All experiments in this protocol were approved by the Veterinary Authorities of the Jiangxi Provincial People&#39;s Hospital (number 70/2022). Furthermore, all experimental steps were performed in strict compliance with the Institutional Animal Care and Use Committee.
1. Start of surgery
NOTE: Male C57BL/6 mice weighing 20-22 g were housed in a well-ventilated cage, maintained in a standard pathogen-free environment with a 12 h/12 h light/dark cycle. ...

Studying Liver Regeneration of ALLPS in Animal Models for Staged Hepatectomy

<ol>
	<li>Michalopoulos, G. K., Bhushan, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Liver+regeneration:+Biological+and+pathological+mechanisms+and+implications.">Liver regeneration: Biological and pathological mechanisms and implications.</a> Nat Rev Gastroenterol Hepatol. 18 (1), 40-55 (2021).</li><li>Chapelle, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Estimation+of+the+future+remnant+liver+function+is+a+better+tool+to+pr+edict+post-hepatectomy+liver+failure+than+platelet-based+liver+scores.">Estimation of the future remnant liver function is a better tool to pr edict post-hepatectomy liver failure than platelet-based liver scores.</a> Eur J Surg Oncol. 43 (12), 2277-2284 (2017).</li><li>Isfordink, C. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Portal+vein+ligation+versus+portal+vein+embolization+for+induction+of+hypertrophy+of+the+future+liver+remnant:+A+systematic+review+and+meta-analysis.">Portal vein ligation versus portal vein embolization for induction of hypertrophy of the future liver remnant: A systematic review and meta-analysis.</a> Surg Oncol. 26 (3), 257-267 (2017).</li><li>Linecker, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Risk+adjustment+in+alpps+is+associated+with+a+dramatic+decrease+in+ear+ly+mortality+and+morbidity.">Risk adjustment in alpps is associated with a dramatic decrease in ear ly mortality and morbidity.</a> Ann Surg. 266 (5), 779-786 (2017).</li><li>Darnis, B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Subtotal+hepatectomy+in+swine+for+studying+small-for-size+syndrome+and+portal+inflow+modulation:+Is+it+reliable.">Subtotal hepatectomy in swine for studying small-for-size syndrome and portal inflow modulation: Is it reliable.</a> HPB (Oxford). 17 (10), 881-888 (2015).</li><li>Casellas, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Inbred+mouse+strains+and+genetic+stability:+A+review.">Inbred mouse strains and genetic stability: A review.</a> Animal. 5 (1), 1-7 (2011).</li><li>Zhang, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Evolution+of+associating+liver+partition+and+portal+vein+ligation+for+staged+hepatectomy+from+2012+to+2021:+A+bibliometric+analysis.+Review.">Evolution of associating liver partition and portal vein ligation for staged hepatectomy from 2012 to 2021: A bibliometric analysis. Review.</a> Int J Surg. 103, 106648 (2022).</li><li>Parola, M., Pinzani, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Liver+fibrosis:+Pathophysiology,+pathogenetic+targets+and+clinical+iss+ues.">Liver fibrosis: Pathophysiology, pathogenetic targets and clinical iss ues.</a> Mol Aspects Med. 65, 37-55 (2019).</li><li>Kikuchi, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Impact+of+associating+liver+partition+and+portal+vein+occlusion+for+st+aged+hepatectomy+on+tumor+growth+in+a+mouse+model+of+liver+metastasis.">Impact of associating liver partition and portal vein occlusion for st aged hepatectomy on tumor growth in a mouse model of liver metastasis.</a> Eur J Surg Oncol. 44 (1), 130-138 (2018).</li><li>Schlegel, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Alpps:+From+human+to+mice+highlighting+accelerated+and+novel+mechanism+s+of+liver+regeneration.">Alpps: From human to mice highlighting accelerated and novel mechanism s of liver regeneration.</a> Ann Surg. 260 (5), 839-846 (2014).</li><li>Dili, A., Lebrun, V., Bertrand, C., Leclercq, I. 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The authors have no conflicts of interest to declare.

