Human blood stem cells successfully grown in vitro

Human stem cells, of the type that are used for blood stem cell transplants, have been grown in a bioengineered gel designed to mimic the bone marrow. 

Researchers at the University of Glasgow have developed a method of culturing a specific type of human stem cell found in the bone marrow, known as long-term haematopoietic stem cells, in a jelly-like gel which better mimics their natural microenvironment. This encourages the long-term haematopoietic stem cells to replicate, rather than differentiate to other cell types or die, potentially providing a source of cells for drug testing and treatments for blood disorders, including leukaemia. 

Dr Hannah Donnelly, the research fellow who led the study at the University of Glasgow said: 'Long-term haematopoietic stem cells are notoriously difficult to culture outside the body yet hold enormous clinical value. Here, we show that by using gels engineered to mimic the environment where they reside in the bone marrow, we can support and study these cells in the lab, ultimately harnessing their full clinical potential.'

Stem cell transplants can be used to treat a range of blood disorders, including leukaemia and sickle cell disease. This requires the patient's bone marrow stem cells to be depleted using chemotherapy, followed by replacement with immunologically matched donor cells. However, there is currently a greater clinical demand than can be fulfilled.

One of the major difficulties is that the long-term haematopoietic stem cells most crucial for ensuring long-term donor cell engraftment represent a tiny percentage of the bone marrow cell population. Therefore, having a robust method of expanding these cells outside of the body could increase the number of successful transplantations.

This research, published in Nature Communications, has used bioengineering methods to generate a gel to culture and expand long-term haematopoietic stem cells for longer periods of time. Engineering of this gel required multiple elements of the bone marrow microenvironment to be replicated to maintain the key properties of the long-term haematopoietic stem cells, including the softness of the gel, concentrations of numerous signalling factors and the presence of other supporting cell types.

The group has also shown that the long-term haematopoietic stem cells cultured using their gel can be genome-edited using CRISPR. This could help researchers to further study the cells and test new treatments for blood disorders in a way that avoids having to use animal models.

Professor Manuel Salmeron Sanchez, chair of biomedical engineering and head of the School of Engineering at the University of Glasgow, added: 'This work is tremendously exciting. Currently, a major problem is that we rely on non-human rodent models to understand disease progression and to identify new treatments. By developing a new model such as we have done in this study, which mimics the bone marrow, and by using human cells within these models, we can focus on these earliest stages of diseases to provide new understanding, new screening methods and new drugs.'