported that the therapeutic effects of BMSCs were a result of their differentiation potential; however, reports have increasingly suggested that the functions of BMSCs might be attributable to potent paracrine activities such as cytoprotective factors and exosomes (15,32,35,36). A series of cytoprotective factors secreted by BMSCs have been demonstrated to play the important mediatory function of BMSCs (37)(38)(39)(40). However, according to the established paracrine-mediated mechanism, BMexos are considered to represent a new type of intercellular communication and have been further described as a medium composed of proteins, lipids, mRNAs, and miRNAs.…”

Section: Discussionmentioning

confidence: 99%

BMSCs protect against renal ischemia‐reperfusion injury by secreting exosomes loaded with miR‐199a‐5p that target BIP to inhibit endoplasmic reticulum stress at the very early reperfusion stages

Wang

Zhu

et al. 2019

FASEB j.

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Bone marrow–derived mesenchymal stem cells (BMSCs) have been recently reported to play a variety of vital roles in organ and tissue damage repair, mainly via potent paracrine activity, including secreting extracellular vesicles, such as exosomes, that serve as mediators facilitating intercellular communication and reprogramming recipient cells by delivering their contents to target cells. However, the underlying mechanisms are diverse and complex, and the influencing characteristics have rarely been studied. Accordingly, we designed this study to explore the time dependence of the effects of exosomes derived from BMSCs (BMexos) on renal ischemia‐reperfusion (I/R) injury and the underlying mechanisms associated with the reperfusion time. Impressively, our study is the first to find that BMexos protected against renal I/R injury in vitro and in vivo at the very early reperfusion stages, especially 4–8 h after reperfusion in vitro and 8–16 h after reperfusion in vivo. Interestingly, we simultaneously found that endoplasmic reticulum (ER) stress was significantly suppressed following the administration of BMexos in vitro and in vivo with a similar time dependence. Additionally, we discovered that miR‐199a‐5p, which was abundant in the BMSCs, was transferred into renal tubular epithelial cells (NRK‐52E) in a time‐dependent manner and significantly inhibited I/R‐induced ER stress by targeting binding immunoglobulin protein (BIP). Cocultivation with miR‐199a‐5p‐overexpressing BMSCs amplified the suppression of ER stress and further protected against I/R injury. However, coculture with miR‐199a‐5p‐knockdown BMSCs obviously increased ER stress and reversed the BMexos‐induced protection, and silencing BIP by small interfering RNA–1098 in NRK‐52E inhibited these effects. This study provides evidence that administering BMexos at the very early reperfusion stages significantly protects against renal I/R injury, and ER stress is closely linked to this protection. These results suggest a novel therapeutic strategy during the very early reperfusion stages of renal I/R injury.—Wang, C., Zhu, G., He, W., Yin, H., Lin, F., Gou, X., Li, X. BMSCs protect against renal ischemia‐reperfusion injury by secreting exosomes loaded with miR‐199a‐5p that target BIP to inhibit endoplasmic reticulum stress at the very early reperfusion stages. FASEB J. 33, 5440–5456 (2019). http://www.fasebj.org

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