Human Menstrual Blood-Derived Stem Cells Ameliorate Liver Fibrosis in Mice by Targeting Hepatic Stellate Cells via Paracrine Mediators.
Mesenchymal stem cells (MSCs) may have potential applications in regenerative medicine for the treatment of chronic liver diseases (CLDs). Human menstrual blood is a novel source of MSCs, termed menstrual blood-derived stem cells (MenSCs). Compared with bone marrow MSCs, MenSCs exhibit a higher proliferation rate and they can be obtained through a simple, safe, painless procedure without ethical concerns. Although the therapeutic efficacy of MenSCs has been explored in some diseases, their effects on liver fibrosis are still unclear. In the present study, we investigated the therapeutic effects of MenSC transplantation in a carbon tetrachloride-induced mouse model of liver fibrosis. These results revealed that MenSCs markedly improved liver function, attenuated collagen deposition, and inhibited activated hepatic stellate cells up to 2 weeks after transplantation. Moreover, tracking of green fluorescent protein-expressing MenSCs demonstrated that transplanted cells migrated to the sites of injury, but few differentiated into functional hepatocyte-like cells. Transwell coculturing experiments also showed that MenSCs suppressed proliferation of LX-2 cells (an immortalized hepatic stellate cell line) through secretion of monocyte chemoattractant protein-1, interleukin-6, hepatocyte growth factor, growth-related oncogene, interleukin-8, and osteoprotegerin. Collectively, our results provided preliminary evidence for the antifibrotic capacity of MenSCs in liver fibrosis and suggested that these cells may be an alternative therapeutic approach for the treatment of CLDs. Stem Cells Translational Medicine 2017;6:272-284.
Institute of Cell and Development, College of Life Sciences, Zhejiang University, Hangzhou, People's Republic of China.|State Key Laboratory for Diagnosis and Treatment of Infectious Diseases and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.|Molecular Diagnosis Division, Zhejiang-California International Nanosystem Institute, Zhejiang University, Hangzhou, People's Republic of China.
Lijun
L
Chen
Institute of Cell and Development, College of Life Sciences, Zhejiang University, Hangzhou, People's Republic of China.|State Key Laboratory for Diagnosis and Treatment of Infectious Diseases and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.|Molecular Diagnosis Division, Zhejiang-California International Nanosystem Institute, Zhejiang University, Hangzhou, People's Republic of China.
Chunfeng
C
Zhang
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
Lu
L
Chen
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
Xiaojun
X
Wang
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
Bingyu
B
Xiang
Institute of Cell and Development, College of Life Sciences, Zhejiang University, Hangzhou, People's Republic of China.
Xiaoxing
X
Wu
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
Yang
Y
Guo
Clinical Research Institute, Zhejiang Provincial People's Hospital, Hangzhou, People's Republic of China.
Xiaozhou
X
Mou
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
Li
L
Yuan
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
Bo
B
Chen
Institute of Cell and Development, College of Life Sciences, Zhejiang University, Hangzhou, People's Republic of China.
Jinfu
J
Wang
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.|Molecular Diagnosis Division, Zhejiang-California International Nanosystem Institute, Zhejiang University, Hangzhou, People's Republic of China.|Institute for Cell-Based Drug Development of Zhejiang Province, Hangzhou, People's Republic of China.
Charlie
C
Xiang
D000199:Actins / Q000378:metabolism; D000818:Animals; D002251:Carbon Tetrachloride; D059447:Cell Cycle Checkpoints; D002465:Cell Movement; D049109:Cell Proliferation; D048430:Cell Shape; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation; D055166:Hepatic Stellate Cells / Q000166:cytology*; D006801:Humans; D016130:Immunophenotyping; D008103:Liver Cirrhosis / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D008297:Male; D008598:Menstruation; D008813:Mice, Inbred ICR; D019899:Paracrine Communication; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
C541116:ACTA2 protein, human; D000199:Actins; D016207:Cytokines; D053773:Transforming Growth Factor beta1; D003094:Collagen; D002251:Carbon Tetrachloride
Cellular therapy; Liver fibrosis; Menstrual blood-derived stem cells; Paracrine protein factors; Stem cell transplantation