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He JL, You YX, Pei X, Jiang W, Zeng QM, Chen B, Wang YH, Chen EQ, Tang H, Gao XF, Wu DB. Tracking of Stem Cells in Chronic Liver Diseases: Current Trends and Developments. Stem Cell Rev Rep 2024; 20:447-454. [PMID: 37993759 DOI: 10.1007/s12015-023-10659-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/15/2023] [Indexed: 11/24/2023]
Abstract
Stem cell therapy holds great promise for future clinical practice for treatment of advanced liver diseases. However, the fate of stem cells after transplantation, including the distribution, viability, and the cell clearance, has not been fully elucidated. Herein, recent advances regarding the imaging tools for stem cells tracking mainly in chronic liver diseases with the advantages and disadvantages of each approach have been described. Magnetic resonance imaging is a promising clinical imaging modality due to non-radioactivity, excellent penetrability, and high spatial resolution. Fluorescence imaging and radionuclide imaging demonstrate relatively increased sensitivity, with the latter excelling in real-time monitoring. Reporter genes specialize in long-term tracing. Nevertheless, the disadvantages of low sensitivity, radiation, exogenous gene risk are inevitably present in each of these means, respectively. In this review, we aim to comprehensively evaluate the current state of methods for tracking of stem cell, highlighting their strengths and weaknesses, and providing insights into their future potential. Multimodality imaging strategies may overcome the inherent limitations of single-modality imaging by combining the strengths of different imaging techniques to provide more comprehensive information in the clinical setting.
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Affiliation(s)
- Jin-Long He
- West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, 610065, China
| | - Yi-Xian You
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Xiong Pei
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Wei Jiang
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Qing-Min Zeng
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Bin Chen
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Yong-Hong Wang
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - En-Qiang Chen
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Hong Tang
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Xiu-Feng Gao
- West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, 610065, China.
| | - Dong-Bo Wu
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China.
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Ma JF, Gao JP, Shao ZW. Acute liver failure: A systematic review and network meta-analysis of optimal type of stem cells in animal models. World J Stem Cells 2023; 15:1-15. [PMID: 36713788 PMCID: PMC9850664 DOI: 10.4252/wjsc.v15.i1.1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Revised: 11/23/2022] [Accepted: 12/23/2022] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND The therapeutic effects of various stem cells in acute liver failure (ALF) have been demonstrated in preclinical studies. However, the specific type of stem cells with the highest therapeutic potential has not been determined.
AIM To validate the efficacy of stem cells in ALF model and to identify the most promising stem cells.
METHODS A search was conducted on the PubMed, Web of Science, Embase, Scopus, and Cochrane databases from inception to May 3, 2022, and updated on November 16, 2022 to identify relevant studies. Two independent reviewers performed the literature search, identification, screening, quality assessment, and data extraction.
RESULTS A total of 89 animal studies were included in the analysis. The results of traditional meta-analysis showed that stem cell therapy could significantly reduce the serum levels of alanine aminotransferase [weighted mean difference (WMD) = -181.05 (-191.71, -170.39)], aspartate aminotransferase [WMD = -309.04 (-328.45, -289.63)], tumor necrosis factor-alpha [WMD = -8.75 (-9.93, -7.56)], and interleukin-6 [WMD = -10.43 (-12.11, -8.76)] in animal models of ALF. Further subgroup analysis and network meta-analysis showed that although mesenchymal stem cells are the current research hotspot, the effect of liver stem cells (LSCs) on improving liver function is significantly better than that of the other five types of stem cells. In addition, the ranking results showed that the possibility of LSCs improving liver function ranked first. This fully proves the great therapeutic potential of LSCs, which needs to be paid more attention in the future.
CONCLUSION LSCs may have a higher therapeutic potential. Further high-quality animal experiments are needed to explore the most effective stem cells for ALF.
