Apoptotic extracellular vesicles from peripancreatic adipose-derived mesenchymal stem cells ameliorate severe acute pancreatitis through the transcription factor EB-mediated autophagy-lysosomal pathway: an experimental s

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Background Mesenchymal stem cells (MSCs) and their extracellular vesicles (EVs) have remarkable potential in alleviating the severity of pancreatic inflammation. However, most transplanted MSCs undergo apoptosis shortly after in vivo administration, producing apoptotic EVs (ApoEVs). Our study investigated the potential role and molecular mechanisms of ApoEVs derived from apoptotic MSCs in ameliorating severe acute pancreatitis (SAP). Methods DiO-labeled peripancreatic adipose-derived stem cells (P-ADSCs) were administered to rats with SAP to monitor P-ADSC apoptosis. ApoEVs were isolated from P-ADSCs subjected to apoptosis induction, and conventional EVs were obtained from untreated P-ADSCs. The morphology, size distribution and marker protein expression of ApoEVs and EVs were characterized, and functional differences were assessed via transcriptomic and proteomic analyses to compare their gene and protein compositions. The rat pancreatic acinar cell (PAC) line AR42J was used to assess cellular responses to ApoEVs, and an SAP rat model was used to compare the therapeutic efficacy of ApoEVs in ameliorating SAP. Specific inhibitors and small interfering RNA were used to perform loss-of-function assays. Results P-ADSCs underwent apoptosis in the pancreas within 72 h after being injected into rats with SAP. Notably, ApoEVs exhibited superior therapeutic effects in ameliorating SAP

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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