Name: Author Spotlight: Evaluating Therapeutic Strategies to Enhance Liver Regeneration
Uploaded: 2024-05-24T13:20:00
Description: Partial 2/3 hepatectomy in mice is used in research to study the liver's regenerative capacity and explore outcomes of liver resection in a number of ...

This work was supported by NIH R01 grants DK063275 and HL086741 to CF. PB and TA are recipients of an NRSA fellowship from the NHLBI T32 training grant HL007734.

The methods described within this procedure protocol have been approved by the Institutional Animal Care and Use Committee (IACUC) at the Beth Israel Deaconess Medical Center (BIDMC). All experiments were completed in accordance and compliance with IACUC and the BIDMC animal research facility guidelines.
1. Mouse preoperative preparation
<ol>
	<li>Shave the mouse abdomen from the mid-sternum to the suprapubic region with clippers.</li>
	<li>Induce general anesthesia with 1-4...

Mouse Extended Hepatectomy Model for Liver Regeneration Studies

<ol>
	<li>Martins, P. N., Theruvath, T. P., Neuhaus, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rodent+models+of+partial+hepatectomies.">Rodent models of partial hepatectomies.</a> Liver Int. 28 (1), 3-11 (2008).</li><li>Higgins, G., Anderson, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Experimental+pathology+of+the+liver+I.+Restoration+of+the+liver+of+the+white+rat+following+partial+surgical+removal.">Experimental pathology of the liver I. Restoration of the liver of the white rat following partial surgical removal.</a> Arch Pathol. 12, 186-202 (1931).</li><li>Koniaris, L. G., McKillop, I. H., Schwartz, S. I., Zimmers, T. A. <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.">Liver regeneration.</a> J Am Coll Surg. 197 (4), 634-659 (2003).</li><li>Fausto, N., Campbell, J. S., Riehle, K. J. <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.">Liver regeneration.</a> Hepatology. 43 (2), S45-S53 (2006).</li><li>Inderbitzin, D., 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=Magnetic+resonance+imaging+provides+accurate+and+precise+volume+determination+of+the+regenerating+mouse+liver.">Magnetic resonance imaging provides accurate and precise volume determination of the regenerating mouse liver.</a> J Gastrointest Surg. 8 (7), 806-811 (2004).</li><li>Clavien, P. 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=What+is+critical+for+liver+surgery+and+partial+liver+transplantation:+size+or+quality.">What is critical for liver surgery and partial liver transplantation: size or quality.</a> Hepatology. 52 (2), 715-729 (2010).</li><li>Dahm, F., Georgiev, P., Clavien, P. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Small-for-size+syndrome+after+partial+liver+transplantation:+definition,+mechanisms+of+disease+and+clinical+implications.">Small-for-size syndrome after partial liver transplantation: definition, mechanisms of disease and clinical implications.</a> Am J Transplant. 5 (11), 2605-2610 (2005).</li><li>Hori, 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=Simple+and+reproducible+hepatectomy+in+the+mouse+using+the+clip+technique.">Simple and reproducible hepatectomy in the mouse using the clip technique.</a> World J Gastroenterol. 18 (22), 2767-2774 (2012).</li><li>Kamali, C., 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=Extended+liver+resection+in+mice:+state+of+the+art+and+pitfalls-a+systematic+review.">Extended liver resection in mice: state of the art and pitfalls-a systematic review.</a> Eur J Med Res. 26 (1), 6 (2021).</li><li>Mitchell, C., Willenbring, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+reproducible+and+well-tolerated+method+for+2/3+partial+hepatectomy+in+mice.">A reproducible and well-tolerated method for 2/3 partial hepatectomy in mice.</a> Nat Protoc. 3 (7), 1167-1170 (2008).