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Affiliation(s)
- Jun-Feng Ma
- Department of Surgical Oncology, Gansu Provincial Hospital, Lanzhou 730030, Gansu Province, China
| | - Jian-Ping Gao
- Department of Surgical Oncology, Gansu Provincial Hospital, Lanzhou 730030, Gansu Province, China
| | - Zi-Wei Shao
- Department of Surgical Oncology, Gansu Provincial Hospital, Lanzhou 730030, Gansu Province, China
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3
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Abo-Aziza FAM, Zaki AKA, Adel RM, Fotouh A. Amelioration of aflatoxin acute hepatitis rat model by bone marrow mesenchymal stem cells and their hepatogenic differentiation. Vet World 2022; 15:1347-1364. [PMID: 35765490 PMCID: PMC9210847 DOI: 10.14202/vetworld.2022.1347-1364] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Accepted: 04/18/2022] [Indexed: 11/16/2022] Open
Abstract
Background and Aim: Bone marrow-derived mesenchymal stem cells (BM-MSCs) transplantation and their hepatogenic differentiated cells (HDCs) can be applied for liver injury repair by tissue grafting. Regenerative potentiality in liver cirrhosis models was widely investigated; however, immunomodulation and anti-inflammation in acute hepatitis remain unexplored. This study aimed to explore the immunomodulatory and evaluate twice intravenous (IV) or intrahepatic (IH) administration of either BM-MSCs or middle-stage HDCs on aflatoxin (AF) acute hepatitis rat model. Materials and Methods: BM-MSCs viability, phenotypes, and proliferation were evaluated. Hepatogenic differentiation, albumin, and mmmmmmmm-fetoprotein gene expression were assessed. AF acute hepatitis was induced in rats using AFB1 supplementation. The transplantation of BM-MSCs or their HDCs was done either by IV or IH route. Hepatic ultrasound was performed after 3-weeks of therapy. Cytokines profile (tumor necrosis factor-α [TNF-α], interleukin [IL]-4, and IL-10) was assessed. Hepatic bio-indices, serum, and hepatic antioxidant activity were evaluated, besides examining liver histological sections. Results: Acute AFB1 showed a significant increase in TNF-α (p<0.01), liver enzyme activities (p<0.05), as well as decrease in IL-4, IL-10, and antioxidant enzyme activities (p<0.05). Cytokines profile was ameliorated in groups treated with IV and IH BM-MCs, showed a negative correlation between IL-4 and TNF-α (p<0.05), and a positive correlation between IL-10 upregulation and TNF-α (p<0.01). In IV HDCs treated group, positive correlations between IL-4 and IL-10 downregulation and TNF-α were observed. However, in IH HDCs group, a significant positive correlation between IL-4 and IL-10 upregulation and TNF-α, were recorded (p<0.05). In addition, IV BM-MSCs and IH HDCs treatments significantly increased antioxidant enzymes activity (p<0.05). IV and IH BM-MSCs significantly ameliorated liver transaminase levels, whereas IH HDCs significantly ameliorated alanine aminotransferase activity and nitric oxide concentration (p<0.05). Conclusion: The administration routes of BM-MSCs did not demonstrate any significant difference; however, the IH route of HDCs showed significant amelioration from the IV route. On the other hand, it showed noticeable anti-inflammatory and immunomodulatory improvements in aflatoxicosis rats. Therefore, it can be concluded that acute hepatitis can be treated by a noninvasive IV route without the expense of hepatogenic differentiation. Further research using clinical trials that address several problems regarding engraftment and potentiation are needed to determine the optimal manipulation strategy as well as to achieve better long term effects.
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Affiliation(s)
- Faten A. M. Abo-Aziza
- Department of Parasitology and Animal Diseases, Veterinary Research Institute, National Research Centre, Cairo, Egypt
| | - Abdel Kader A. Zaki
- Department of Physiology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt; Department of Veterinary Medicine, College of Agriculture and Veterinary Medicine, Qassim University, Buraydah, Saudi Arabia
| | - Rana M. Adel
- Zoology Department, Faculty of Women for Arts, Science and Education, Ain Shams University, Cairo, Egypt
| | - Ahmed Fotouh
- Department of Pathology and Clinical Pathology, Faculty of Veterinary Medicine, New Valley University, El-Kharga, Egypt
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Hou Y, Ding W, Wu P, Liu C, Ding L, Liu J, Wang X. Adipose-derived stem cells alleviate liver injury induced by type 1 diabetes mellitus by inhibiting mitochondrial stress and attenuating inflammation. Stem Cell Res Ther 2022; 13:132. [PMID: 35365229 PMCID: PMC8973806 DOI: 10.1186/s13287-022-02760-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Accepted: 01/11/2022] [Indexed: 01/30/2023] Open
Abstract
Background Type 1 diabetes mellitus (T1D) is a worldwide health priority due to autoimmune destruction and is associated with an increased risk of multiorgan complications. Among these complications, effective interventions for liver injury, which can progress to liver fibrosis and hepatocellular carcinoma, are lacking. Although stem cell injection has a therapeutic effect on T1D, whether it can cure liver injury and the underlying mechanisms need further investigation. Methods Sprague–Dawley rats with streptozotocin (STZ)-induced T1D were treated with adipose-derived stem cell (ADSC) or PBS via the tail vein formed the ADSC group or STZ group. Body weights and blood glucose levels were examined weekly for 6 weeks. RNA-seq and PCR array were used to detect the difference in gene expression of the livers between groups. Results In this study, we found that ADSCs injection alleviated hepatic oxidative stress and injury and improved liver function in rats with T1D; potential mechanisms included cytokine activity, energy metabolism and immune regulation were potentially involved, as determined by RNA-seq. Moreover, ADSC treatment altered the fibroblast growth factor 21 (FGF21) and transforming growth factor β (TGF-β) levels in T1D rat livers, implying its repair capacity. Disordered intracellular energy metabolism, which is closely related to mitochondrial stress and dysfunction, was inhibited by ADSC treatment. PCR array and ingenuity pathway analyses suggested that the ADSC-induced suppression of mitochondrial stress is related to decreased necroptosis and apoptosis. Moreover, mitochondria-related alterations caused liver inflammation, resulting in liver injury involving the T lymphocyte-mediated immune response. Conclusions Overall, these results improve our understanding of the curative effect of ADSCs on T1D complications: ADSCs attenuate liver injury by inhibiting mitochondrial stress (apoptosis and dysfunctional energy metabolism) and alleviating inflammation (inflammasome expression and immune disorder). These results are important for early intervention in liver injury and for delaying the development of liver lesions in patients with T1D. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-022-02760-z.
