Genetic Modification by Overexpression of Target Gene in Mesenchymal Stromal Cell for Treating Liver Diseases

Overview

Journal J Mol Med (Berl)

Specialty General Medicine

Date 2021 Jan 3

PMID 33388882

Citations 6

Authors

Chenxia Hu

Lingfei Zhao

Lanjuan Li

Affiliations

Soon will be listed here.

Abstract

Different hepatoxic factors cause irreversible liver injury, leading to liver failure, cirrhosis, and cancer in mammals. Liver transplantation is the only effective strategy, which can improve the prognosis of patients with end-stage liver diseases, but it is limited by liver donor shortage, expensive costs, liver graft rejection and dysfunction, and recurring liver failure. Recently, mesenchymal stromal cells (MSCs) isolated from various tissues are regarded as the main stem cell type with therapeutic effects in liver diseases because of their hepatogenic differentiation, anti-inflammatory, immuoregulatory, anti-apoptotic, antifibrotic, and antitumor capacities. To further improve the therapeutic effects of MSCs, multiple studies showed that genetically engineered MSCs have increased regenerative capacities and are able to more effectively inhibit cell death. Moreover, they are able to secrete therapeutic proteins for attenuating liver injury in liver diseases. In this review, we mainly focus on gene overexpression for reprogramming MSCs to increase their therapeutic effects in treating various liver diseases. We described the potential mechanisms of MSCs with gene overexpression in attenuating liver injury, and we recommend further expansion of experiments to discover more gene targets and optimized gene delivery methods for MSC-based regenerative medicine. We also discussed the potential hurdles in genetic engineering MSCs. In conclusion, we highlight that we need to overcome all scientific hurdles before genetically modified MSC therapy can be translated into clinical practices for patients with liver diseases.

Citing Articles

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Advance of Mesenchymal Stem Cells in Chronic End-Stage Liver Disease Control.

Gao Y, Yin X, Ren X Stem Cells Int. 2022; 2022:1526217.

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Recent advances in the therapeutic efficacy of hepatocyte growth factor gene-modified mesenchymal stem cells in multiple disease settings.

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References

Hu C, Li L . The immunoregulation of mesenchymal stem cells plays a critical role in improving the prognosis of liver transplantation. J Transl Med. 2019; 17(1):412. PMC: 6905033. DOI: 10.1186/s12967-019-02167-0. View

Ascha M, Ascha M, Hanouneh I . Management of immunosuppressant agents following liver transplantation: Less is more. World J Hepatol. 2016; 8(3):148-61. PMC: 4724578. DOI: 10.4254/wjh.v8.i3.148. View

Dhawan A, Puppi J, Hughes R, Mitry R . Human hepatocyte transplantation: current experience and future challenges. Nat Rev Gastroenterol Hepatol. 2010; 7(5):288-98. DOI: 10.1038/nrgastro.2010.44. View

Shroff G, Dhanda Titus J, Shroff R . A review of the emerging potential therapy for neurological disorders: human embryonic stem cell therapy. Am J Stem Cells. 2017; 6(1):1-12. PMC: 5435646. View

Shi Y, Inoue H, Wu J, Yamanaka S . Induced pluripotent stem cell technology: a decade of progress. Nat Rev Drug Discov. 2016; 16(2):115-130. PMC: 6416143. DOI: 10.1038/nrd.2016.245. View

Sauer V, Roy-Chowdhury N, Guha C, Roy-Chowdhury J . Induced pluripotent stem cells as a source of hepatocytes. Curr Pathobiol Rep. 2015; 2(1):11-20. PMC: 4312414. DOI: 10.1007/s40139-013-0039-2. View

Forbes S, Gupta S, Dhawan A . Cell therapy for liver disease: From liver transplantation to cell factory. J Hepatol. 2015; 62(1 Suppl):S157-69. DOI: 10.1016/j.jhep.2015.02.040. View

Asgari S, Moslem M, Bagheri-Lankarani K, Pournasr B, Miryounesi M, Baharvand H . Differentiation and transplantation of human induced pluripotent stem cell-derived hepatocyte-like cells. Stem Cell Rev Rep. 2011; 9(4):493-504. DOI: 10.1007/s12015-011-9330-y. View

Tolosa L, Caron J, Hannoun Z, Antoni M, Lopez S, Burks D . Transplantation of hESC-derived hepatocytes protects mice from liver injury. Stem Cell Res Ther. 2015; 6:246. PMC: 4676869. DOI: 10.1186/s13287-015-0227-6. View

10.