</li><li>Borowiak, 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=Met+provides+essential+signals+for+liver+regeneration.">Met provides essential signals for liver regeneration.</a> Proc Natl Acad Sci U S A. 101 (29), 10608-10613 (2004).</li><li>Boyce, S., Harrison, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+detailed+methodology+of+partial+hepatectomy+in+the+mouse.">A detailed methodology of partial hepatectomy in the mouse.</a> Lab Anim (NY). 37 (11), 529-532 (2008).</li><li>Greene, A. K., Puder, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Partial+hepatectomy+in+the+mouse:+technique+and+perioperative+management.">Partial hepatectomy in the mouse: technique and perioperative management.</a> J Invest Surg. 16 (2), 99-102 (2003).</li><li>Mitchell, C., Willenbring, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Erratum:+A+reproducible+and+well-tolerated+method+for+2/3+partial+hepatectomy+in+mice.">Erratum: A reproducible and well-tolerated method for 2/3 partial hepatectomy in mice.</a> Nat Protoc. 9 (6), 1532 (2014).</li><li>Studer, P., 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=Significant+lethality+following+liver+resection+in+A20+heterozygous+knockout+mice+uncovers+a+key+role+for+A20+in+liver+regeneration.">Significant lethality following liver resection in A20 heterozygous knockout mice uncovers a key role for A20 in liver regeneration.</a> Cell Death Differ. 22 (12), 2068-2077 (2015).</li><li>Longo, C. R., 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=A20+protects+mice+from+lethal+radical+hepatectomy+by+promoting+hepatocyte+proliferation+via+a+p21waf1-dependent+mechanism.">A20 protects mice from lethal radical hepatectomy by promoting hepatocyte proliferation via a p21waf1-dependent mechanism.</a> Hepatology. 42 (1), 156-164 (2005).</li><li>Michalopoulos, G. K., DeFrances, M. C. <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.">Liver regeneration.</a> Science. 276 (5309), 60-66 (1997).</li><li>Diehl, A. M., Rai, R. 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+regeneration.+3.+Regulation+of+signal+transduction+during+liver+regeneration.">Liver regeneration. 3. Regulation of signal transduction during liver regeneration.</a> FASEB J. 10 (2), 215-227 (1996).</li><li>. A comparison of selected organ weights and clinical pathology parameters in male and female CD-1 and CByB6F1 hybrid mice 12-14 weeks in age Available from: <a target="_blank" href="https://www.criver.com/sites/default/files/resources/doc_a/AComparisonofSelectedOrganWeightsandClinicalPathologyParametersinMaleandFemaleCD-1andCByB6F1HybridMice12-14WeeksinAge.pdf">https://www.criver.com/sites/default/files/resources/doc_a/AComparisonofSelectedOrganWeightsandClinicalPathologyParametersinMaleandFemaleCD-1andCByB6F1HybridMice12-14WeeksinAge.pdf</a> (2023)</li><li>CD-1&#174; IGS mouse. Charles River Laboratories Available from: <a target="_blank" href="https://www.criver.com/products-services/find-model/cd-1r-igs-mouse?region=3611">https://www.criver.com/products-services/find-model/cd-1r-igs-mouse?region=3611</a> (2023)</li><li>C57BL/6J mouse organ weight. The Jackson Laboratory Available from: <a target="_blank" href="https://www.jax.org/de/-/media/jaxweb/files/jax-mice-and-services/b6j-data-summary.xlsx">https://www.jax.org/de/-/media/jaxweb/files/jax-mice-and-services/b6j-data-summary.xlsx</a> (2023)</li><li>Inderbitzin, D., 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=Regenerative+capacity+of+individual+liver+lobes+in+the+microsurgical+mouse+model.">Regenerative capacity of individual liver lobes in the microsurgical mouse model.</a> Microsurgery. 26 (6), 465-469 (2006).