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Background: Human umbilical cord blood mesenchymal stem cells (HUCB‐MSCs) can exert a protective effect in rat models of acute liver failure (ALF). Vascular endothelial growth factor 165 (VEGF165) is the predominant VEGF isoform and possesses a strong pro‐angiogenic function. In the present study, HUCB‐MSC served as the gene delivery vehicle for the VEGF165 gene, and we explored the therapeutic effects of this system on ALF. Methods: HUCB‐MSCs were infected with an adenovirus expressing green fluorescent protein (GFP)‐VEFG fusion protein (Ad‐VEGF165) to overexpress VEGF165 or an adenovirus expressing GFP (Ad‐GFP) as control. The control and modified HUCB‐MSCs were then transplanted into ALF model rats. Liver function and liver pathological changes were assessed by biochemical tests and liver histology. Immunohistochemistry was carried out to determine the expression of, CD34, Ki67 and VEGF. Results: VEGF165 overexpression enhanced the multipotency of HUCB‐MSCs and promoted the homing and colonization of HUCB‐MSC in the liver tissues of ALF rats. Furthermore, although HUCB‐MSC transplantation ameliorated liver damage and promoted liver regeneration to some extent in ALF rats, Ad‐VEGF165‐HUCB‐MSC transplantation showed stronger therapeutic effects on ALF. Conclusions: In summary, transplantation of VEGF165‐modified HUCB‐MSCs exert stronger therapeutic effects on ALF than HUCB‐MSCs. The present study provides a novel therapeutic approach for ALF. [ABSTRACT FROM AUTHOR]

Peroxisome dynamics are crucial for intestinal stem cell (ISC) differentiation and gut regeneration. However, the precise mechanisms that govern peroxisome dynamics within ISCs during gut regeneration remain unknown. Using mouse colitis and Drosophila intestine models, we have identified a negative-feedback control mechanism involving the transcription factors peroxisome proliferator-activated receptors (PPARs) and SOX21. This feedback mechanism effectively regulates peroxisome abundance during gut regeneration. Following gut injury, the released free very long-chain fatty acids (VLCFAs) increase peroxisome abundance by stimulating PPARs-PEX11s signaling. PPARs act to stimulate peroxisome fission and inhibit pexophagy. SOX21, which acts downstream of peroxisomes during ISC differentiation, induces peroxisome elimination through pexophagy while repressing PPAR expression. Hence, PPARs and SOX21 constitute a finely tuned negative-feedback loop that regulates peroxisome dynamics. These findings shed light on the complex molecular mechanisms underlying peroxisome regulation in ISCs, contributing to our understanding of gut renewal and repair., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Human umbilical cord blood mesenchymal stem cells (HUCB-MSCs) can exert a protective effect in rat models of acute liver failure (ALF). Vascular endothelial growth factor 165 (VEGF 165 ) is the predominant VEGF isoform and possesses a strong pro-angiogenic function. In the present study, HUCB-MSC served as the gene delivery vehicle for the VEGF 165 gene, and we explored the therapeutic effects of this system on ALF., Methods: HUCB-MSCs were infected with an adenovirus expressing green fluorescent protein (GFP)-VEFG fusion protein (Ad-VEGF 165 ) to overexpress VEGF 165 or an adenovirus expressing GFP (Ad-GFP) as control. The control and modified HUCB-MSCs were then transplanted into ALF model rats. Liver function and liver pathological changes were assessed by biochemical tests and liver histology. Immunohistochemistry was carried out to determine the expression of, CD34, Ki67 and VEGF., Results: VEGF 165 overexpression enhanced the multipotency of HUCB-MSCs and promoted the homing and colonization of HUCB-MSC in the liver tissues of ALF rats. Furthermore, although HUCB-MSC transplantation ameliorated liver damage and promoted liver regeneration to some extent in ALF rats, Ad-VEGF 165 -HUCB-MSC transplantation showed stronger therapeutic effects on ALF., Conclusions: In summary, transplantation of VEGF 165 -modified HUCB-MSCs exert stronger therapeutic effects on ALF than HUCB-MSCs. The present study provides a novel therapeutic approach for ALF., (© 2021 John Wiley & Sons, Ltd.)