The researchers at the Stowers Institute for Medical Research have come up with new research that claims to identify a backup for the hematopoietic system in the body. The study appeared online on January 15, 2019. It is published in the journal Cell Reports.
The hematopoietic system is comprised of stem cells that mature and differentiate into blood cells. Note that the adult stem cells constantly replenish the body’s cellular blood components.
The findings of the study provide evidence that hematopoietic stem cells (HSCs) consist of different functional populations of cells. One of these cell populations includes “primed” cells. These are activated when the first-line stem cells are damaged. They mature and differentiate to produce,
- Red blood cells
- White blood cells
- Reserve cells
Factors including radiation or chemotherapy pose severe stress on the body that injures the blood cells, including primed hematopoietic stem cells. This is when the reserve cells kick in.
Reserve stem cells hold the key to understanding the repopulation of blood cells after severe injury. Regenerative HSCs reside in the core of most bones. They churn out two million new blood cells every second. Only a fraction of these cells actively move through the cell cycle. However, the rest of the cells stay inactive, quiescent or dormant in the state. Several studies indicate that the majority of these quiescent stem cells are sensitive to DNA damage caused by chemotherapy.
Over a decade ago, the researchers suggested that a special population of HSCs, resistant to the damage, resides the bone marrow, in some hidden and unexplored niche. During this study, the researchers undertook a series of experiments to prove this concept.
What does the study say?
Mouse models were employed as test subjects for the experiments of the study. A key experiment made use of a cell surface marker to segregate reserve and primed HSCs. The mouse models were transplanted with these reserve HSCs or primed HSCs. After the establishment of the engraftments, the recipient mice were treated with the chemotherapy agent 5-fluorouracil (5-FU).
The blood cells derived from the primed HSCs reflected that they began to decline after the treatment. However, the reserve HSCs’ derivatives stayed intact and unscathed. In effect, the research showed that hematopoietic stem cells have functionally distinct subpopulations,
- One that acts under normal conditions
- The other that acts under times of stress
Furthermore, the researchers examined bone and marrow from transplanted mice. They labeled the reserve cells with fluorescent tags and studied them microscopically to locate them in the bone marrow.
What were the results?
It was found that the fluorescently labeled cells lurk in a specialized niche along the inside surface of the bone, adjacent to a population of cells known as N-cadherin+ bone-lining cells. It was the first niche identified to support HSCs back in 2003.
The research team of the study found that these N-cadherin+ bone-lining cells are mesenchymal or skeletal stem cells. They are potent enough to produce bone, cartilage, and fat. Therefore, N-cadherin may be used as a marker to isolate skeletal stem cells. Moreover, it may be helpful in bone and cartilage regenerative medicine.
These N-cadherin+ bone-lining cells protected the reserve cells from injury by feeding them with the survival factors. Upon depletion of these support cells, the reserve cells were no longer able to survive the chemotherapy treatment.
In addition, N-cadherin+ cells lining the bone were also resistant to chemotherapy. On the other hand, stromal cells in the central marrow were found sensitive to chemotherapy. This clearly suggests that N-cadherin+ cells support the reserve stem cells.
The results of the study advanced the understanding of HSC biology. It may open new possibilities for treating blood diseases e.g. leukemia and autoimmune disorders.