</li><li>Zhou, X., 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=L-carnitine+promotes+liver+regeneration+after+hepatectomy+by+enhancing+lipid+metabolism.">L-carnitine promotes liver regeneration after hepatectomy by enhancing lipid metabolism.</a> J Transl Med. 21 (1), 487 (2023).</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=Omega-3+fatty+acids+protect+fatty+and+lean+mouse+livers+after+major+hepatectomy.">Omega-3 fatty acids protect fatty and lean mouse livers after major hepatectomy.</a> Ann Surg. 266 (2), 324-332 (2017).</li><li>Haber, B. 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=High+levels+of+glucose-6-phosphatase+gene+and+protein+expression+reflect+an+adaptive+response+in+proliferating+liver+and+diabetes.">High levels of glucose-6-phosphatase gene and protein expression reflect an adaptive response in proliferating liver and diabetes.</a> J Clin Invest. 95 (2), 832-841 (1995).</li><li>Rickenbacher, 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=Arguments+against+toxic+effects+of+chemotherapy+on+liver+injury+and+regeneration+in+an+experimental+model+of+partial+hepatectomy.">Arguments against toxic effects of chemotherapy on liver injury and regeneration in an experimental model of partial hepatectomy.</a> Liver Int. 31 (3), 313-321 (2011).</li><li>Aravinthan, A. D., 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=The+impact+of+preexisting+and+post-transplant+diabetes+mellitus+on+outcomes+following+liver+transplantation.">The impact of preexisting and post-transplant diabetes mellitus on outcomes following liver transplantation.</a> Transplantation. 103 (12), 2523-2530 (2019).</li><li>Gonzalez, H. D., Liu, Z. W., Cashman, S., Fusai, G. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Small+for+size+syndrome+following+living+donor+and+split+liver+transplantation.">Small for size syndrome following living donor and split liver transplantation.</a> World J Gastrointest Surg. 2 (12), 389-394 (2010).</li><li>Mahmud, N., 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+prediction+models+for+post-operative+mortality+in+patients+with+cirrhosis.">Risk prediction models for post-operative mortality in patients with cirrhosis.</a> Hepatology. 73 (1), 204-218 (2021).</li><li>Kooby, D. 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=Impact+of+steatosis+on+perioperative+outcome+following+hepatic+resection.">Impact of steatosis on perioperative outcome following hepatic resection.</a> J Gastrointest Surg. 7 (8), 1034-1044 (2003).</li><li>Ma, K., 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=A+mesenchymal-epithelial+transition+factor-agonistic+antibody+accelerates+cirrhotic+liver+regeneration+and+improves+mouse+survival+following+partial+hepatectomy.">A mesenchymal-epithelial transition factor-agonistic antibody accelerates cirrhotic liver regeneration and improves mouse survival following partial hepatectomy.</a> Liver Transpl. 28 (5), 782-793 (2022).</li><li>Hori, 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=Simple+and+sure+methodology+for+massive+hepatectomy+in+the+mouse.">Simple and sure methodology for massive hepatectomy in the mouse.</a> Ann Gastroenterol. 24 (4), 307-318 (2011).</li><li>Ramsey, H. E., 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=A20+protects+mice+from+lethal+liver+ischemia/reperfusion+injury+by+increasing+peroxisome+proliferator-activated+receptor-alpha+expression.">A20 protects mice from lethal liver ischemia/reperfusion injury by increasing peroxisome proliferator-activated receptor-alpha expression.</a> Liver Transpl. 15 (11), 1613-1621 (2009).</li><li>Arvelo, M. 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=A20+protects+mice+from+D-galactosamine/lipopolysaccharide+acute+toxic+lethal+hepatitis.">A20 protects mice from D-galactosamine/lipopolysaccharide acute toxic lethal hepatitis.</a> Hepatology. 35 (3), 535-543 (2002).</li></ol>