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Affiliation(s)
- Yanli Hou
- Endocrine and Metabolic Diseases Hospital of Shandong First Medical University, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Wenyu Ding
- Endocrine and Metabolic Diseases Hospital of Shandong First Medical University, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Peishan Wu
- Endocrine and Metabolic Diseases Hospital of Shandong First Medical University, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.,Shandong First Medical University, Jinan, China
| | - Changqing Liu
- Endocrine and Metabolic Diseases Hospital of Shandong First Medical University, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Lina Ding
- Endocrine and Metabolic Diseases Hospital of Shandong First Medical University, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Junjun Liu
- Endocrine and Metabolic Diseases Hospital of Shandong First Medical University, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Xiaolei Wang
- Endocrine and Metabolic Diseases Hospital of Shandong First Medical University, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
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5
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Prządka P, Buczak K, Frejlich E, Gąsior L, Suliga K, Kiełbowicz Z. The Role of Mesenchymal Stem Cells (MSCs) in Veterinary Medicine and Their Use in Musculoskeletal Disorders. Biomolecules 2021; 11:1141. [PMID: 34439807 PMCID: PMC8391453 DOI: 10.3390/biom11081141] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Revised: 07/27/2021] [Accepted: 07/30/2021] [Indexed: 12/11/2022] Open
Abstract
Regenerative medicine is a dynamically developing field of human and veterinary medicine. The animal model was most commonly used for mesenchymal stem cells (MSCs) treatment in experimental and preclinical studies with a satisfactory therapeutic effect. Year by year, the need for alternative treatments in veterinary medicine is increasing, and other applications for promising MSCs and their biological derivatives are constantly being sought. There is also an increase in demand for other methods of treating disease states, of which the classical treatment methods did not bring the desired results. Cell therapy can be a realistic option for treating human and animal diseases in the near future and therefore additional research is needed to optimize cell origins, numbers, or application methods in order to standardize the treatment process and assess its effects. The aim of the following work was to summarize available knowledge about stem cells in veterinary medicine and their possible application in the treatment of chosen musculoskeletal disorders in dogs and horses.
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Affiliation(s)
- Przemysław Prządka
- Department of Surgery, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Science, Pl. Grunwadzki 51, 50-366 Wroclaw, Poland; (K.B.); (Z.K.)
| | - Krzysztof Buczak
- Department of Surgery, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Science, Pl. Grunwadzki 51, 50-366 Wroclaw, Poland; (K.B.); (Z.K.)
| | - Ewelina Frejlich
- 2nd Department of General Surgery and Surgical Oncology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland;
| | - Ludwika Gąsior
- Vets & Pets Veterinary Clinic, Zakladowa 11N, 50-231 Wroclaw, Poland;
| | - Kamil Suliga
- Student Veterinary Surgical Society “LANCET”, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Science, Pl. Grunwaldzki 51, 50-366 Wroclaw, Poland;
| | - Zdzisław Kiełbowicz
- Department of Surgery, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Science, Pl. Grunwadzki 51, 50-366 Wroclaw, Poland; (K.B.); (Z.K.)
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6
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Luan Y, Kong X, Feng Y. Mesenchymal stem cells therapy for acute liver failure: Recent advances and future perspectives. LIVER RESEARCH 2021; 5:53-61. [PMID: 39959343 PMCID: PMC11791815 DOI: 10.1016/j.livres.2021.03.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Revised: 02/16/2021] [Accepted: 03/24/2021] [Indexed: 12/21/2022]
Abstract
Acute liver failure (ALF) is a life-threatening disease characterized by the rapid development of hepatocyte death and a systemic inflammatory response, which leads to high mortality. Despite the prevention of ALF complications, therapeutic effectiveness remains limited because of the rapid disease progression. Thus, there is a need to explore various therapeutic approaches. Currently, the only effective treatment is liver transplantation; However, the lack of donors, surgical complications, immunosuppression, and high medical costs limit its clinical application. Recently, mesenchymal stem cells (MSCs) have been found to exert hepatoprotective effects in ALF through suppression of inflammation, immunoregulation, promotion of mitosis, anti-apoptosis effects, and alleviation of the metabolic and oxidative stress imbalance. In this review, we summarize the advantages and disadvantages of MSCs from different sources and their molecular mechanisms in ALF treatment, along with future perspectives that may provide guidance to improve the current status of MSCs therapy for ALF.
