Establishing an hTERT-driven immortalized umbilical cord-derived mesenchymal stem cell line and its therapeutic application in mice with liver failure

Author:

Chen Qi12,Jin Meixian1,Wang Simin1,Wang Kexin3,Chen Liqin1,Zhu Xiaojuan4,Zhang Ying3,Wang Yi3,Li Yang3,Li Shao3,Zeng Youmin1,Feng Lei3ORCID,Yang Wanren3,Gao Yi3ORCID,Zhou Shuqin1ORCID,Peng Qing3ORCID

Affiliation:

1. Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China

2. Department of Anesthesiology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China

3. General Surgery Center, Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China

4. Department of Anesthesiology, The First People’ s Hospital of Kashi, Kashgar, Xinjiang, China

Abstract

Acute liver failure (ALF) is characterized by rapid liver cell destruction. It is a multi-etiological and fulminant complication with a clinical mortality of over 80%. Therapy using mesenchymal stem cells (MSCs) or MSCs-derived exosomes can alleviate acute liver injury, which has been demonstrated in animal experiments and clinical application. However, similar to other stem cells, different cell sources, poor stability, cell senescence and other factors limit the clinical application of MSCs. To achieve mass production and quality control on stem cells and their exosomes, transfecting umbilical cord mesenchymal stem cell (UCMSC) with lentivirus overexpressing human telomerase reverse transcriptase (hTERT) gene, the hTERT-UCMSC was constructed as an immortalized MSC cell line. Compared with the primary UCMSC (P3) and immortalized cell line hTERT-UCMSC at early passage (P10), the hTERT-UCMSC retained the key morphological and physiological characteristics of UCMSC at the 35th passage (P35), and showed no signs of carcinogenicity and toxic effect in mice. There was no difference in either exosome production or characteristics of exosomes among cultures from P3 primary cells, P10 and P35 immortalized hTERT-UCMSCs. Inoculation of either hTERT-UCMSC (P35) or its exosomes improved the survival rate and liver function of ALF mice induced by thioacetamide (TAA). Our findings suggest that this immortalized cell line can maintain its characteristics in long-term culture. Inoculation of hTERT-UCMSC and its exosomes could potentially be used in clinics for the treatment of liver failure in the future.

Funder

National Natural Science Foundation of China

basic and applied basic research foundation of guangdong province

the National Key R&D Program of China

the Natural Science Foundation of Xinjiang Uygur Autonomous Region

Publisher

SAGE Publications

Subject

Biomedical Engineering,Biomaterials,Medicine (miscellaneous)

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