To successfully perform an extended 78% hepatectomy causing 50% lethality in mice, it is critical that each liver lobe is precisely resected. This level of competency and precision can only be achieved if the procedure is performed repeatedly. The training curve varies between operators but typically requires 3-6 months of practice. A liver resection that removes less than 78% of the TLM would result in higher survival rates, while a liver resection that removes greater than 78% of the TLM would result in greater lethali...

Mouse and rat surgical liver resection models, first described in 1931, are the most common experimental models utilized to study the molecular basis of liver regeneration. They could also be useful in translational science research to test and develop strategies to improve outcomes following extended liver resection or transplantation of suboptimal liver grafts1,2,3,4. Partial hepatectomies (PH) in mice entail the removal of approximately 2/3 (66%) of the total liver mass (TLM), which when performed in healthy animals have exceptional outcomes5. The procedure is short in duration, easily reproducible due to little variation in mouse liver anatomy, and postoperative survival typically nears 100%1.
Partial 2/3 hepatectomy encompassing the resection of the left lobe (LL) and median lobe (ML) allows for the residual lobes to regenerate relatively unimpeded by lobar inflammation or restriction of hepatic inflow and outflow. Rather, increased portal venous flow and subsequently shear stress on liver sinusoidal endothelial cells following PH result in sustained upregulation of endothelial nitric oxide synthase (eNOS) expression and subsequent nitric oxide (NO) release, which contribute to the priming of hepatocytes for proliferation and liver regeneration3. Outcomes commonly studied after 2/3 PH in disease models such as non-alcoholic fatty liver disease or in specific genetic backgrounds include risk of acute liver failure, qualitative and quantitative measures of the liver regenerative capacity, and other biologic responses to stress or traumatic injury1,3.
However, a mouse model mimicking functional or anatomical small-for-size syndrome, as it occurs following extended liver resection for cancer or transplantation of marginal (steatosis or prolonged ischemic time) or partial (split or from living donor liver) liver grafts, remains to be well-established. To address this need, models of more extensive liver resections that extend beyond the maintenance of a minimal (and functional) liver mass are required to model small-for-size liver syndrome and the heightened mortality that is associated with this syndrome6,7.
Mouse liver anatomy exhibits minimal variation. The mouse liver is comprised of five lobes, each accounting for the following percentage of the total liver mass: left lobe (LL; 34.4 &#177; 1.9%), median lobe (ML; 26.2 &#177; 1.9%), right upper (also called right superior) lobe (RUL; 16.6 &#177; 1.4%), right lower (also called right inferior) lobe (RLL; 14.7 &#177; 1.4%), and caudate lobe (CL, 8.1 &#177; 1.0%)1,5. Each lobe is supplied by a portal triad, including a branch of the hepatic artery, a branch of the portal vein, and a bile duct5. Historically, several techniques were described to perform a 2/3 PH by resecting the LL and the ML. These include 1) the classical technique that consists of a single ligature en bloc at the base of each of the resected lobes; 2) the hemostatic clip technique, using titanium clips applied at the base of the resected lobes; 3) a vessel-oriented parenchyma-preserving technique, using piercing sutures proximal to the clamp; and 4) a vessel-oriented microsurgical technique, whereby the portal vein and hepatic artery branches are ligated prior to lobe resection1. While each technique has relative strengths and weaknesses, none yields higher lethality1,8,9.
