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...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-03-01
|
| Series: | Regenerative Therapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352320425000173 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832540414885756928 |
|---|---|
| author | Natsuki Ishikawa Yusuke Watanabe Yuichirou Maeda Tomoaki Yoshida Naruhiro Kimura Hiroyuki Abe Akira Sakamaki Hiroteru Kamimura Takeshi Yokoo Kenya Kamimura Atsunori Tsuchiya Shuji Terai |
| author_facet | Natsuki Ishikawa Yusuke Watanabe Yuichirou Maeda Tomoaki Yoshida Naruhiro Kimura Hiroyuki Abe Akira Sakamaki Hiroteru Kamimura Takeshi Yokoo Kenya Kamimura Atsunori Tsuchiya Shuji Terai |
| author_sort | Natsuki Ishikawa |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-ae0e901f6034447db3b04550b9ab3cd8 |
| institution | Kabale University |
| issn | 2352-3204 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Regenerative Therapy |
| spelling | doaj-art-ae0e901f6034447db3b04550b9ab3cd82025-02-05T04:32:10ZengElsevierRegenerative Therapy2352-32042025-03-0128509516Human placental extract improves liver cirrhosis in mice with regulation of macrophages and senescent cellsNatsuki Ishikawa0Yusuke Watanabe1Yuichirou Maeda2Tomoaki Yoshida3Naruhiro Kimura4Hiroyuki Abe5Akira Sakamaki6Hiroteru Kamimura7Takeshi Yokoo8Kenya Kamimura9Atsunori Tsuchiya10Shuji Terai11Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, JapanDivision of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan; Division of Preemptive Medicine for Digestive Disease and Healthy Active Life, School of Medicine, Niigata University, Niigata, Japan; Corresponding author. Division of Preemptive Medicine for Digestive Disease and Healthy Active Life, School of Medicine, Niigata University, 1-757 Asahimachi-dori, Chuo-ku, Niigata, 951-8510, Japan.Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, JapanDivision of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan; Division of Preemptive Medicine for Digestive Disease and Healthy Active Life, School of Medicine, Niigata University, Niigata, JapanDivision of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, JapanDivision of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, JapanDivision of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, JapanDivision of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, JapanDivision of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan; Division of Preemptive Medicine for Digestive Disease and Healthy Active Life, School of Medicine, Niigata University, Niigata, JapanDivision of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, JapanDivision of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, JapanDivision of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan; Corresponding author. Division of Gastroenterology & Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata 951-8510, Japan.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.http://www.sciencedirect.com/science/article/pii/S2352320425000173Human placental extractSpatial transcriptomicsLiver cirrhosis |
| spellingShingle | Natsuki Ishikawa Yusuke Watanabe Yuichirou Maeda Tomoaki Yoshida Naruhiro Kimura Hiroyuki Abe Akira Sakamaki Hiroteru Kamimura Takeshi Yokoo Kenya Kamimura Atsunori Tsuchiya Shuji Terai Human placental extract improves liver cirrhosis in mice with regulation of macrophages and senescent cells Regenerative Therapy Human placental extract Spatial transcriptomics Liver cirrhosis |
| title | Human placental extract improves liver cirrhosis in mice with regulation of macrophages and senescent cells |
| title_full | Human placental extract improves liver cirrhosis in mice with regulation of macrophages and senescent cells |
| title_fullStr | Human placental extract improves liver cirrhosis in mice with regulation of macrophages and senescent cells |
| title_full_unstemmed | Human placental extract improves liver cirrhosis in mice with regulation of macrophages and senescent cells |
| title_short | Human placental extract improves liver cirrhosis in mice with regulation of macrophages and senescent cells |
| title_sort | human placental extract improves liver cirrhosis in mice with regulation of macrophages and senescent cells |
| topic | Human placental extract Spatial transcriptomics Liver cirrhosis |
| url | http://www.sciencedirect.com/science/article/pii/S2352320425000173 |
| work_keys_str_mv | AT natsukiishikawa humanplacentalextractimproveslivercirrhosisinmicewithregulationofmacrophagesandsenescentcells AT yusukewatanabe humanplacentalextractimproveslivercirrhosisinmicewithregulationofmacrophagesandsenescentcells AT yuichiroumaeda humanplacentalextractimproveslivercirrhosisinmicewithregulationofmacrophagesandsenescentcells AT tomoakiyoshida humanplacentalextractimproveslivercirrhosisinmicewithregulationofmacrophagesandsenescentcells AT naruhirokimura humanplacentalextractimproveslivercirrhosisinmicewithregulationofmacrophagesandsenescentcells AT hiroyukiabe humanplacentalextractimproveslivercirrhosisinmicewithregulationofmacrophagesandsenescentcells AT akirasakamaki humanplacentalextractimproveslivercirrhosisinmicewithregulationofmacrophagesandsenescentcells AT hiroterukamimura humanplacentalextractimproveslivercirrhosisinmicewithregulationofmacrophagesandsenescentcells AT takeshiyokoo humanplacentalextractimproveslivercirrhosisinmicewithregulationofmacrophagesandsenescentcells AT kenyakamimura humanplacentalextractimproveslivercirrhosisinmicewithregulationofmacrophagesandsenescentcells AT atsunoritsuchiya humanplacentalextractimproveslivercirrhosisinmicewithregulationofmacrophagesandsenescentcells AT shujiterai humanplacentalextractimproveslivercirrhosisinmicewithregulationofmacrophagesandsenescentcells |