A microfluidic device that emulates the heartbeat and blood circulation of an embryo. Cell-seeded channels are indicated with red food dyes, ventricular contraction control channels and circulating valve control channels in the heart are indicated with blue and green food dyes, respectively.Credit: Jingjing Li, UNSW Sydney
New discoveries in the creation of embryonic blood stem cells, made independently by biomedical engineers and medical researchers at the University of New South Wales (UNSW) Sydney, may one day eliminate the need for blood stem cell donors.
These achievements are part of a movement in regenerative medicine towards the use of ‘induced pluripotent stem cells’ to treat disease. This is where stem cells are reverse engineered from adult tissue cells rather than using live human or animal embryos.
I knew about Induced pluripotent stem cells since 2006researchers still have much to learn about how to artificially and safely mimic human cell differentiation in the laboratory for the purpose of providing targeted medicine.
Induced pluripotent stem cells are a type of pluripotent stem cells that can be generated directly from somatic cells. A somatic cell is any living cell that forms the body of a multicellular organism other than a gamete, germ cell, gametocyte, or undifferentiated stem cell.
UNSW researchers have recently completed two studies in this area, describing not only how blood stem cell precursors arise in animals and humans, but also how they can be artificially induced. Shining a new light.
One study was published in the journal on September 13, 2022. cell report By scientists from the UNSW School of Biomedical Engineering. They showed how simulation of a beating embryonic heart using a microfluidic device in the lab led to the development of human blood stem cell ‘progenitors’, stem cells on the verge of becoming blood stem cells.
In another recently published article, nature cell biologyresearchers at UNSW Medicine & Health have revealed the identity of cells in mouse embryos involved in creating blood stem cells.
Both studies are important steps in understanding when, where and which cells are involved in the creation of blood stem cells. In the future, this knowledge may be used to replenish depleted blood stem cells in cancer patients who have undergone high-dose radiation or chemotherapy.
emulate the mind
In a study detailed in cell reportlead author Jingjing Li, Ph.D., and fellow researchers, proposed that a 3 cm x 3 cm (1.2″ x 1.2″) microfluidic system could be used to mimic the beating heart and blood circulation conditions of an embryonic stem cell line. I explained how to send out the blood stem cells generated from.
For decades, she says, biomedical engineers have tried to make blood stem cells in laboratory dishes to solve the problem of blood stem cell shortages in donors. Is not …
“Part of the problem is that we still don’t fully understand all the processes going on in the developing microenvironment that lead to the creation of blood stem cells around day 32 of embryonic development,” Dr. Li said. said.
“So we created a device that mimics the heartbeat and blood circulation, and an orbital vibration system that induces shear stress or friction on the blood cells as they move within the device or dish.”
These systems facilitated the development of progenitor blood stem cells that can differentiate into various blood components such as leukocytes, erythrocytes and platelets. They were thrilled to see this same process, known as hematopoiesis, replicated in a device.
Study co-author Robert Nordon said the device not only generated blood stem cell precursors that generate differentiated blood cells, but also the tissue cells of the embryonic heart environment that are essential for this process. said he was surprised. .
“What amazes me about this is that when blood stem cells form in the embryo, they form in the walls of a major blood vessel called the aorta. enters and travels to the liver to form what is called final hematopoiesis or final hematopoiesis.
“Forming the aorta and actually releasing cells from that aorta into circulation are the critical steps necessary to generate these cells.”
“What we have shown is that we can generate cells that can form all the different types of blood cells. We know its origin is correct and we know it will propagate,” said A/Prof. Norton.
Researchers are cautiously optimistic about their success in emulating fetal heart conditions with a mechanical device. We hope that it will be a step towards solving the challenges that limit regenerative medicine today, such as the scarcity of donor blood stem cells, rejection of donor tissue cells, and ethical issues surrounding the use of IVF embryos.
“Blood stem cells used for transplantation require a donor of the same tissue type as the patient,” said A/Prof. Norton.
“Manufacturing blood stem cells from pluripotent stem cell lines solves this problem without the need for histomatched donors, which provide a bountiful supply to treat blood cancers and genetic diseases.”
Dr. Li added:
To solve a mystery
Meanwhile working independently from Dr. Lee and A/Prof. Nordon, Professor John Pimanda of UNSW Medicine & Health, and Dr. Vashe Chandrakanthan conducted original research into how blood stem cells are made in the embryo.
In the mouse study, researchers looked for a mechanism naturally used in mammals to make blood stem cells from the cells that line blood vessels known as endothelial cells.
“It was already known that this process takes place in mammalian embryos and that the endothelial cells lining the aorta transform into blood cells during hematopoiesis,” said Prof Pimanda.
“But the identity of the cells controlling this process has been a mystery until now.”
In their paper, Prof. Pimanda and Dr. Chandrakantan describe how they solved this puzzle by identifying cells within the embryo that can convert both embryonic and adult endothelial cells into blood cells. Did. Known as ‘Mesp1-derived PDGFRA+ stromal cells’, these cells lie beneath the aorta and only surround the aorta with very narrow fenestrae during embryogenesis.
Chandrakantan said that knowing the identity of these cells could give medical researchers clues about how adult mammalian endothelial cells come to produce blood stem cells. I was.
“Our study showed that when endothelial cells from embryos or adults were mixed with ‘Mesp1-derived PDGFRA+ stromal cells’, they began to produce blood stem cells.
Although more research is needed before translating this into clinical practice, including confirming results in human cells, this discovery could provide a potential new tool for generating transplantable hematopoietic cells. There is a nature.
“By using your own cells to generate blood stem cells, you can eliminate the need for donor transfusions or stem cell transplants. We can get closer,” said Professor Pimanda.
References:
“Mimicry of Embryonic Circulation Promotes Hoxa Hematopoietic Niche and Human Blood Development,” Jingjing Li, Osmond Lao, Freya F. Bruveris, Liyuan Wang, Kajal Chaudry, Ziqi Yang, Nona Farbehi, Elizabeth S. Ng, Edouard G. Stanley, Richard P. Harvey, Andrew G. Elephanty, Robert E. Nordon, 13 Sept. 2022, cell report.
DOI: 10.1016/j.celrep.2022.111339
“Mesoderm-derived PDGFRA+ Vashe Chandrakanthan, Prunella Rorimpandey, Fabio Zanini, Diego Chacon, Jake Olivier, Swapna Joshi, Young Chan Kang, Kathy Knezevic, Yizhou Huang, Qiao Qiao, Rema A. Oliver, Ashwin Unnikrishnan, Daniel R. Carter, Brendan Lee, Chris Brownlee, Carl Power, Robert Brink, Simon Mendez-Ferrer, Grigori Enikolopov, William Walsh, Berthold Göttgens, Samir Taoudi, Dominik Beck, John E. Pimanda, 28 July 2022, nature cell biology.
DOI: 10.1038/s41556-022-00955-3
Funding: National Health and Medical Research Council, Stem Cells Australia, Stafford Fox Medical Research Foundation, Novo Nordisk
