Blood is vital for our survival. With approximately 10 pints running through our veins, our blood has three main functions; to transport compounds such as gases and nutrients, to protect against pathogenic invasion and to regulate physiological properties, such as the bodies pH and water balance.
Remarkably, our body produces approximately 2 million red blood cells every second from specialised stem cells found in our bone marrow in a process called haematopoiesis. However, previous studies have suggested that only a tiny portion of these cells are active at any given time; the rest of the haematopoietic stem cells (HSCs) lie in an inactive state.
A group of researchers at the Stowers Institute for Medical Research, led by Professor Linheng Li, have studied the complex haematopoietic system for many years and very clearly described their take on how it all works, “One population is very active, to support blood production, but there’s another small population that’s normally not active because it’s in a sleeping state,” says Li. “When you have stresses, such as blood loss, this population can wake up and become active. You hear a lot of talk these days about the strategic oil reserve. Well, this is the same idea: a strategic stem cells reserve.”
However, cancer treatments such as radio- and chemotherapy depletes blood cells counts and in some cases, cancer treatments have to be temporarily halted to allow the body to replenish its essential stocks. It was previously believed that the HSCs maintaining an inactive state within the bone marrow protected them from DNA and cellular damage, however, more recently, it has been found that these HSCs are in fact particularly susceptible to DNA damage from chemotherapy and disease.
Professor Li and his collaborators have focused their recent research efforts on the key question; how exactly do HSCs manage to repopulate blood cells after they’ve been damaged and depleted by chemotherapy?
“Over a decade ago, Li suggested that a special population of HSCs that are resistant to damage might still reside in the bone marrow, hidden in some unexplored niche.”
Published in Cell Reports on the 15th January 2019, Li et al., suggest that reserve HSCs can be divided into functionally distinct subsets. Interestingly, they describe one of the reserve HSC subsets to be resistant to chemotherapy. Localised in a specialised niche of the inner bone surface region of the bone marrow, these HSCs are fed protective molecules and factors by their surrounding cells enabling them to survive chemotherapy-induced DNA damage. When these support cells were experimentally depleted, the resistant, reserve HSCs could no longer survive chemotherapy treatment.
Understanding how exactly these HSCs endure chemotherapy to survive could have huge implications for the treatment of blood diseases, such as leukaemia. Previous research has shown that, like HSC populations, there are distinct active and inactive, or reserve, tumour cell populations. Initial treatments target the active populations, however, often the inactive, reserve tumour cells “wake up” and multiply and this has been suggested to explain the reason behind cancer relapses.
If these inactive cells reside in a specialised niche and are able to withstand chemotherapy like the resistant HSCs, then perhaps by identifying and removing their supporting or protective cells, researchers may be able to target both active and sleeping tumour cells to treat cancers effectively.
This post was written by Ella Mercer (She/her) and edited by Karolina Zieba (She/her).