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Affiliation(s)
- Yuling Luan
- Department of General Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xiaoni Kong
- Central Laboratory, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yu Feng
- Department of General Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
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7
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Chen Q, You Y, Zhang Y, Zhang H, Bai L. Hepatocyte growth factor mediates a novel form of hepatic stem/progenitor cell-induced tolerance in a rat xenogeneic liver rejection model. Int Immunopharmacol 2021; 90:107180. [PMID: 33221167 DOI: 10.1016/j.intimp.2020.107180] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Revised: 11/02/2020] [Accepted: 11/02/2020] [Indexed: 12/17/2022]
Abstract
We have previously identified novel neural/glial antigen 2-expressing hepatic stem/progenitor cells (NG2+ HSPs) that are beneficial for tissue repair by inhibiting the immune cell response. In this in vivo study, we investigated the use of hepatocyte growth factor (HGF)-secreting NG2+ HSPs as a tolerogen in the well-established Syrian golden hamster (SGH) to Lewis (LEW) xenogeneic rat acute liver rejection (ARJ) model. Liver and blood cells were collected for histology and functional analyses using immunofluorescence staining, western blot, ELISA, and TUNEL assays. All recipient rats were randomly divided into 5 groups (n = 14 rats/group) and treated with: (1) ARJ + PBS: (2) ARJ + NG2: tail vein injection of NG2+ HSPs; (3) ARJ + tacrolimus (FK506, oral administration); (4) ARJ + an anti-cMet functional blocking antibody (a-cMet-Ab, I.V) 24 h before the injection of NG2+ HSPs; (5) ARJ + cHGF (clinically used HGF). LEW to LEW syngeneic rats were considered "normal" (n = 14, namely Syn). Significantly prolonged mean survival times (MSTs) and improved graft functions were observed after NG2+ HSP transplantation. An anti-cMet Ab significantly blocked the effect of NG2+ HSPs, suggesting that the effects were likely associated with HGF secreted from NG2+ HSPs. Notably, when intravenously injected into the xenogeneic rat model, the injected cHGF not only prolonged the MST of recipient rats but also increased the number of TUNEL-expressing xenoreactive cytotoxic T lymphocytes (CD8+ T cells). Based on these results, HGF-secreting NG2+ HSPs may specifically target recipient CD8+ T cells by inducing their apoptosis.
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Affiliation(s)
- Quanyu Chen
- Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of Education, Laboratory of Molecular Developmental Biology, School of Life Sciences, Southwest University, Beibei, 400715 Chongqing, China; Hepatobiliary Institute, Southwest Hospital, the Army Medical University, No. 30 Gaotanyan, ShapingBa Distract, Chongqing 400038, China
| | - Yu You
- Department of Hepatobiliary Surgery, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Yujun Zhang
- Hepatobiliary Institute, Southwest Hospital, the Army Medical University, No. 30 Gaotanyan, ShapingBa Distract, Chongqing 400038, China
| | - Hongyu Zhang
- Hepatobiliary Institute, Southwest Hospital, the Army Medical University, No. 30 Gaotanyan, ShapingBa Distract, Chongqing 400038, China.
| | - Lianhua Bai
- Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of Education, Laboratory of Molecular Developmental Biology, School of Life Sciences, Southwest University, Beibei, 400715 Chongqing, China; Hepatobiliary Institute, Southwest Hospital, the Army Medical University, No. 30 Gaotanyan, ShapingBa Distract, Chongqing 400038, China.
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8
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Improvement of mesenchymal stromal cells and their derivatives for treating acute liver failure. J Mol Med (Berl) 2019; 97:1065-1084. [DOI: 10.1007/s00109-019-01804-x] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2018] [Revised: 04/28/2019] [Accepted: 05/23/2019] [Indexed: 02/07/2023]
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9
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Jin Y, Wang J, Li H, Gao S, Shi R, Yang D, Wang X, Wang X, Zhu L, Wang X, Chen C, Ning K, Gao Z, Xu J, Fu Q. Extracellular Vesicles Secreted by Human Adipose-derived Stem Cells (hASCs) Improve Survival Rate of Rats with Acute Liver Failure by Releasing lncRNA H19. EBioMedicine 2018; 34:231-242. [PMID: 30077720 PMCID: PMC6116414 DOI: 10.1016/j.ebiom.2018.07.015] [Citation(s) in RCA: 58] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2017] [Revised: 07/08/2018] [Accepted: 07/12/2018] [Indexed: 02/07/2023] Open
Abstract
It has previously been reported that human adipose-derived stem cells (hASCs) can promote the regeneration of damaged tissues in rats with liver failure through a ‘paracrine effect’. Here we demonstrate a therapeutic effect of hASCs derived Extracellular Vesicles (EVs) on rat models with acute liver failure, as shown by the improvement of the survival rate by >70% compared to controls. Gene sequencing of rat liver revealed an increase in human long-chain non-coding RNA (lncRNA) H19 after hASC-derived EVs transplantation. When the H19 coding sequence was silenced in hASCs and EVs were then collected for treatment of rats with liver failure, we saw a decrease in the survival rate to 40%, compared to treatment with EVs generated from non-silenced hASCs. These data indicate that lncRNA H19 may be a potential therapeutic target for the treatment of liver failure.
