Umbilical Cord Derived Mesenchymal Stem Cells Exosomes(Wuhan Union Hospital)

Background:Fibrosis and inflammation due to ureteropelvic junction obstruction substantially contributes to poor renal function. Urine-derived stem-cell-derived exosomes (USC-Exos) have therapeutic effects through paracrine.Methods:In vitro, the effects of USC-Exos on the biological functions of HK-2 and human umbilical vein endothelial cells were tested. Cell inflammation and fibrosis were induced by transforming growth factor-β1 and interleukin-1β, and their anti-inflammatory and antifibrotic effects were observed after exogenous addition of USC-Exos. Through high-throughput sequencing of microRNA in USC-Exos, the pathways and key microRNAs were selected. Then, the antifibrotic and anti-inflammatory effects of exosomal miR-122-5p and target genes were verified. The role of the miR-122-5p/SOX2 axis in anti-inflammatory and antifibrotic effects was verified. In vivo, a rabbit model of partial unilateral ureteral obstruction (PUUO) was established. Magnetic resonance imaging recorded the volume of the renal pelvis after modeling, and renal tissue was pathologically analyzed.Results:We examined the role of USC-Exos and their miR-122-5p content in obstructive kidney injury. These Exos exhibit antifibrotic and anti-inflammatory activities. SOX2 is the hub gene in PUUO and negatively related to renal function. We confirmed the binding relationship between miR-122-5p and SOX2. The anti-inflammatory and antifibrotic effects of miR-122-5p were inhibited, indicating that miR-122-5p has anti-inflammatory and antifibrotic effects by inhibiting SOX2 expression. In vivo, the PUUO group showed typical obstructive kidney injury after modeling. After USC-Exo treatment, the shape of the renal pelvis shown a remarkable improvement, and inflammation and fibrosis decreased.Conclusions:We confirmed that miR-122-5p from USC-Exos targeting SOX2 is a new molecular target for postoperative recovery treatment of obstructive kidney injury.

Osteoarthritis (OA) is a degenerative joint disorder that is distinguished by inflammation and chronic cartilage damage. Interleukin-1β (IL-1β) is a proinflammatory cytokine that plays an important role in the catabolic processes that underlie the pathogenesis of OA. In this study, we investigate the therapeutic efficacy of exosomes derived from untreated bone-marrow-derived mesenchymal stem cells (BMMSC-Exo) and those treated with cinnamaldehyde (BMMSC-CA-Exo) for preventing the in vitro catabolic effects of IL-1β on chondrocytes. We stimulated chondrocytes with IL-1β to mimic the inflammatory microenvironment of OA. We then treated these chondrocytes with BMMSC-Exo and BMMSC-CA-Exo isolated via an aqueous two-phase system and evaluated their effects on the key cellular processes using molecular techniques. Our findings revealed that treatment with BMMSC-Exo reduces the catabolic effects of IL-1β on chondrocytes and alleviates inflammation. However, further studies directly comparing treatments with BMMSC-Exo and BMMSC-CA-Exo are needed to determine if CA preconditioning can provide additional anti-inflammatory benefits to the exosomes beyond those of CA preconditioning or treatment with regular BMMSC-Exo. Through a comprehensive molecular analysis, we elucidated the regulatory mechanisms underlying this protective effect. We found a significant downregulation of proinflammatory signaling pathways in exosome-infected chondrocytes, suggesting the potential modulation of the NF-κB and MAPK signaling cascades. Furthermore, our study identified the molecular cargo of BMMSC-Exo and BMMSC-CA-Exo, determining the key molecules, such as anti-inflammatory cytokines and cartilage-associated factors, that may contribute to their acquisition of chondroprotective properties. In summary, BMMSC-Exo and BMMSC-CA-Exo exhibit the potential as therapeutic agents for OA by antagonizing the in vitro catabolic effects of IL-1β on chondrocytes. The regulation of the proinflammatory signaling pathways and bioactive molecules delivered by the exosomes suggests a multifaceted mechanism of action. These findings highlight the need for further investigation into exosome-based therapies for OA and joint-related diseases.