In this study, we present a novel method for extended 78% PH in mice. In this model, three of five liver lobes, including the LL, ML, and RUL, are removed separately using a ligature technique (Figure 1). This procedure results in the resection of approximately 78% (77.2 &#177; 5.2%) of the total liver mass. Our choice of removing the LL and ML separately, and not &#34;en bloc&#34; as in the classical PH technique, minimizes complications that are associated with en bloc resection of these two lobes, such as suprahepatic vena cava stenosis and heightened risk of necrosis of the remaining lobes when the single ligature is applied too close to the vena cava1,10,11,12,13,14. This is crucial before moving to the final step of this procedure to remove the RUL. This extensive hepatectomy in 8-12 weeks old, wild-type C57BL/6 mice causes 50% lethality within 1 week of surgery due to failed liver regeneration causing fulminant liver failure15,16. This mouse model of heightened lethality following extended 78% hepatectomy appropriately recapitulates the pathophysiology of small-for-size syndrome and enables the development and testing of novel strategies to improve outcomes.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>2 x 2 Gauze</td>
			<td>Covidien</td>
			<td>2146</td>
			<td>Surgery: dissection</td>
		</tr>
		<tr>
			<td>5-O Nylon Monofilament Suture</td>
			<td>Oasis</td>
			<td>50-118-0631</td>
			<td>Surgery: Skin closure</td>
		</tr>
		<tr>
			<td>5-O Silk Suture</td>
			<td>Fine Science Tools</td>
			<td>18020-50</td>
			<td>Surgery: liver lobe ligation</td>
		</tr>
		<tr>
			<td>5-O Vicryl Suture</td>
			<td>Ethicon</td>
			<td>NC9335902</td>
			<td>Surgery: Abdominal wall closure</td>
		</tr>
		<tr>
			<td>Addson Forceps</td>
			<td>Braintree Scientific</td>
			<td>FC028</td>
			<td>Surgery: dissection</td>
		</tr>
		<tr>
			<td>Alcohol Swabs (2)</td>
			<td>BD</td>
			<td>326895</td>
			<td>Disinfectant</td>
		</tr>
		<tr>
			<td>Buprenorphine Extended Release Formulation&#160;</td>
			<td>Zoopharm</td>
			<td>N/A</td>
			<td>Analgesia</td>
		</tr>
		<tr>
			<td>Cordless Trimmer</td>
			<td>Braintree Scientific</td>
			<td>CLP-9868-14</td>
			<td>Shaving</td>
		</tr>
		<tr>
			<td>Curved Forceps</td>
			<td>Braintree Scientific</td>
			<td>FC0038</td>
			<td>Surgery: dissection</td>
		</tr>
		<tr>
			<td>Hemostat</td>
			<td>Braintree Scientific</td>
			<td>FC79-1</td>
			<td>Surgery: dissection</td>
		</tr>
		<tr>
			<td>Isoflurane Inhalant Anesthetic&#160;</td>
			<td>Patterson Veterinary</td>
			<td>RXISO-250</td>
			<td>General Anesthesia</td>
		</tr>
		<tr>
			<td>Magnet Fixator (2-slot) (2)</td>
			<td>Braintree Scientific</td>
			<td>ACD-001</td>
			<td>Surgery: to hold small retractors</td>
		</tr>
		<tr>
			<td>Magnet Fixator (4-slot)&#160;</td>
			<td>Braintree Scientific</td>
			<td>ACD-002</td>
			<td>Surgery: to hold small retractors</td>
		</tr>
		<tr>
			<td>Microscissors</td>
			<td>Braintree Scientific</td>
			<td>SC-MI 151</td>
			<td>Surgery: dissection</td>
		</tr>
		<tr>
			<td>Operating tray</td>
			<td>Braintree Scientific</td>
			<td>ACD-0014</td>
			<td>Surgery: for establishment of surgical field&#160;</td>
		</tr>
		<tr>
			<td>Povidone Iodine 10% Swabstick (2)</td>
			<td>Medline</td>
			<td>MDS093901ZZ</td>
			<td>Disinfectant</td>
		</tr>
		<tr>
			<td>Scalpel (15-blade)</td>
			<td>Aspen Surgical Products</td>
			<td>371615</td>
			<td>Surgery: dissection</td>
		</tr>
		<tr>
			<td>Sharp Scissors (Curved)</td>
			<td>Braintree Scientific</td>
			<td>SC-T-406</td>
			<td>Surgery: dissection</td>
		</tr>
		<tr>
			<td>Sharp Scissors (Straight)</td>
			<td>Braintree Scientific</td>
			<td>SC-T-405</td>
			<td>Surgery: dissection</td>
		</tr>
		<tr>
			<td>Small Cotton-Tipped Applicators</td>
			<td>Fisher Scientific</td>
			<td>23-400-118</td>
			<td>Surgery: dissection</td>
		</tr>
		<tr>
			<td>Tissue Forceps (Straight x2)</td>
			<td>Braintree Scientific</td>
			<td>FC1001</td>
			<td>Surgery: dissection</td>
		</tr>
		<tr>
			<td>Warming Pad (18&#34; x 26&#34;)</td>
			<td>Stryker</td>
			<td>TP 700</td>
			<td>Warming</td>
		</tr>
		<tr>
			<td>Warming Pad Pump</td>
			<td>Stryker</td>
			<td>TP 700</td>
			<td>Warming</td>
		</tr>
		<tr>
			<td>Wire Handle Retractor (2)&#160;</td>
			<td>Braintree Scientific</td>
			<td>ACD-005</td>
			<td>Surgery: to facilitate exposure of peritoneal cavity</td>
		</tr>
		<tr>
			<td>Xenotec Isoflurane Small Animal Anesthesia System</td>
			<td>Braintree Scientific</td>
			<td>EZ-108SA</td>
			<td>General Anesthesia: Contains Isoflurane vaborizer &#38; console, Induction chamber, Regulator/Hose, Facemask (M)</td>
		</tr>
	</tbody>
</table>