This study presents a protocol for the initial phase of ALPPS surgery in mice, involving partial ligation of the portal vein and division of the median liver lobe. This method closely mimics the human ALPPS procedure, with the mouse liver&#39;s unique lobular structure and dual portal venous supply to the median lobe ensuring distinct blood flow post-surgery11. It is noteworthy that the ALPPS procedure comprises two distinct surgical stages. In this study, we exclusively present the initial stage ...

The liver harbors formidable regenerative potential, swiftly proliferating and restoring metabolic demands within a mere 3 months following resection for diverse hepatic ailments1. However, the imperative to ascertain the completeness of tumor margins necessitates the inevitability of expansive hepatic excision. Thus, ensuring an ample volume of the participatory hepatic milieu, known as the future liver remnant (FLR), assumes paramount importance2. ALPPS has been a breakthrough technique in hepatic surgery over the past few decades, particularly tailored for patients with inadequate residual hepatic volume subsequent to tumor resection, heralded as one of the most auspicious breakthroughs in the realm of hepatic oncological surgery3.
Remarkable progress has been made in developing ALPPS animal models. An ideal model typically requires independent blood inflow (portal vein and hepatic artery) and outflow (hepatic vein) in the preserved hepatic lobe and a clear separation between the preserved and the to-be-resected hepatic lobes to prevent collateral circulation4. Although ALPPS stimulates rapid hepatic regeneration in the remaining liver tissue, the specific mechanisms of this process are still unclear.
Currently, ALPPS models are categorized into three types: large animal models (e.g., swine and sheep), medium-sized models (e.g., rabbits and rodents), and small models (e.g., mice)5. The use of mice, with their quick breeding and ease of genetic modification, is particularly effective for in-depth studies of hepatic regeneration mechanisms6. Moreover, the liver structure of mice, especially their middle hepatic vein, closely resembles that of humans, making them highly suitable for ALPPS model development.
It is important to note that most hepatocellular carcinoma patients in clinical practice have underlying liver conditions, unlike the healthy liver models typically used in studies7. Thus, using mice preconditioned with hepatic fibrosis or viral infections can more accurately simulate the surgical responses and postoperative liver regeneration seen in patients with various liver diseases8. This approach could reveal new therapeutic targets of clinical relevance.
So far, a few renowned research groups, such as those at the University of Zurich and the University of Tokyo, have successfully developed murine ALPPS models9,10. Creating a standardized murine model under controlled conditions could advance our understanding of the rapid liver regeneration observed after ALPPS procedures.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>5% glucose injection (500 mL)</td>
			<td>Shapuaisi pharma (http://www.zjspas.com/)</td>
			<td>H20003666</td>
			<td>Efficient, cheap,Easy to access</td>
		</tr>
		<tr>
			<td>anaesthesia machine</td>
			<td>RWD (www.rwdls.com)</td>
			<td>R500</td>
			<td>low price and valuable quality. It is suitable for operations with beginners</td>
		</tr>
		<tr>
			<td>C57 BL/6</td>
			<td>The Jackson Lab</td>
			<td>22349-2023</td>
			<td>Stability of strains</td>
		</tr>
		<tr>
			<td>isoflurane</td>
			<td>KCSW (kcsw.szqisoubao.com)</td>
			<td>H19980141</td>
			<td>durable, cost-effective</td>
		</tr>
		<tr>
			<td>meloxicam</td>
			<td>Boehringer-Ingelheim</td>
			<td>H20020217</td>
			<td>Durable and efficient</td>
		</tr>
		<tr>
			<td>microforceps</td>
			<td>maydeal</td>
			<td>60018920</td>
			<td>Durable and efficient</td>
		</tr>
		<tr>
			<td>microinstrument</td>
			<td>CH microsurgical instrument factory</td>
			<td>HC-A804-1</td>
			<td>durable, cost-effective</td>
		</tr>
		<tr>
			<td>sodium lactate ringer</td>
			<td>Shapuaisi pharma (http://www.zjspas.com/)</td>
			<td>H20193277</td>
			<td>Efficient, cheap, easy to access</td>
		</tr>
		<tr>
			<td>suture line</td>
			<td>CH microsurgical instrument factory</td>
			<td>6-0/8-0</td>
			<td>high performance-price ratio</td>
		</tr>
		<tr>
			<td>topical antibodies</td>
			<td>chenxin pharmacology (www.cisen-pharma.com)</td>
			<td>H20020217</td>
			<td>Effectively avoid incision infection</td>
		</tr>
	</tbody>
</table>

a mouse model of the associating liver partition and portal vein ligation for staged hepatectomy procedure aided by microscopy