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Affiliation(s)
- Yinpeng Jin
- Shanghai Public Health Clinical Center, Fudan University, Jinshan, Shanghai 201508, PR China.
| | - Junyi Wang
- Shanghai Liver Diseases Research Center, The 85th Hospital of PLA, Shanghai 200235, PR China
| | - Hongchao Li
- Shanghai Liver Diseases Research Center, The 85th Hospital of PLA, Shanghai 200235, PR China
| | - Shane Gao
- East Hospital, Tongji University School of Medicine, Shanghai 200120, PR China
| | - Rongfeng Shi
- Department of Interventional & Vascular Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, PR China
| | - Danjing Yang
- East Hospital, Tongji University School of Medicine, Shanghai 200120, PR China
| | - Xianli Wang
- Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, PR China
| | - Xi Wang
- Shanghai Public Health Clinical Center, Fudan University, Jinshan, Shanghai 201508, PR China
| | - Liang Zhu
- East Hospital, Tongji University School of Medicine, Shanghai 200120, PR China
| | - Xiaojin Wang
- Shanghai Liver Diseases Research Center, The 85th Hospital of PLA, Shanghai 200235, PR China
| | - Chengwei Chen
- Shanghai Liver Diseases Research Center, The 85th Hospital of PLA, Shanghai 200235, PR China
| | - Ke Ning
- Department of Neuroscience, Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
| | - Zhengliang Gao
- East Hospital, Tongji University School of Medicine, Shanghai 200120, PR China.
| | - Jun Xu
- East Hospital, Tongji University School of Medicine, Shanghai 200120, PR China.
| | - Qingchun Fu
- Shanghai Public Health Clinical Center, Fudan University, Jinshan, Shanghai 201508, PR China.
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Bartas M, Červeň J, Oppelt J, Peteja M, Vávra P, Zonča P, Procházka V, Brázda V, Pečinka P. Liver regeneration during the associating liver partition and portal vein ligation for staged hepatectomy procedure in Sus scrofa is positively modulated by stem cells. Oncol Lett 2018; 15:6309-6321. [PMID: 29616108 PMCID: PMC5876427 DOI: 10.3892/ol.2018.8108] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2017] [Accepted: 11/02/2017] [Indexed: 11/17/2022] Open
Abstract
This present study investigated the impact of the application of stem cells to liver regeneration following the first stage of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). The experiment was conducted on a pig model (n=6, 3 that did not receive application of stem cells, 3 that received application stem cells). Collected samples of liver (day 0 and 9 following surgery) were subjected to complete transcriptome sequencing. In total, 39 differentially expressed genes were found in the group without the application of the stem cells (genes of unwanted processes such as fibrosis and inflammation). In the group that did receive application of stem cells, no significantly differentially expressed genes were found, indicating a properly regenerated liver remnant. The present study therefore demonstrated, to the best of our knowledge for the first time, the positive effect of stem cells application in the liver regeneration process during ALPPS procedure in the pig model.
