HEPATIC STELLATE CELLS
Hepatic stellate cells (HSCs) — also called interstitial cells, fat-storing cells, Vitamin A-storing cells, or Ito cells — are perisinusoidal cells distributed throughout the liver, located in the space of Disse between the hepatocytes and sinusoidal endothelial cells. The stellate cells arise embryologically from the septum transversum mesenchyme from precursor cells that invade the liver parenchyma from the hepatic capsule. In the normal adult liver, these important cells store retinoids as retinyl palmitate in cytoplasmic lipid droplets and are pivotal in the regulation of retinoid homeostasis. Other functions ascribed to hepatic stellate cells include vasoregulation (through interactions with endothelial cells), extracellular matrix homeostasis, immune regulation, drug detoxification, and production of mitogens and morphogens (such as hepatocyte growth factor) that serve to preserve and/or restore hepatocyte mass.
Under physiological conditions, HSCs exhibit a quiescent phenotype (qHSCs). They express neural markers, such as GFAP, synemin, synaptophysin, and nerve growth factor receptor p75 and store vitamin A in lipid droplets. In response to liver injury, such as chronic exposure to certain drugs or chemicals, steatosis, and/or persistent inflammation, qHSCs decrease vitamin A storage and peroxisome proliferator-activated receptor (PPAR) expression, and activate into collagen type I and αSMA expressing myofibroblasts (aHSCs). Persistent activation of HSCs and intrahepatic presence of myofibroblasts leads to fibrosis, portal hypertension, and cirrhosis, thus aHSCs are the primary target for anti-fibrosis therapies. Active areas of research involving stellate cells are broad, and include mechanisms of activation, fibrosis and resolution of fibrosis, inflammation, regeneration, and the development of hepatocellular cancer.
In vitro monolayer culture of hepatic stellate cells typically results in the development of a culture-activated phenotype, with progressive increases in expression of αSMA and loss of phenotypic features associated with quiescence, including lipid droplets and expression of GFAP. However, study results have suggested that culture-activated stellate cells may re-gain a quiescent phenotype when implanted into the in vivo microenvironment1, 2 or incorporated into multicellular 3D tissues comprising other liver cell types3, 4. Click here to download a general product information sheet.
Kupffer cells are the resident macrophages in the liver and are involved in normal physiology and homeostasis as well as mediating response to toxic injury and disease. When Kupffer cells are activated, they release cytokines, growth factors, and reactive oxygen species, all of which can have acute effects on hepatocytes and other cell types. Persistent activation of Kupffer cells may contribute to chronic disease processes, including chronic drug-induced liver injury, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatotic hepatitis (NASH), alcoholic steatohepatitis, and hepatic cancer. Within the liver, the mobile Kupffer cells are able to traverse the sinusoidal endothelial barrier and interact with cells and signals present in the sinusoidal blood flow and in the space of Disse between the sinusoidal endothelial cells and hepatocytes. Both phagocytosis and inducible cytokine release are considered important functional measures of Kupffer cells. Marker expression may vary in human Kupffer cells depending on activation state, but generally includes significant populations of cells that are immunopositive for CD11b and CD68. Click here to download a general product information sheet. Available Kupffer Cells (KC) lots can be found in the Liver Cell Inventory Table.
LIVER-DERIVED ENDOTHELIAL CELLS
Samsara’s primary liver-derived endothelial cells (LEC) are isolated by elutriation and are comprised of cells that express general endothelial cell markers, such as CD31 and von Willebrand Factor (vWF) and more specific sinusoidal endothelial cell-associated markers, such as CD32b and LYVE-1. Liver-derived endothelial cells may be important components of co-culture or 3D tissue systems, due to their highly specialized, tissue-specific nature. Samsara’s LEC are capable of tube formation in vitro and can be propagated through limited serial passage for use in assays. Click here to download a general product information sheet. Available LEC lots can be found in the Liver Cell Inventory Table.
