The University of North Carolina at Chapel Hill

Albert Einstein College of Medicine

Vertex Pharmaceuticals, Inc.

Vesta Therapeutics Inc.

Sapienza Universitá Di Roma

University of Miami-diabetes Research Institute

The University of North Carolina

Incara Cell Technologies, Inc.

Lola M Reid

Hiroshi Kubota

Eliane Wauthier

Maria Agelli

Yunfang Wang

Wencheng Zhang

Andreas Ochs

Samuel H Sigal

Shlomo Brill

Patricia A Holst

Andrew T Bruce

John W Ludlow

Mark E Furth

Randal Byrn

Luca Inverardi

Ann Kwong

Juan Dominguez-Bendala

Robert Storms

Nicholas Moss

Domenico Alvaro

Vincenzo Cardinale

Eugenio Gaudio

Guido Carpino

David A Gerber

Giacomo Lanzoni

Randall Edwin McClelland

Richard Harold Malavarca

Marsha Lynn Roach

Edward L LeCluyse

Cai-Bin Cui

Timothy Anh-Hieu Dinh

Tsunekazu Oikawa

Praveen Sethupathy

Joshua Uronis

Hsin-Lei Yao

Nicholas G Moss

Oswaldo Lozoya

Rachael Turner

David Gerber

The present disclosure provides a model of human fibrolamellar hepatocellular carcinoma (FL-HCC) cells maintained as a transplantable tumor line in a host and a method to establish a transplantable human FL-HCC tumor line. Methods of ex vivo cultures of the FL-HCC are provided. Methods of diagnosing and treating FL-HCC tumors are also provided.

Human fibrolamellar hepatocellular carcinomas (hFL-HCCs)

Compositions and methods of transplanting cells by grafting strategies into solid organs (especially internal organs) are provided. These methods and compositions can be used to repair diseased organs or to establish models of disease states in experimental hosts. The method involves attachment onto the surface of a tissue or organ, a patch graft, a 'bandaid-like' covering, containing epithelial cells with supporting early lineage stage mesenchymal cells. The cells are incorporated into soft gel-forming biomaterials prepared under serum-free, defined conditions comprised of nutrients, lipids, vitamins, and regulatory signals that collectively support stemness of the donor cells. The graft is covered with a biodegradable, biocompatible, bioresorbable backing used to affix the graft to the target site. The cells in the graft migrate into and throughout the tissue such that within a couple of weeks they are uniformly dispersed within the recipient (host) tissue. The mechanisms by which engraftment and integration of donor cells into the organ or tissue involve multiple membrane-associated and secreted forms of MMPs.

Patch graft compositions for cell engraftment

The present invention provides biomatrix scaffolds for industrial scale dispersal.

Biomatrix scaffolds for industrial scale dispersal

The present invention relates to precursor cells to hepatic stellate cells, compositions comprising same and methods of isolating same. The surface antigenic profile of the precursors is MHC class Ia negative, ICAM-1, VCAM-1, &#x3b2;3-integrin. In addition to expression of these surface markers, the cells also express the intracellular markers desmin, vimentin, smooth muscle &#x3b1;-actin, nestin, hepatocyte growth factor, stromal derived factor-1&#x3b1; and Hlx homeobox transcriptional factor.

Hepatic stellate cell precursors and methods of isolating same

A method of repairing diseased or dysfunctional pancreas or liver is provided. The method involves preparation of a suspension of stem cells and/or progenitor cells such as biliary tree stem cells, hepatic stem cells, pancreatic stem cells or their descendants, committed progenitor cells, from healthy tissue of the patient or of the biliary tree of a non-autologous donor and engrafting the cells into the wall of bile ducts near to the organ to be treated. The graft consists of stem cells or progenitors that are admixed with biomaterials and, optionally, with cytokines and/or native epithelial-mesenchymal cells appropriate for the maturational lineage stage of the cells to be engrafted. The cells are specifically introduced to the hepato-pancreatic common duct of the subject for treatment of pancreatic conditions or to the bile duct wall near to the liver for treatment of liver conditions and allowed to migrate to the pancreas or to the liver and expand and then rebuild part or the entirety of the diseased or dysfunctional organ.

Method of treating pancreatic and liver conditions by endoscopic-mediated (or laparoscopic-mediated) transplantation of stem cells into/onto bile duct walls of particular regions of the biliary tree

A method of obtaining a mixture of cells enriched in hepatic progenitors is developed which comprises methods yielding suspensions of a mixture of cell types, and selecting those cells that are classical MHC class I antigen(s) negative and ICAM-1 antigen positive. The weak or dull expression of nonclassical MHC class I antigen(s) can be used for further enrichment of hepatic progenitors. Furthermore, the progenitors can be selected to have a level of side scatter, a measure of granularity or cytoplasmic droplets, that is higher than that in non-parenchymal cells, such as hemopoietic cells, and lower than that in mature parenchymal cells, such as hepatocytes. Furthermore, the progeny of the isolated progenitors can express alpha-fetoprotein and/or albumin and/or CK19. The hepatic progenitors, so isolated, can grow clonally, that is an entire population of progeny can be derived from one cell. The clones of progenitors have a growth pattern in culture of piled-up aggregates or clusters. These methods of isolating the hepatic progenitors are applicable to any vertebrates including human. The hepatic progenitor cell population is expected to be useful for cell therapies, for bioartificial livers, for gene therapies, for vaccine development, and for myriad toxicological, pharmacological, and pharmaceutical programs and investigations.

Methods of isolating bipotent hepatic progenitor cells

Hepatic progenitors comprise two populations of human hepatic stem cells, primitive and proximal hepatic stem cells, and two populations of committed progenitors, one for biliary cells and one for hepatocytes. Human primitive hepatic stem cells are a very small fraction of the liver cell population and give rise to proximal hepatic stem cells constituting a much larger fraction of the liver. Human proximal hepatic stem cells give rise to biliary and hepatocyte committed progenitors. Primitive and proximal stem cells are the primary stem cells for the human liver. Human primitive hepatic stem cells may be isolated by immunoselection from human livers or culturing human liver cells under conditions which select for a human primitive hepatic stem cell. Proximal hepatic stem cells may be isolated by immunoselection, or by culturing human liver cells under conditions which include a developmental factor. Proximal hepatic stem cells may also be isolated by culturing colonies comprising a primitive hepatic stem cell under conditions which include a developmental factor. Resulting compositions may be used for treating liver disorders and for producing bioartificial organs.

Primitive and proximal hepatic stem cells

A method is provided for controlling the survival, proliferation, and/or differentiation of hepatic progenitors in vitro by using specific types of mesenchymal feeder cells or one of more of the paracrine signals produced by those feeders.

Paracrine signals from mesenchymal feeder cells and regulating expansion and differentiation of hepatic progenitors using same

The present invention provides compositions comprising cells that can effectively produce HCV after HCV infection, compositions for culturing the cells, methods for making the composition and methods for infecting the cells in the composition with HCV. The present invention also provides methods for assaying HCV production and methods for evaluating compounds that affect the production of HCV.

Method useful for HCV RNA898 infection

Growing community of inventors

Chapel Hill, NC, United States of America

Lola M Reid