Geron Corporation

Asterias Biotherapeutics, Inc.

Ramkumar Mandalam

Melissa K Carpenter

Chunhui Xu

Joseph D Gold

Yan Li

Jane S Lebkowski

Lakshmi Rambhatla

Choy-Pik Chiu

Kristina Pfendler-Bonham

Namitha Rao

Isabelle Nadeau

Saadia Faouzi

Isabelle Nadeau-Demers

Ralph Brandenberger

Lawrence W Stanton

John M Irving

Michael Mok

Yian Li

This disclosure provides an improved system for culturing human embryonic stem cells. The cells are cultured in suspension so as to maximize the production capacity of the culture environment. The new culture system of this invention allows for bulk proliferation of hES cells in a more cost-effective manner, which facilitates commercial production of important products for use in human therapy.

Suspension culture of human embryonic stem cells

This disclosure provides an improved system for culturing human pluripotent stem cells. Traditionally, pluripotent stem cells are cultured on a layer of feeder cells (such as mouse embryonic fibroblasts) to prevent them from differentiating. In the system described here, the role of feeder cells is replaced by components added to the culture environment that support rapid proliferation without differentiation. Effective features are a suitable support structure for the cells, and an effective medium that can be added fresh to the culture without being preconditioned by another cell type. Culturing human embryonic stem cells in fresh medium according to this invention causes the cells to expand surprisingly rapidly, while retaining the ability to differentiate into cells representing all three embryonic germ layers. This new culture system allows for bulk proliferation of pPS cells for commercial production of important products for use in drug screening and human therapy.

Screening methods for human embryonic stem cells

This disclosure provides a newly developed strategy and particular options for differentiating pluripotent stem cells into cells of the hepatocyte lineage. Many of the protocols are based on a strategy in which the cells are first differentiated into early germ layer cells, then into hepatocyte precursors, and then into mature cells. The cells obtained have morphological features and phenotypic markers characteristic of human adult hepatocytes. They also show evidence of cytochrome p450 enzyme activity, validating their utility for commercial applications such as drug screening, or use in the manufacture of medicaments and medical devices for clinical therapy.

Protocols for making hepatocytes from embryonic stem cells

Primate pluripotent stem cell expansion without feeder cells and in the presence of FGF and matrigel or Engelbreth-Holm-Swarm tumor cell preparation

Human embryonic stem cells genetically modified to contain a nucleic acid and cultured with fibroblast growth factor

Micro-carrier culture system for rapid expansion of human embryonic stem cells

This disclosure provides an improved system for culturing human pluripotent stem cells. Traditionally, pluripotent stem cells are cultured on a layer of mouse embryonic fibroblast feeder cells to prevent them from differentiating. In the system described here, the role of feeder cells is replaced by defined components added to the culture environment that support rapid proliferation without differentiation. The medium contains an isotonic buffer, a blend of essential nutrients such as protein and lipids, and an effective growth factor or combination of factors that promote proliferation while inhibiting differentiation. Culturing human embryonic stem cells in fresh medium on an extracellular matrix according to this invention causes the cells to expand surprisingly rapidly, while retaining the ability to differentiate into cells representing all three embryonic germ layers. This new culture system allows for bulk proliferation of pPS cells for commercial production of important products for use in drug screening and human therapy.

Medium for growing human embryonic stem cells

Culture system for rapid expansion of human embryonic stem cells

This disclosure provides a system for qualifying embryonic stem cells intended for human therapy. A large-scale sequencing project has identified important markers that are characteristic of undifferentiated pluripotent cells. Combinations of these markers can be used to validate the self-renewing capacity of ES cells, and their ability to differentiate into tissue types suitable for regenerative medicine. The marker system of this invention has been used to screen feeder cells, media additives, and culture conditions that promote proliferation of stem cells without differentiation. A culture system optimized by following these markers is suitable for rapid expansion of undifferentiated cells from existing lines, or the derivation of new lines that are equally apposite for clinical use.

Marker system for preparing and characterizing high-quality human embryonic stem cells

Growing community of inventors

Union City, CA, United States of America

Ramkumar Mandalam