For patients suffering from leukemia, multiple myeloma or different types of infections, bone marrow transplants represent life-saving procedures. After radiation or chemotherapy, doctors are able to “reset” their immune system by infusing blood stem cells from a matched donor. This form of treatment presents many risks and initially leaves them with a reduced ability to generate T-cells and can cause long-lasting post-transplant immune deficiency, increasing the threat of opportunistic infectious diseases and immunological complications such as graft-versus-host-disease.
Harvard engineers working with stem cell biologists have designed an injectable sponge-like gel that boosts T-cells production after a bone marrow transplant, increasing the quantity and diversity of these essential components. The device is meant to be injected under the skin at the same time as the transplant to help revive the immune system after surgery.
“T-cell deficiency and dysfunction is a life-threatening challenge, especially in transplant settings”, explained co-senior author David Scadden, Professor of Medicine and Co-Director of the Harvard Stem Cell Institute. “Our research demonstrates a simple to administer, off-the-shelf solution that can enhance T-cell regeneration after stem cell transplantation”.
Previous solutions mainly focused on improving the function of the thymus, where the T cells are produced. This new method looks to expand the cells that migrate to the thymus to eventually give rise to new T-cells., called lymphoid progenitors.
“Our goal was to enhance the production of these cells, which are like the entry product to the foundry that produces T-cells, by creating a little bone marrow-like environment”, said Scadden.
This novel development was based on the groundbreaking research of David Mooney Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences, and co-senior author on the paper. It involves biomaterials that provide cell-instructive cues allowing the creation of a sponge-like cell factory, with large pores that permit cells to move in and out. The material contains two built-in proteins, one that recruits outside cells, encouraging them to become bone cells, and the other to create the T-cell progenitors.
“We also found that not only are we enhancing the rate at which these T cells form after transplant but we are also increasing the diversity in the types of T cells that are formed”, said Nisarg Shah, lead author on the paper and currently a faculty member at the University of California. “So, we are improving not only the number of T-cells but also, potentially, the breadth of pathogen recognition capabilities and protection”.
These types of advancements in the field of biomedical engineering are the ones pushing forwards the fight against serious conditions and disease, like cancer, and will bring a new level of patient care and quality of life.
HOPE RISES With Us!