Melbourne, Australia continues to grow as a hub of drug discovery and development R&D with a Murdoch Children’s Research Institute-based team announcing that they have reproduced and visualized the earliest developmental steps in human immune cell production in the laboratory Down Under. The team’s bold agenda is to advance our collective understanding of childhood diseases, such as leukemia and autoimmune disorders. The vision: One day a patient’s own skin cells could be used to produce new cells for cancer immunotherapy or to test autoimmune disease interventions.

The study Multipotent RAG1+ progenitors emerge directly from haemogenic endothelium in human pluripotent stem cell-derived haematopoietic organoids was published in Nature Cell Biology.

The Research

The team, led by Professors Ed Stanley and Andrew Elefanty from Melbourne’s Murdoch Children’s Research Institute have identified evidence as to how the human body forms immune cells.  According to the recent Murdoch Children’s Research Institute (MCRI) press release, the breakthrough involves lymphocytes that are produced by cells that form the embryo’s first organs—rather than in the blood-producing stem cells that exist in bone marrow.

The Methods to the Breakthrough

The team used two powerful research techniques, including 1) genetic engineering and 2) a novel method to grow stem cells to enable the ability to collect the data and undertake the analysis, which led to the actual declared results.

The Steps

First, the team engineered pluripotent stem cells to glow green when a specific protein marker of early immune cells, RAG1, was switched on. RAG1 is responsible for creating the immune response to infections and vaccines. Second, the team isolated the glowing green RAG1-positive cells and demonstrated that they could also form multiple immune cell types—such as cells required for shaping the entire immune system.

Research Comments

Professor Stanley commented, “We think these early cells might be important for the correct maturation of the thymus, the organ that acts as a nursery for T-cells.”

Funders

·         National Health and Medical Research Council

·         Australian Research Council

·         The Children’s Cancer Research Foundation (Australia)

·         Stafford Fox Medical Research Foundation

·         Researchers from University of Melbourne, Monash University and the Walter Eliza Hall Institute)

Lead Research/Investigator

Ed Stanley 

Andrew Elefanty 

Call to Action: Professor Elefanty reminds us that a clinical application is still years away but early-stage researchers can leverage this knowledge to investigate ideas about how diseases like childhood leukemia and type 1 diabetes develop. As we develop knowledge as to the “steps these cells go through, and how we can officially nudge them down a desire pathway,” the potential for transformative therapies in these therapeutic areas become possible.

Source: Murdoch Children's Research Institute

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