Researchers have developed new laboratory models and machine learning systems that simulate early human and embryonic development. University of Cambridge scientists created self-organizing ‘hematoids’ that produce blood cells, while researchers led by Whitehead Institute member Pulin Li and graduate student Nicholas Hutchins built an AI model named IRIS to decode embryonic signaling pathways.
Lab-Grown Hematoids Produce Early Human Blood Cells
Scientists at the University of Cambridge have used human stem cells to produce three-dimensional embryo-like structures that replicate early human development, including the formation of blood stem cells. These self-organizing structures, named hematoids
, begin producing blood after roughly two weeks in the lab according to University of Cambridge researchers.
The human stem cells used to derive hematoids can be created from any cell in the body. This approach offers potential for personalized medicine by allowing the production of blood that is fully compatible with a patient's own body. Unlike other laboratory methods that require a cocktail of extra proteins to support stem cell growth, the new method relies on an intrinsic support environment.
"It was an exciting moment when the blood red colour appeared in the dish – it was visible even to the naked eye."
Dr Jitesh Neupane, University of Cambridge's Gurdon Institute
The research team observed the emergence of the structures under a microscope. By the second day, the cells had self-organized into three germ layers—the ectoderm, mesoderm, and endoderm. By day eight, beating heart cells had formed, and by day thirteen, red patches of blood appeared in the hematoids as detailed by the Cambridge research team.
Visualizing Early Stages That Cannot Be Directly Observed
Stem cell-derived embryo models help advance knowledge of early human development. The blood cells in hematoids develop to a stage corresponding roughly to week four to five of human embryonic development, a timeframe that cannot be directly observed in a real human embryo because implantation has already occurred by that stage.
"Our new model mimics human foetal blood development in the lab. This sheds light on how blood cells naturally form during human embryogenesis, offering potential medical advances to screen drugs, study early blood and immune development, and model blood disorders like leukaemia."
Dr Jitesh Neupane, University of Cambridge's Gurdon Institute
Researchers note that hematoids capture the second wave of blood development capable of giving rise to specialized immune cells or adaptive lymphoid cells, such as T cells. The models differ from real human embryos and cannot develop into them because they lack several embryonic tissues, as well as the supporting yolk sac and placenta.
IRIS Machine Learning Model Decodes Embryonic Signaling
The neural network-based system detects fingerprints of different signaling pathways to pinpoint which chemical signals a cell received at different stages of embryonic development.
Scientists previously assumed that the effects of signaling pathways varied widely across cell types, requiring researchers to map each pathway separately in every cell type. The new study found that each signaling pathway leaves behind a consistent fingerprint of gene activity across different cell types.
"This model offers a powerful new way to study blood development in the early human embryo. Although it is still in the early stages, the ability to produce human blood cells in the lab marks a significant step towards future regenerative therapies – which use a patient’s own cells to repair and regenerate damaged tissues."
Professor Azim Surani, University of Cambridge's Gurdon Institute
Neural Developmental Modeling and FGF2 Signaling
Investigators validated human pluripotent stem cell-based systems by comparing them with neural developmental events in mice.
The study found that the human pluripotent stem cell-based system mimicked the transition from the neural plate to the neural tube, and subsequently to the neocortex, while capturing key characteristics of brain development. The system also preserved a neural stem cell niche residing in the ventricular region of the cortex, with FGF2 signaling exhibiting varying regulatory activities across neural stages.