Carpentier A, Tesfaye A, Chu V, Nimgaonkar I, Zhang F, Lee S . Engrafted human stem cell-derived hepatocytes establish an infectious HCV murine model. J Clin Invest. 2014; 124(11):4953-64. PMC: 4347235. DOI: 10.1172/JCI75456. View

11.

Kajiwara M, Aoi T, Okita K, Takahashi R, Inoue H, Takayama N . Donor-dependent variations in hepatic differentiation from human-induced pluripotent stem cells. Proc Natl Acad Sci U S A. 2012; 109(31):12538-43. PMC: 3411998. DOI: 10.1073/pnas.1209979109. View

12.

Yoshida G . Emerging roles of Myc in stem cell biology and novel tumor therapies. J Exp Clin Cancer Res. 2018; 37(1):173. PMC: 6062976. DOI: 10.1186/s13046-018-0835-y. View

13.

Chae Y, Won Jun D, Lee J, Saeed W, Kang H, Jang K . The Use of Foxa2-Overexpressing Adipose Tissue-Derived Stem Cells in a Scaffold System Attenuates Acute Liver Injury. Gut Liver. 2019; 13(4):450-460. PMC: 6622567. DOI: 10.5009/gnl18235. View

14.

Di Rocco G, Gentile A, Antonini A, Truffa S, Piaggio G, Capogrossi M . Analysis of biodistribution and engraftment into the liver of genetically modified mesenchymal stromal cells derived from adipose tissue. Cell Transplant. 2012; 21(9):1997-2008. DOI: 10.3727/096368911X637452. View

15.

Tang Y, Li Q, Meng F, Huang X, Li C, Zhou X . Therapeutic Potential of HGF-Expressing Human Umbilical Cord Mesenchymal Stem Cells in Mice with Acute Liver Failure. Int J Hepatol. 2016; 2016:5452487. PMC: 4789068. DOI: 10.1155/2016/5452487. View

16.

Wang K, Li Y, Zhu T, Zhang Y, Li W, Lin W . Overexpression of c-Met in bone marrow mesenchymal stem cells improves their effectiveness in homing and repair of acute liver failure. Stem Cell Res Ther. 2017; 8(1):162. PMC: 5499016. DOI: 10.1186/s13287-017-0614-2. View

17.

Yu Y, Yao A, Chen N, Pu L, Fan Y, Lv L . Mesenchymal stem cells over-expressing hepatocyte growth factor improve small-for-size liver grafts regeneration. Mol Ther. 2007; 15(7):1382-9. DOI: 10.1038/sj.mt.6300202. View

18.

Du Z, Wei C, Yan J, Han B, Zhang M, Peng C . Mesenchymal stem cells overexpressing C-X-C chemokine receptor type 4 improve early liver regeneration of small-for-size liver grafts. Liver Transpl. 2012; 19(2):215-25. DOI: 10.1002/lt.23577. View

19.

Zheng Y, Zhang X, Huang Z, Lin C, Lai J, Gu Y . Amniotic-fluid-derived mesenchymal stem cells overexpressing interleukin-1 receptor antagonist improve fulminant hepatic failure. PLoS One. 2012; 7(7):e41392. PMC: 3402415. DOI: 10.1371/journal.pone.0041392. View

20.

Ye Z, Lu W, Liang L, Tang M, Wang Y, Li Z . Mesenchymal stem cells overexpressing hepatocyte nuclear factor-4 alpha alleviate liver injury by modulating anti-inflammatory functions in mice. Stem Cell Res Ther. 2019; 10(1):149. PMC: 6537220. DOI: 10.1186/s13287-019-1260-7. View