Bioprocess for producing uniform embryoid bodies from embryonic stem cells in a high density bioreactor

A bioprocess for controlling aggregation of embryoid bodies during differentiation, comprising:

• a) monitoring E-cadherin expression over time in a differentiating embryoid body;
• b) determining a time when E-cadherin is down-regulated sufficiently in said embryoid body to prevent aggregation of embryoid bodies;
• c) encapsulating one or more embryonic stem cells expressing E-cadherin in a biodegradable matrix so as to form a cell capsule, wherein the capsule is of a size to enable an embryoid body formed within the capsule to emerge from the capsule after down regulation of E-cadherin;
• d) introducing the encapsulated cells into a cell culture environment comprising cell culture media, growth factors, and other factors to promote cell growth;
• e) culturing the encapsulated cells from d) so as to form an embryoid body, said culturing being for a time as determined in b), such that the embryoid body formed within the capsule will emerge from the capsule and will not aggregate with other embryoid bodies upon emergence from the capsule;
• f) optionally harvesting differentiated cells derived from the embryoid body that emerged from the capsule from the culture in step e).