Scientists at the University of New South Wales in Australia have developed a method to produce human blood stem cell precursors from human pluripotent stem cells. The method may have use in treating cancer patients who require high doses of such blood stem cells to help replenish endogenous populations that have been destroyed by chemotherapy.
The researchers exploited the tendency of cells to respond to mechanical stimuli and cultured the pluripotent stem cells in a microfluidic device that mimicked the pulsatile flow of the embryonic heartbeat. Given that human blood stem cells naturally form during embryonic development, the Australian team hypothesized that mimicking these conditions in vitro would help the cells to develop as blood stem cells.
Chemotherapy can have pretty devastating effects on blood cells and the stem cells that differentiate to produce them. There is a current shortage of donor stem cells to assist such patients, and researchers have struggled to create suitable stem cells in the lab.
Creating induced pluripotent stem cells from adult human cells has been an important step along the way in that it helps to avoid the need for embryonic cells or cells from animals. However, getting such cells to reliably turn into human blood stem cells that can then differentiate into any type of blood cell has been a challenge.
To address this, these researchers have turned to a microfluidic device to see if they could use mechanical stimuli to persuade induced pluripotent stem cells to turn into blood stem cells, or at least advance them somewhat down that path. The device mimics the pulsatile flow of the embryonic heartbeat, doubtless an important stimulus for cells within the developing embryo.
“Part of the problem is that we still don’t fully understand all the processes going on in the microenvironment during embryonic development that leads to the creation of blood stem cells at about day 32 in the embryonic development,” said Jingjing Li, one of the leaders of the project. “So we made a device mimicking the heart beating and the blood circulation and an orbital shaking system which causes shear stress — or friction — of the blood cells as they move through the device or around in a dish.”
So far, the researchers have shown that the device can stimulate the cells to develop into blood stem cell precursors. These cells can then go on to differentiate into any kind of blood cell. The team hopes to scale the technique up to work in a bioreactor, allowing them to produce large numbers of cells.
“Blood stem cells used in transplantation require donors with the same tissue-type as the patient,” said Robert Nordon, another researcher involved in the study. “Manufacture of blood stem cells from pluripotent stem cell lines would solve this problem without the need for tissue-matched donors providing a plentiful supply to treat blood cancers or genetic disease.”
Study in journal Cell Reports: Mimicry of embryonic circulation enhances the hoxa hemogenic niche and human blood development