Lab-grown embryo models mimic natural formation of blood and heart cells

University of Cambridge scientists have used human stem cells to create three-dimensional embryo-like structures that replicate certain aspects of very early human development - including the production of blood stem cells.

Human blood stem cells, also known as hematopoietic stem cells, are immature cells that can develop into any type of blood cell, including red blood cells that carry oxygen and various types of white blood cells crucial to the immune system.

The embryo-like structures, which the scientists have named 'hematoids', are self-organising and start producing blood after around two weeks of development in the lab - mimicking the development process in human embryos.

The structures differ from real human embryos in many ways, and cannot develop into them because they lack several embryonic tissues, as well as the supporting yolk sac and placenta needed for further development.

Hematoids hold exciting potential for a better understanding of blood formation during early human development, simulating blood disorders like leukaemia, and for producing long-lasting blood stem cells for transplants.

The human stem cells used to derive hematoids can be created from any cell in the body. This means the approach also holds great potential for personalized medicine in the future, by allowing the production of blood that is fully compatible with a patient's own body.

Although other methods exist for generating human blood stem cells in the laboratory, these require a cocktail of extra proteins to support the stem cells' growth and development. The new method mimics the natural developmental process, based on a self-organising human embryo-like model, where the cells' intrinsic support environment drives the formation of blood cells and beating heart cells within the same system.

The findings are published today in the journal Cell Reports.

It was an exciting moment when the blood red colour appeared in the dish – it was visible even to the naked eye.

Our new model mimics human fetal 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 leukemia."

Dr. Jitesh Neupane, researcher at the University of Cambridge's Gurdon Institute and first author of the study

Professor Azim Surani at the University of Cambridge's Gurdon Institute, senior author of the paper, said: "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."

Dr Geraldine Jowett at the University of Cambridge's Gurdon Institute, a co-first author of the study, said: "Hematoids capture the second wave of blood development that can give rise to specialised immune cells or adaptive lymphoid cells, like T cells opening up exciting avenues for their use in modelling healthy and cancerous blood development."

Self-organizing structures

The new human embryo-like model simulates the cell changes that occur during the very early stages of human development, when our organs and blood system first begin to form.

The team observed the emergence of the three-dimensional hematoids under a microscope in the lab. By the second day, these had self-organised into three germ layers - called the ectoderm, mesoderm, and endoderm - the foundations of the human body plan that are crucial for shaping every organ and tissue, including blood.

By day eight, beating heart cells had formed. These cells eventually give rise to the heart in a developing human embryo.

By day thirteen, the team saw red patches of blood appearing in the hematoids. They also developed a method which demonstrated that blood stem cells in hematoids can differentiate into various blood cell types, including specialised immune cells, such as T-cells.

Shining a light on early human development

Stem cell-derived embryo models are crucial for advancing our knowledge of early human development.

The blood cells in hematoids develop to a stage that roughly corresponds to week four to five of human embryonic development. This very early stage of life cannot be directly observed in a real human embryo because it has implanted in the mother's womb by this time.

There are clear regulations governing stem cell-based models of human embryos, and all research modelling human embryo development must be approved by ethics committees before proceeding. This study received the necessary approvals, and the resulting paper has been peer reviewed.

The scientists have patented this work through Cambridge Enterprise, the innovation arm of the University of Cambridge, which helps researchers translate their work into a globally leading economic and social impact.