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Affiliation(s)
- Martin Bartas
- Department of Biology and Ecology, Faculty of Science, University of Ostrava, 71000 Ostrava, Czech Republic
| | - Jiri Červeň
- Department of Biology and Ecology, Faculty of Science, University of Ostrava, 71000 Ostrava, Czech Republic.,Institute of Environmental Technologies, Faculty of Science, University of Ostrava, 71000 Ostrava, Czech Republic
| | - Jan Oppelt
- Centre for Structural Biology, Central European Institute of Technology, Masaryk University, 62500 Brno, Czech Republic.,National Centre for Biomolecular Research, Centre for Structural Biology, Central European Institute of Technology, Masaryk University, 62500 Brno, 70852 Ostrava, Czech Republic
| | - Matus Peteja
- Department of Surgery, University Hospital in Ostrava, 70852 Ostrava, Czech Republic.,Department of Surgical Studies, Faculty of Medicine, University of Ostrava, 70852 Ostrava, Czech Republic
| | - Petr Vávra
- Department of Surgery, University Hospital in Ostrava, 70852 Ostrava, Czech Republic.,Department of Surgical Studies, Faculty of Medicine, University of Ostrava, 70852 Ostrava, Czech Republic
| | - Pavel Zonča
- Department of Surgery, University Hospital in Ostrava, 70852 Ostrava, Czech Republic.,Department of Surgical Studies, Faculty of Medicine, University of Ostrava, 70852 Ostrava, Czech Republic
| | - Vaclav Procházka
- Department of Radiology, University Hospital in Ostrava, 70852 Ostrava, Czech Republic
| | - Vaclav Brázda
- Institute of Biophysics, Academy of Sciences of The Czech Republic, 61265 Brno, Czech Republic
| | - Petr Pečinka
- Department of Biology and Ecology, Faculty of Science, University of Ostrava, 71000 Ostrava, Czech Republic.,Institute of Environmental Technologies, Faculty of Science, University of Ostrava, 71000 Ostrava, Czech Republic
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11
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Undifferentiated Adipose Tissue Stem Cell Transplantation Promotes Hepatic Regeneration, Ameliorates Histopathologic Damage of the Liver, and Upregulates the Expression of Liver Regeneration- and Liver-Specific Genes in a Rat Model of Partial Hepatectomy. Stem Cells Int 2018; 2018:1393607. [PMID: 29731771 PMCID: PMC5872619 DOI: 10.1155/2018/1393607] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2017] [Accepted: 12/06/2017] [Indexed: 02/01/2023] Open
Abstract
Objective Adipose tissue stem cells (ADSCs) present a promising therapeutic method to alleviate liver failure (LF). The purpose of this prospective study was to evaluate the efficacy of undifferentiated ADSC transplantation on liver regeneration and on the expression of liver regeneration- and liver-specific genes, following 60% partial hepatectomy (PHx). Methods Sixty female rats were subjected to PHx and were transplanted with 106 or 2 × 106 ADSCs, either into the portal vein (PV) or into the hepatic parenchyma. Animals of the control group were not transplanted and served as controls. Animals were sacrificed on the 4th, the 7th, or the 15th postoperative day (POD). Results The transplanted ADSCs were successfully engrafted into the liver parenchyma and ameliorated the histopathologic damage on the 7th and 15th POD. All transplanted animals demonstrated a significantly higher liver regeneration rate on the 4th and 7th POD, compared with the control group. The expression of hepatocyte growth factor, α-fetoprotein, tyrosine aminotransferase, hepatocyte nuclear factor 4a, and cytochrome P450 1A2 was significantly upregulated, compared with the control group. Conclusions Although undifferentiated, ADSC transplantation significantly enhanced the liver regeneration process. These findings may be proven clinically valuable, especially in cases of acute LF.
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Current Perspectives Regarding Stem Cell-Based Therapy for Liver Cirrhosis. Can J Gastroenterol Hepatol 2018; 2018:4197857. [PMID: 29670867 PMCID: PMC5833156 DOI: 10.1155/2018/4197857] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2017] [Accepted: 01/16/2018] [Indexed: 12/12/2022] Open
Abstract
Liver cirrhosis is a major cause of mortality and a common end of various progressive liver diseases. Since the effective treatment is currently limited to liver transplantation, stem cell-based therapy as an alternative has attracted interest due to promising results from preclinical and clinical studies. However, there is still much to be understood regarding the precise mechanisms of action. A number of stem cells from different origins have been employed for hepatic regeneration with different degrees of success. The present review presents a synopsis of stem cell research for the treatment of patients with liver cirrhosis according to the stem cell type. Clinical trials to date are summarized briefly. Finally, issues to be resolved and future perspectives are discussed with regard to clinical applications.
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Lu S, Shi G, Xu X, Wang G, Lan X, Sun P, Li X, Zhang B, Gu X, Ichim TE, Wang H. Human endometrial regenerative cells alleviate carbon tetrachloride-induced acute liver injury in mice. J Transl Med 2016; 14:300. [PMID: 27770815 PMCID: PMC5075169 DOI: 10.1186/s12967-016-1051-1] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2016] [Accepted: 10/05/2016] [Indexed: 01/08/2023] Open
Abstract
Background The endometrial regenerative cell (ERC) is a novel type of adult mesenchymal stem cell isolated from menstrual blood. Previous studies demonstrated that ERCs possess unique immunoregulatory properties in vitro and in vivo, as well as the ability to differentiate into functional hepatocyte-like cells. For these reasons, the present study was undertaken to explore the effects of ERCs on carbon tetrachloride (CCl4)–induced acute liver injury (ALI). Methods An ALI model in C57BL/6 mice was induced by administration of intraperitoneal injection of CCl4. Transplanted ERCs were intravenously injected (1 million/mouse) into mice 30 min after ALI induction. Liver function, pathological and immunohistological changes, cell tracking, immune cell populations and cytokine profiles were assessed 24 h after the CCl4 induction. Results ERC treatment effectively decreased the CCl4-induced elevation of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and improved hepatic histopathological abnormalities compared to the untreated ALI group. Immunohistochemical staining showed that over-expression of lymphocyte antigen 6 complex, locus G (Ly6G) was markedly inhibited, whereas expression of proliferating cell nuclear antigen (PCNA) was increased after ERC treatment. Furthermore, the frequency of CD4+ and CD8+ T cell populations in the spleen was significantly down-regulated, while the percentage of splenic CD4+CD25+FOXP3+ regulatory T cells (Tregs) was obviously up-regulated after ERC treatment. Moreover, splenic dendritic cells in ERC-treated mice exhibited dramatically decreased MHC-II expression. Cell tracking studies showed that transplanted PKH26-labeled ERCs engrafted to lung, spleen and injured liver. Compared to untreated controls, mice treated with ERCs had lower levels of IL-1β, IL-6, and TNF-α but higher level of IL-10 in both serum and liver. Conclusions Human ERCs protect the liver from acute injury in mice through hepatocyte proliferation promotion, as well as through anti-inflammatory and immunoregulatory effects.
