Mesenchymal stem cell and exosome-based therapy for liver diseases: can it overcome conventional therapeutic inconsistencies?
Liver inflammation, injury, and hepatic cell death are caused by external agents (viruses, bacteria, drugs, alcohol, etc.) along with the genetic susceptibility of an individual. Persistent activation of the fibrogenic response in cells leads to liver fibrosis which in turn progresses to cirrhosis a...
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Open Exploration Publishing Inc.
2025-01-01
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| Series: | Exploration of Digestive Diseases |
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| Online Access: | https://www.explorationpub.com/uploads/Article/A100563/100563.pdf |
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| author | Zahid Hussain |
| author_facet | Zahid Hussain |
| author_sort | Zahid Hussain |
| collection | DOAJ |
| description | Liver inflammation, injury, and hepatic cell death are caused by external agents (viruses, bacteria, drugs, alcohol, etc.) along with the genetic susceptibility of an individual. Persistent activation of the fibrogenic response in cells leads to liver fibrosis which in turn progresses to cirrhosis and cancer. The dysregulation of the immune system generates reactive oxygen species which in turn induce necrosis of hepatocytes. This process activates hepatic stellate cells and myofibroblasts to produce a huge quantity of collagens, alpha-smooth muscle actin, and extracellular matrix deposition in liver parenchyma. Due to the multifactorial nature of this disease, conventional therapies increasingly attempted combinatorial therapy or polytherapy to target multiple mechanistic sites in order to prevent entry into further complicated irreversible stages. Despite advancements in conventional therapy, several cases aggravate fibrosis (grade 3 to 4) and cirrhosis. The inconsistency in treatment outcomes and limited organ donors for liver transplantation have led to an ever-increasing and challenging demand for alternative therapies. In this review, we analyze the mechanism and causative factors of liver diseases, conventional mode, and alternative therapeutic options. The central to liver diseases are immune dysregulation, hence bioactive agents with immunomodulatory properties should be searched and exploited to meet therapeutic needs. Mesenchymal stem cells (MSCs) with their specialized anti-inflammatory and immunomodulatory properties could be utilized as an effective alternative therapeutic candidate in treating inflammatory liver diseases. MSC-derived exosome further provides an additional immunomodulatory option that could work in tandem with MSC in a synergistic form. In this series, we have reviewed preconditioned and genetically edited MSCs to augment homing, proliferation, and differentiation. Importantly, all the clinical challenges should be noted and addressed before stem cell cytotherapy should be considered safe and effective for patients with liver diseases. Published literature indicated that MSC therapy has the potential to substitute conventional options in the treatment of high-grade fibrosis and cirrhosis. |
| format | Article |
| id | doaj-art-3d1bd944454d45c2ac7f90063987ee11 |
| institution | Kabale University |
| issn | 2833-6321 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Open Exploration Publishing Inc. |
| record_format | Article |
| series | Exploration of Digestive Diseases |
| spelling | doaj-art-3d1bd944454d45c2ac7f90063987ee112025-01-17T08:15:10ZengOpen Exploration Publishing Inc.Exploration of Digestive Diseases2833-63212025-01-01410056310.37349/edd.2025.100563Mesenchymal stem cell and exosome-based therapy for liver diseases: can it overcome conventional therapeutic inconsistencies?Zahid Hussain0https://orcid.org/0000-0002-1076-9484Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 135-720, Korea; CG Bhakta Institute of Biotechnology, Uka Tarsadia University, Surat 394350, Gujarat, IndiaLiver inflammation, injury, and hepatic cell death are caused by external agents (viruses, bacteria, drugs, alcohol, etc.) along with the genetic susceptibility of an individual. Persistent activation of the fibrogenic response in cells leads to liver fibrosis which in turn progresses to cirrhosis and cancer. The dysregulation of the immune system generates reactive oxygen species which in turn induce necrosis of hepatocytes. This process activates hepatic stellate cells and myofibroblasts to produce a huge quantity of collagens, alpha-smooth muscle actin, and extracellular matrix deposition in liver parenchyma. Due to the multifactorial nature of this disease, conventional therapies increasingly attempted combinatorial therapy or polytherapy to target multiple mechanistic sites in order to prevent entry into further complicated irreversible stages. Despite advancements in conventional therapy, several cases aggravate fibrosis (grade 3 to 4) and cirrhosis. The inconsistency in treatment outcomes and limited organ donors for liver transplantation have led to an ever-increasing and challenging demand for alternative therapies. In this review, we analyze the mechanism and causative factors of liver diseases, conventional mode, and alternative therapeutic options. The central to liver diseases are immune dysregulation, hence bioactive agents with immunomodulatory properties should be searched and exploited to meet therapeutic needs. Mesenchymal stem cells (MSCs) with their specialized anti-inflammatory and immunomodulatory properties could be utilized as an effective alternative therapeutic candidate in treating inflammatory liver diseases. MSC-derived exosome further provides an additional immunomodulatory option that could work in tandem with MSC in a synergistic form. In this series, we have reviewed preconditioned and genetically edited MSCs to augment homing, proliferation, and differentiation. Importantly, all the clinical challenges should be noted and addressed before stem cell cytotherapy should be considered safe and effective for patients with liver diseases. Published literature indicated that MSC therapy has the potential to substitute conventional options in the treatment of high-grade fibrosis and cirrhosis.https://www.explorationpub.com/uploads/Article/A100563/100563.pdfmesenchymal stem cellexosomehepatic stellate cellcollagenextracellular matrixcell therapyliver fibrosisinflammation |
| spellingShingle | Zahid Hussain Mesenchymal stem cell and exosome-based therapy for liver diseases: can it overcome conventional therapeutic inconsistencies? Exploration of Digestive Diseases mesenchymal stem cell exosome hepatic stellate cell collagen extracellular matrix cell therapy liver fibrosis inflammation |
| title | Mesenchymal stem cell and exosome-based therapy for liver diseases: can it overcome conventional therapeutic inconsistencies? |
| title_full | Mesenchymal stem cell and exosome-based therapy for liver diseases: can it overcome conventional therapeutic inconsistencies? |
| title_fullStr | Mesenchymal stem cell and exosome-based therapy for liver diseases: can it overcome conventional therapeutic inconsistencies? |
| title_full_unstemmed | Mesenchymal stem cell and exosome-based therapy for liver diseases: can it overcome conventional therapeutic inconsistencies? |
| title_short | Mesenchymal stem cell and exosome-based therapy for liver diseases: can it overcome conventional therapeutic inconsistencies? |
| title_sort | mesenchymal stem cell and exosome based therapy for liver diseases can it overcome conventional therapeutic inconsistencies |
| topic | mesenchymal stem cell exosome hepatic stellate cell collagen extracellular matrix cell therapy liver fibrosis inflammation |
| url | https://www.explorationpub.com/uploads/Article/A100563/100563.pdf |
| work_keys_str_mv | AT zahidhussain mesenchymalstemcellandexosomebasedtherapyforliverdiseasescanitovercomeconventionaltherapeuticinconsistencies |