Human placental extract improves liver cirrhosis in mice with regulation of macrophages and senescent cells

Human placental extract improves liver cirrhosis in mice with regulation of macrophages and senescent cells

Introduction: Cirrhosis is a disease with poor prognosis that requires the development of a novel therapeutic approach alternative to liver transplantation. In this study, we focused on the placenta and aimed to clarify the effects of human placental extract (HPE) on cirrhosis. Methods: A mouse mode...

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Main Authors: Natsuki Ishikawa, Yusuke Watanabe, Yuichirou Maeda, Tomoaki Yoshida, Naruhiro Kimura, Hiroyuki Abe, Akira Sakamaki, Hiroteru Kamimura, Takeshi Yokoo, Kenya Kamimura, Atsunori Tsuchiya, Shuji Terai
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Regenerative Therapy
Subjects:
Human placental extract
Spatial transcriptomics
Liver cirrhosis
Online Access:http://www.sciencedirect.com/science/article/pii/S2352320425000173
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Summary:Introduction: Cirrhosis is a disease with poor prognosis that requires the development of a novel therapeutic approach alternative to liver transplantation. In this study, we focused on the placenta and aimed to clarify the effects of human placental extract (HPE) on cirrhosis. Methods: A mouse model of carbon tetrachloride-induced cirrhosis was used to evaluate the effect of HPE administration subcutaneously and compared with the control group (n = 8 for each group). In vitro and in vivo, real time-PCR and immunostaining were performed for HPE mechanistic analysis. Spatial transcriptomics was also performed for detailed analysis of the effect of HPE on cirrhosis. Results: HPE administration improved serum ALT levels compared to control mice. Furthermore, there was a decrease in the number of senescent cells in the liver and the mRNA levels of secrete senescence-associated secretory phenotype factors and Cdkn2a (p16). In vitro, HPE induced macrophage polarization to the anti-inflammatory M2 phenotype. Spatial transcriptomics was also performed to analyze the underlying anti-inflammatory mechanism. The results showed that HPE strongly polarized macrophages to the M2 phenotype, especially in macrophage-rich regions in the liver. Gene expression pathway analysis using spatial transcriptomics also revealed the possibility of improving senescent cell-derived inflammation via mitochondrial function. Conclusions: HPE improves serum ALT levels via anti-inflammatory mechanisms in macrophages and senescent cells. HPE serves as a novel agent for cirrhosis treatment.
ISSN:2352-3204

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