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Affiliation(s)
- Shanzheng Lu
- Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China.,Tianjin General Surgery Institute, Tianjin, China
| | - Ganggang Shi
- Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China.,Tianjin General Surgery Institute, Tianjin, China
| | - Xiaoxi Xu
- Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China.,Tianjin General Surgery Institute, Tianjin, China
| | - Grace Wang
- Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - Xu Lan
- Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China.,Tianjin General Surgery Institute, Tianjin, China
| | - Peng Sun
- Department of General Surgery, Affiliated Hospital of Weifang Medical University, Shandong, China
| | - Xiang Li
- Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China.,Tianjin General Surgery Institute, Tianjin, China
| | - Baoren Zhang
- Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China.,Tianjin General Surgery Institute, Tianjin, China
| | - Xiangying Gu
- Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, China
| | | | - Hao Wang
- Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China. .,Tianjin General Surgery Institute, Tianjin, China.
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Liao N, Wu M, Pan F, Lin J, Li Z, Zhang D, Wang Y, Zheng Y, Peng J, Liu X, Liu J. Poly (dopamine) coated superparamagnetic iron oxide nanocluster for noninvasive labeling, tracking, and targeted delivery of adipose tissue-derived stem cells. Sci Rep 2016; 6:18746. [PMID: 26728448 PMCID: PMC4700528 DOI: 10.1038/srep18746] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2015] [Accepted: 11/25/2015] [Indexed: 02/06/2023] Open
Abstract
Tracking and monitoring of cells in vivo after transplantation can provide crucial information for stem cell therapy. Magnetic resonance imaging (MRI) combined with contrast agents is believed to be an effective and non-invasive technique for cell tracking in living bodies. However, commercial superparamagnetic iron oxide nanoparticles (SPIONs) applied to label cells suffer from shortages such as potential toxicity, low labeling efficiency, and low contrast enhancing. Herein, the adipose tissue-derived stem cells (ADSCs) were efficiently labeled with SPIONs coated with poly (dopamine) (SPIONs cluster@PDA), without affecting their viability, proliferation, apoptosis, surface marker expression, as well as their self-renew ability and multi-differentiation potential. The labeled cells transplanted into the mice through tail intravenous injection exhibited a negative enhancement of the MRI signal in the damaged liver-induced by carbon tetrachloride, and subsequently these homed ADSCs with SPIONs cluster@PDA labeling exhibited excellent repair effects to the damaged liver. Moreover, the enhanced target-homing to tissue of interest and repair effects of SPIONs cluster@PDA-labeled ADSCs could be achieved by use of external magnetic field in the excisional skin wound mice model. Therefore, we provide a facile, safe, noninvasive and sensitive method for external magnetic field targeted delivery and MRI based tracking of transplanted cells in vivo.