|Lot ID||LIVER PATHOLOGY||DONOR AGE / GENDER||BMI||DONOR MORBIDITIES||NORMAL|
(GRADE 0 STEATOSIS)
|GRADE 1 STEATOSIS||GRADE 2 STEATOSIS||GRADE 3 STEATOSIS||INVENTORY|
|Inflammation Grade*||Fibrosis Score*||NAFLD|
|Inflammation Grade*||Fibrosis Score*||NAFLD|
|Inflammation Grade*||Fibrosis Score*||NAFLD|
|Inflammation Grade*||Fibrosis Score*||NAFLD
|HL160016||Near normal||0.66 / M||12.8||Muscular Dystrophy||0||0||0||FFPE, LEC|
|HL160018||Near normal||35 / F||24.7||None||0||0||0||FFPE, SFT|
|24 / M||22.9||None||0-1||0||0||FFPE, SC|
|HL160026||Near normal||25 / F||26||Pulmonary Arterial Hypertension Lung Transplant||0||0||0||FFPE, SFT, SCp2|
|HL160033||Near normal||22 / M||29.1||Acute Drug Toxicity, Metabolic acidosis||0||0||0||FFPE, SFT|
|HL170057||Near normal||35 / F||22.2||Anoxia / drowning||0||0||0||FFPE, SFT, LEC, HCP|
|HL170063||Near normal||59 / F||27.4||ICH / Stroke||0||0||0||FFPE, SFT, SC, KC, LEC, HCS|
|HL180067||Near normal||12 / M||17.7||Head trauma||0||0||0||FFPE, SFT, SC, KC, LEC|
|HL180070||Near normal||52 / F||35.4||ICH / Stroke||0||0||0||FFPE, SFT, SC, KC, LEC, HCS|
|HL170044||Near Normal, minimal periportal inflammation||47 / M||32.9||Anoxia||0-1||0||0||FFPE, SFT, SC, LEC, HCS|
|HL150004||Near normal, ductal plate malformation||54 / M||32||None||1||1||0||FFPE, SC|
|HL150006||Near Normal, Vascular outflow defect||31 / F||28.7||Sepsis (confirmed)||1||0||0||FFPE|
|HL150008||Near normal||59 / M||34||None||1||0||0-1||FFPE, SFT, SC|
|HL150010||Inflammmation (mild)||69 / M||21||Diabetes (Type 2), Hypertension, Renal Failure||1||0||0||FFPE, SFT, SC|
|43 / M||23.8||None||1||0||0||FFPE, SFT, SC|
|HL160023||Inflammation (mild, chronic), bile duct|
|57 / M||27||Diabetes (Type 2) Hypertension||1||0||0||FFPE, SFT, SC|
|57 / F||35.2||Cardiac Arrest/ Anoxia||1||0||0||FFPE, SFT, HCS , LEC, SC, KC|
|HL160036||Inflammation (mild)||25 / M||30.8||Acute Drug Toxicity||0-1||0||0||FFPE, SFT, SC, EC|
|HL160038||Minimal portal inflammation||23 / M||30.56||Head Trauma / GSW||1||0||0||SC, LEC|
|HL170047||No steatohepatitis, Very mild portal inflammation.||34 / M||23||Anoxia/ respiratory failure||1||0||0||FFPE, SFT, SC, LEC,HCS|
|HL170062||Minimal portal, focal periductal fibrosis||79 / F||27.8||ICH / Stroke||1||0||0||FFPE, SFT, KC, LEC, HC|
|HL160037||Inflammation (mild, portal)||47 / F||34.6||Hypertension||1||0||0-1||FFPE, SFT, HCS , LEC|
|HL170051||Minimal portal inflammation||64 / M||37.2||GERD, Depression, Orchidectomy for testicular cancer (2002 cured)||1||0||1||FFPE, SFT, HCP, SC, LEC|
|HL180068||Minimal steatosis||59 / F||36.2||Anoxia / Cardiac arrest||1||0||1||FFPE, SFT, SC, KC, LEC|
|HL170052||Peri-portal iron with stage 0-1 fibrosis, minimal portal inflammation||29 / M||23.1||Chronic alcoholism||1||0-1||1||FFPE, SFT, LEC|
|HL160031||Inflammation (mild), oxidative/toxic injury, fibrosis||42 / M||24.1||GERD||1||2||0||FFPE, SFT, SC, HCP|
|HL160025||Inflammation (mild), glycogen accumulation||70 / M||25.6||None||1-2||0||0||FFPE, SFT, SC, HCP , LEC|
|HL160019||Inflammation (mild)||53 / M||25.3||None||1-2||0||0||FFPE, SFT, LEC|
|42 / M||Hypertension||2||0||0||FFPE, SFT|
|HL150001||Steatosis||47 / M||27.1||Diabetes (Type 2)||0||0||1||FFPE, SFT|
|HL150007||peri-portal small droplet fat||29 / M||23.1||Head trauma/MVA||0||0||1||FFPE, SFT|
|HL160024||Inflammation (chronic), Sepsis (possible), biliary|