Hepatectomy is widely regarded as the primary treatment for hepatic malignancies; yet, postoperative liver failure remains a major cause of perioperative mortality, severely impacting patient outcomes. In a robust hepatic environment, the future liver remnant (FLR) must exceed 25%, and in cases of cirrhosis, this requirement increases to over 40%. The inadequacy of FLR is currently a major obstacle in the progression of hepatic surgery.
Traditional methods to enhance FLR hypertrophy mainly focus on portal vein embolization (PVE), but its effectiveness is considerably limited. In recent years, there have been numerous reports on a novel biphasic hepatectomy method involving hepatic partitioning and portal vein ligation, known as associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). ALPPS surpasses PVE in efficiently and considerably inducing FLR hypertrophy. However, the detailed mechanisms driving ALPPS-facilitated hepatic regeneration are not fully understood. Thus, replicating ALPPS in animal models is crucial to thoroughly investigate the molecular mechanisms of hepatic regeneration, offering valuable theoretical and practical insights.

Author Spotlight: Advancing Liver Regeneration Research through ALPPS Mouse Model

A Mouse Model of the Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy Procedure Aided by Microscopy

ALPPS can rapidly promote liver regeneration. However, the rather small animal model and the mechanism of the rhythm vision are still insufficient. This model allows for investigating the molecular and cellular pathway involved in liver regeneration of the severe liver injury With was the A of a ARVPS and the PMX mouse models, business studies showed that balance of PMX three and the round two in comparisons regulate haptic was killed under constitution, imposed operative liver regeneration.Single cell sequencing. Single cell attack sequencing. As well as single cell CRISPR has paved the way for the discovery of previously unknown cell types and subtypes in normal and list liver.The ARBs technique is used for patients with liver tumors that cannot be removed through surgery. The ability of the remaining liver to regenerate after the procedure is crucial for the patient's survival. However, the underlying mechanism post AFVBS remaining artery unknown.Based on the previous reports on the rat and the mouse AFVBS GECo models, we constructed a mouse GECo protocol and it was consistent with clinical operation and native limb.

In contrast to the PVL (protocol steps 2,3,4, and 5), the mice that were subjected to the ALPPS (steps 2,3,4,5, and 6) surgical intervention demonstrated a heightened proclivity towards cellular proliferation. Figure 2 delineates the ischemic demarcation of the middle liver lobe following portal vein ligation, along with the visual field during liver transection, which represents a key distinction between ALPPS and PVL. Notably, the levels of inflammatory mediators, including (Tumor Necrosis...

Read this Scientific Article Protocol about A Mouse Model of the Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy Procedure Aided by Microscopy at JoVE.com

Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) has been shown to result in remarkable liver regeneration after several weeks post first-stage surgery. Animal models that have undergone ALPPS have been developed to explore potential liver regeneration ability and achieve favorable clinical outcomes.

Hepatectomy is widely regarded as the primary treatment for hepatic malignancies; yet, postoperative liver failure remains a major cause of perioperative ...

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281 ビュー.  The First Affiliated Hospital of Nanchang Medical College. ALPPSは肝臓の再生を急速に促進することができます。しかし、やや小動物のモデルやリズム視覚のメカニズムはまだ不十分です。このモデルは、重度の肝障害の肝臓再生に関与する分子的および細胞経路を調査することを可能にします ARVPSとPMXマウスモデルのAであった、ビジネス研究は、PMX 3とラウンド2のバランスを比較して触覚を調節し、体?...