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Affiliation(s)
- Naishun Liao
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, P.R. China
- The Liver Center of Fujian Province, Fujian Medical University, Fuzhou 350025, P.R. China
| | - Ming Wu
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, P.R. China
- The Liver Center of Fujian Province, Fujian Medical University, Fuzhou 350025, P.R. China
| | - Fan Pan
- Department of Hepatobiliary Surgery, Fuzong Clinical College, Fujian Medical University, Fuzhou 350001, P.R. China
| | - Jiumao Lin
- Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, P.R. China
| | - Zuanfang Li
- Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, P.R. China
| | - Da Zhang
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, P.R. China
- The Liver Center of Fujian Province, Fujian Medical University, Fuzhou 350025, P.R. China
| | - Yingchao Wang
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, P.R. China
- The Liver Center of Fujian Province, Fujian Medical University, Fuzhou 350025, P.R. China
| | - Youshi Zheng
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, P.R. China
- The Liver Center of Fujian Province, Fujian Medical University, Fuzhou 350025, P.R. China
| | - Jun Peng
- Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, P.R. China
| | - Xiaolong Liu
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, P.R. China
- The Liver Center of Fujian Province, Fujian Medical University, Fuzhou 350025, P.R. China
| | - Jingfeng Liu
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, P.R. China
- The Liver Center of Fujian Province, Fujian Medical University, Fuzhou 350025, P.R. China
- Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350007, P.R. China
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Katselis C, Apostolou K, Feretis T, Papanikolaou IG, Zografos GC, Toutouzas K, Papalois A. Role of Stem Cells Transplantation in Tissue Regeneration After Acute or Chronic Acetaminophen Induced Liver Injury. J INVEST SURG 2015; 29:112-20. [PMID: 26650889 DOI: 10.3109/08941939.2015.1086040] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
PURPOSE Acetaminophen-induced liver injury (APAP) is recognized as a frequent etiologic factor responsible for hepatic damage in the developed world. Management remains still elusive as treatment options are limited and their results are inconclusive. Consequently new strategies are explored at the experimental level. Mesenchymal stem cells (MSCs) present a promising modality as they can promote liver regeneration (LG) and compensate acute liver injury (ALI). MATERIALS AND METHODS Our research was focused on articles related to drug-induced liver injury, mechanisms of liver regeneration (LG) after Acute Liver Injury (ALI) and recent experimental protocols of Mesenchymal Stem Cells (MSCs) transplantation after chemical insult. All these studies are cited on Pubmed and MedLine. RESULTS This review has three distinct sections. First recent developments in ALI pathogenesis are presented. The second section covers cellular pathways and histological findings relevant to liver regeneration. The final chapter analyzes MSCs transplantation protocols after ALI and interrelation between liver regeneration and hepatic differentiation of MSCs. CONCLUSION Adipose tissue stem cells (ADSCs) and (MSCs) transplantation represents a promising modality in severe ALI management although many aspects remain to be clarified.
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Affiliation(s)
- Charalampos Katselis
- a Department of Propaedeutic Surgery , University of Athens, School of Medicine, General Hospital of Athens "Hippocration" , Athens , Greece.,b Experimental - Research Center , ELPEN Pharmaceuticals , Pikermi , Attica
| | - Konstantinos Apostolou
- a Department of Propaedeutic Surgery , University of Athens, School of Medicine, General Hospital of Athens "Hippocration" , Athens , Greece.,b Experimental - Research Center , ELPEN Pharmaceuticals , Pikermi , Attica
| | - Themistoklis Feretis
- a Department of Propaedeutic Surgery , University of Athens, School of Medicine, General Hospital of Athens "Hippocration" , Athens , Greece.,b Experimental - Research Center , ELPEN Pharmaceuticals , Pikermi , Attica
| | - Ioannis G Papanikolaou
- a Department of Propaedeutic Surgery , University of Athens, School of Medicine, General Hospital of Athens "Hippocration" , Athens , Greece.,b Experimental - Research Center , ELPEN Pharmaceuticals , Pikermi , Attica
| | - George C Zografos
- a Department of Propaedeutic Surgery , University of Athens, School of Medicine, General Hospital of Athens "Hippocration" , Athens , Greece
| | - Konstantinos Toutouzas
- a Department of Propaedeutic Surgery , University of Athens, School of Medicine, General Hospital of Athens "Hippocration" , Athens , Greece
| | - Apostolos Papalois
- a Department of Propaedeutic Surgery , University of Athens, School of Medicine, General Hospital of Athens "Hippocration" , Athens , Greece.,b Experimental - Research Center , ELPEN Pharmaceuticals , Pikermi , Attica
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Tsolaki E, Yannaki E. Stem cell-based regenerative opportunities for the liver: State of the art and beyond. World J Gastroenterol 2015; 21:12334-12350. [PMID: 26604641 PMCID: PMC4649117 DOI: 10.3748/wjg.v21.i43.12334] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2015] [Revised: 09/16/2015] [Accepted: 10/20/2015] [Indexed: 02/06/2023] Open
Abstract
The existing mismatch between the great demand for liver transplants and the number of available donor organs highlights the urgent need for alternative therapeutic strategies in patients with acute or chronic liver failure. The rapidly growing knowledge on stem cell biology and the intrinsic repair processes of the liver has opened new avenues for using stem cells as a cell therapy platform in regenerative medicine for hepatic diseases. An impressive number of cell types have been investigated as sources of liver regeneration: adult and fetal liver hepatocytes, intrahepatic stem cell populations, annex stem cells, adult bone marrow-derived hematopoietic stem cells, endothelial progenitor cells, mesenchymal stromal cells, embryonic stem cells, and induced pluripotent stem cells. All these highly different cell types, used either as cell suspensions or, in combination with biomaterials as implantable liver tissue constructs, have generated great promise for liver regeneration. However, fundamental questions still need to be addressed and critical hurdles to be overcome before liver cell therapy emerges. In this review, we summarize the state-of-the-art in the field of stem cell-based therapies for the liver along with existing challenges and future perspectives towards a successful liver cell therapy that will ultimately deliver its demanding goals.
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