Improvement in aged liver regeneration using cell transplantation with chemically induced liver progenitors

IF 3.2 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Journal of Hepato‐Biliary‐Pancreatic Sciences Pub Date : 2024-04-03 DOI:10.1002/jhbp.1425

Kunihito Matsuguma, Takanobu Hara, Daisuke Miyamoto, Akihiko Soyama, Hajime Matsushima, Masayuki Fukumoto, Hajime Imamura, Mampei Yamashita, Tomohiko Adachi, Susumu Eguchi

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Abstract

Background

A decrease in the regenerative capacity of age-damaged liver tissue has been reported. Liver progenitor cells may play an important role in the regeneration of injured livers. In the present study we aimed to investigate improvements in the regenerative capacity of age-damaged livers using chemically induced liver progenitors (CLiPs) derived from mature hepatocytes.

Methods

Old (>90 weeks) and young (<20 weeks) mice underwent 70% hepatectomy, with or without trans-splenic CLiP administration. The residual liver/bodyweight (LW/BW) ratio was measured on postoperative days 1 and 7, and changes in liver regeneration and histology were evaluated.

Results

At 7 days post-hepatectomy, LW/BW ratios were significantly better in CLiP-treated old mice than in untreated old mice (p = .02). By contrast, no effect of CLiP transplantation was observed in young mice (p = .62). Immunofluorescence staining of liver tissue after CLiP administration showed an increase in Ki67-positive cells (p < .01). Flow cytometry analysis of green fluorescent protein-labeled CLiPs indicated that transplanted CLiPs differentiated into mature hepatocytes and were present in the recipient liver.

Conclusions

CLiP transplantation appears to ameliorate the age-related decline in liver regeneration in mice.

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利用化学诱导肝脏祖细胞移植改善老年肝脏再生

背景据报道，受年龄损伤的肝组织再生能力下降。肝祖细胞可能在损伤肝脏的再生过程中发挥重要作用。本研究旨在利用从成熟肝细胞中提取的化学诱导肝祖细胞（CLiPs），研究如何提高老化损伤肝脏的再生能力。方法对老龄（90 周）和幼龄（20 周）小鼠进行 70% 的肝切除术，同时给予或不给予经脾脏 CLiP。术后第 1 天和第 7 天测量了残肝/体重（LW/BW）比率，并评估了肝脏再生和组织学方面的变化。相比之下，CLiP 移植对年轻小鼠没有影响（p = .62）。服用 CLiP 后，肝组织的免疫荧光染色显示 Ki67 阳性细胞有所增加（p = 0.01）。对绿色荧光蛋白标记的CLiPs进行流式细胞术分析表明，移植的CLiPs分化为成熟的肝细胞，并存在于受体肝脏中。

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来源期刊

Journal of Hepato‐Biliary‐Pancreatic Sciences GASTROENTEROLOGY & HEPATOLOGY-SURGERY

自引率

10.00%

发文量

178

审稿时长

6-12 weeks

期刊介绍： The Journal of Hepato-Biliary-Pancreatic Sciences (JHBPS) is the leading peer-reviewed journal in the field of hepato-biliary-pancreatic sciences. JHBPS publishes articles dealing with clinical research as well as translational research on all aspects of this field. Coverage includes Original Article, Review Article, Images of Interest, Rapid Communication and an announcement section. Letters to the Editor and comments on the journal’s policies or content are also included. JHBPS welcomes submissions from surgeons, physicians, endoscopists, radiologists, oncologists, and pathologists.