extended 78&#37; hepatectomy in a mouse surgical model

Partial 2/3 hepatectomy in mice is used in research to study the liver's regenerative capacity and explore outcomes of liver resection in a number of disease models. In the classical partial 2/3 hepatectomy in mice, two of the five liver lobes, namely the left and median lobes representing approximately 66% of the liver mass, are resected en bloc with an expected postoperative survival of 100%. More aggressive partial hepatectomies are technically more challenging and hence, have seldom been used in mice. Our group has developed a mouse model of an extended hepatectomy technique in which three of the five liver lobes, including the left, median, and right upper lobes, are resected separately to remove approximately 78% of the total liver mass. This extended resection, in otherwise healthy mice, leaves a remnant liver that cannot always sustain adequate and timely regeneration. Failure to regenerate ultimately results in 50% postoperative lethality within 1 week due to fulminant hepatic failure. This procedure of extended 78% hepatectomy in mice represents a unique surgical model for the study of small-for-size syndrome and the evaluation of therapeutic strategies to improve liver regeneration and outcomes in the setting of liver transplantation or extended liver resection for cancer.

Author Spotlight: Evaluating Therapeutic Strategies to Enhance Liver Regeneration

Extended 78&#37; Hepatectomy in a Mouse Surgical Model

The scope of our research is to evaluate therapeutic strategies to enhance liver regeneration and repair that could aid in improving patients'outcomes in the setting of liver transplantation using marginal liver graft, as well as extended liver resection for cancer that are at higher risk for primary non-function and acute hepatic failure. Our team utilizes genomic, proteomic, and metabolomic platforms to study liver regeneration and identify novel therapeutic targets to improve outcomes. The focus of our laboratories is to develop state-of-the-art gene therapy platforms to deliver the hepatoprotective and liver regenerative gene A20.We uncovered a potent hepatoprotective function for A20, also called TNFAIP3, through its combined anti-inflammatory, anti-apoptotic, and proliferative functions in hepatocytes. Liver targeted A20 gene therapies protected from lethality in mouse models of toxic hepatitis, extended 78%and lethal radical hepatectomies 90%and also prolonged liver ischemia. Recent promising pre-translational studies in large animal prelude clinical translation of this therapy.This protocol offers a unique surgical model designed for investigating small for size syndrome, as well as assessing therapeutic strategies to improve outcomes of extensive hepatectomies for cancer, and increase successful rates of marginal and extended criteria liver grafts. When the 78%hepatectomy is performed correctly, this procedure results in approximately 50%postoperative survival as opposed to nearly 100%survival associated with the classical 2/3 partial hepatectomy in healthy mice.

A successful extended 78% hepatectomy is expected to induce 50% mortality within 1 week in healthy adult mice aged 8-12 weeks16. When properly performed, minimal blood loss is expected. Residual bleeding that persists can be controlled by manual pressure. Perioperative death within 24 h of surgery is often caused by technical errors. Technical failures include inadvertent injury to large blood vessels causing intractable intraoperative hemorrhage; significant postoperative hemorrhage often due to ...

The mouse model of partial 2/3 (66%) hepatectomy is well described in the literature, but more extended hepatectomies mimicking small-for-size syndrome after liver transplantation have seldom been used. We describe an extended 78% hepatectomy procedure in a mouse model that results in approximately 50% postoperative lethality in healthy mice.

Partial 2/3 hepatectomy in mice is used in research to study the liver's regenerative capacity and explore outcomes of liver resection in a number of ...