|62 / M||35.2||Diabetes (Type 2), Hypertension, Gout||2||0||1||FFPE, SFT, SC, HCP , LEC|
|37 / M||29.4||Chronic drug exposure||0||0||2||FFPE|
|HL160027||Steatosis||26 / M||24.8||None||1||0||2||FFPE, SFT, SC|
|HL160017||Steatosis, cholangitis, fibrosis||31 / M||24.7||Chronic Alcoholism, Hypertension||1||2||2||FFPE, SFT, SC, LEC|
|HL170053||Mild portal inflammation. Very mild steatohepatitis.||62 / M||33.4||Hypertension, Hyperlipidemia, stent placement||1||0||3||FFPE, HCP, SC, LEC|
|HL150013||Steatosis, inflammation, fibrosis||45 / M||35||Diabetes (Type 2),|
|HL160014||Cirrhosis, steatosis, inflammation (chronic)||60 / M||23.1||Hypertension||3||4||ASH||FFPE, SFT|
|HL160030||Steatosis||29 / M||30.2||Diabetes (type 2), Hypertension, Asthma||0||0||2||FFPE, SFT|
|HL180069||No fibrosis, no steatohepatitis||22 / M||23.2||Head Trauma / MVA||0||0||2||FFPE, SFT, SC, KC, LEC|
|HL160032||Inflammation (mild), Steatosis||23 / M||29.4||None reported||1||0||2||FFPE, SFT, KC, LEC|
|HL160015||Steatosis, fibrosis||59 / M||28.1||Hypertension, Hyperlipidemia||1||1a||3||FFPE, SFT|
|HL170046||53 / F||48.06||Cardiac Arrest/ Anoxia||1||1a||3||FFPE, SFT, SC, KC, LEC, HCS|
|HL170048||Minimally active steatohepatitis||48 / F||32||Cardiac Arrest/ Anoxia||1||1||3||FFPE, SFT, SC, KC, LEC, HCS|
|HL170058||Chronic steatohepatitis, but not active||58 / F||38.3||CVA/ Stroke||1||2||3||FFPE, SFT, SC, LEC, HCS|
|HL170065||Hypertension, CHF, CHD, COPD||57 / F||60.6||Anoxia/Cardiac Arrest, Type II Diabetes||1-2||0||4||FFPE, SFT, SC, LEC, HCS|
|HL170064||lobular inflammation and mild fibrosis||66 / M||37||Cardiac Arrest/ Anoxia||2||1||5||FFPE, SFT, SC, LEC, HCS|
|HL180071||No active steatohepatitis||52 / F||44.4||ICH/ Stroke||1||0||4||FFPE, SFT, SC, KC, LEC, HCP|
|HL170059||Chronic steatohepatitis with 1C fibrosis||67 / F||37.5||ICH / Stroke||0-1||1||4||FFPE, SFT, KC, LEC, HCS|
|HL160021||Steatohepatitis (chronic, active), fibrosis||44 / F||34.5||Diabetes (Type 2), Chronic Kidney Disease||1||1a||4||FFPE, SFT, SC|
|HL160022||Steatohepatitis (chronic, active),|
|45 / F||29.8||Epilepsy||1||2||5||FFPE, SFT|
|HL170049||Cirrhosis, steatohepatitis||34 / F||23.8||Anoxia / seizure||1||4||ASH||FFPE, SFT, SC, KC, LEC|
|HL170066||Hypertension, kidney stones||51 / M||37.7||ICH / Stroke||2||2||6||FFPE, SFT, SC, LEC, HC|
|HL160041||Steatohepatitis, fibrosis, ascending cholangitis, possible drug injury||33 / M||35.4||None reported||2||2||ASH||FFPE, SFT|
All histopathology assessment conducted by board certified liver pathologist and scored according to standard clinical practice.
*Inflammation and fibrosis were assessed using standard Batts-Ludwig scoring methodology (Scale, 0-4).
**NAFLD score (NAS) was assigned according to the standards of the NASH CRN Scoring System (Hepatology 2005; 41:1313-1321).
- Crespo Yanguas, S., et al., Experimental models of liver fibrosis. Arch Toxicol, 2015.
- Dusabineza, A.C., et al., Hepatic stellate cells improve engraftment of human primary hepatocytes: A pre-clinical transplantation study in animal model. Cell Transplant, 2015.
- Robbins, J., et al., Bioprinted Human Liver Tissue With iPSC-Derived Hepatocyte-Like Cells 2013: Boston. View SCOM Poster
- Roskos, K., S. Pentoney, and S. Presnell, Bioprinting: An Industrial Perspective, in Essentials of 3D Biofabrication and Translation, J. Yoo and A. Atala, Editors. 2015, Elsevier: Academic Press.