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Effectiveness of human adipose tissue-derived mesenchymal stem cells expressing alpha-1 antitrypsin gene in liver fibrosis: a study in mice.
Ali Hosseinzadeh, Sara; Sahebghadam Lotfi, Abbas; Davoodian, Nahid; Arjmand, Sareh; Rangchi, Marjan; Mashhadiabbas, Fatemeh.
Afiliación
  • Ali Hosseinzadeh S; Department of Clinical Biochemistry, Faculty of Medical Science, Tarbiat Modares University, Tehran, Iran.
  • Sahebghadam Lotfi A; Department of Clinical Biochemistry, Faculty of Medical Science, Tarbiat Modares University, Tehran, Iran.
  • Davoodian N; Endocrinology and Metabolism Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
  • Arjmand S; Department of Clinical Biochemistry, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
  • Rangchi M; Protein Research Center, Shahid Beheshti University, Tehran, Iran.
  • Mashhadiabbas F; Department of Clinical Biochemistry, Faculty of Medical Science, Tarbiat Modares University, Tehran, Iran.
Gastroenterol Hepatol Bed Bench ; 17(2): 151-160, 2024.
Article en En | MEDLINE | ID: mdl-38994502
ABSTRACT

Aim:

The present study examined the protective potential of human adipose tissue-derived mesenchymal stem cells (hASCs) modified to overexpress alpha-1 antitrypsin (AAT), in a mouse model of the liver fibrosis.

Background:

For the treatment of end-stage liver diseases, cell therapy has emerged as a promising noninvasive alternative to liver transplantation. Mesenchymal stem cells (MSCs) are being evaluated due to their dual capabilities of promoting liver regeneration and modulating the pathogenic inflammation of the immune system.

Methods:

Liver fibrosis was induced in mice via the intraperitoneal injection of carbon tetrachloride (CCl4). MSCs were extracted from the human adipose tissue. After stemness confirmation, the cells were transduced with the lentiviruses containing the AAT gene, and then injected into the mice's tail vein. Fourteen days' post-transplantation, mice were sacrificed, and blood and tissue samples were collected for analysis. Important liver enzymes, including alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), albumin, and total bilirubin (TB), were measured. Histological studies were carried out using the hematoxylin and eosin (H&E), as well as Masson's trichrome (MT) staining.

Results:

Compared to hASCs, treatment with AAT-hASCs resulted in greater reductions in ALT, AST, ALP, and TB, as well as normalized albumin levels. AAT-hASCs promoted enhanced liver regeneration histologically, likely attributable to anti-inflammatory and anti-proteolytic properties of AAT.

Conclusion:

These findings indicate AAT-engineered hASCs as a promising cell-gene therapy candidate for further study in liver cirrhosis models.
Palabras clave

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Gastroenterol Hepatol Bed Bench Año: 2024 Tipo del documento: Article País de afiliación: Irán Pais de publicación: Irán

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Gastroenterol Hepatol Bed Bench Año: 2024 Tipo del documento: Article País de afiliación: Irán Pais de publicación: Irán