Editor’s note: Researchers discover that human and mouse stem cells cultured in the lab fiercely maintain the developmental rates found in nature. The discovery highlights a challenge in generating and maturing therapeutic cells from stem cells to quickly help patients.
Motivation behind the research
Stem cells are an exciting future therapy tool for regenerative medicine. “Pluripotent” stem cells are cells that can become essentially any cell type in the human body, such as neurons of the brain or spinal cord, blood cells, liver cells, kidney cells, skin cells, and so on.
Stem cells are undifferentiated cells that are capable of giving rise to indefinitely more cells of the same type, and also transform into any other cell type
These stem cells could therefore potentially serve as a limitless source of healthy replacement cells when any tissue or organ in the body breaks down due to injury or disease, including spinal cord injuries, Huntington’s, Alzheimer’s, or Parkinson’s diseases, organ failure, stroke, cancer, heart attack, etc. However, the time it takes to make these mature cells from stem cells can take months to years, and thus shortening the time it takes to make cells capable of helping patients poses a serious challenge to the clinical use of stem cells.
Interestingly, when embryonic stem cells from different species are cultured in the lab, they develop at different rates. However, how closely these rates mimic developmental rates found in real life remains a mystery. We set out to establish how closely these rates reflect natural developmental rates and to test how easily these rates could be altered.
In a side-by-side race, mouse and human stem cells were cultured to become neurons in the laboratory and rates of development were closely monitored. We found that mouse cells were indeed much quicker at developing into neurons than human cells, taking only days for mouse cells compared to several weeks for human cells.
When we compared the developmental rates of stem cells in the lab to those in nature, we were amazed at the incredible level of similarity. Rates of development found in mouse stem cells grown in the lab shockingly mirrored those found in nature, while the human stem cells similarly reflected normal rates of human development.
We further tested to see how fiercely cells maintain this innate developmental timer by monitoring rates of human stem cell development when grown inside a mouse. Rather than being sped up by the mouse environment, the human cells stubbornly retained their human rate of development. Altogether, these results point to the existence of an innate species-specific developmental clock.
This study only followed human and mouse stem cells, and therefore the maintenance of developmental timing for stem cells from other species remains to be confirmed.
Future work will focus on identifying how the developmental clock works, and moreover to test how the clock can be sped up to get clinically-relevant cell types to patients more quickly. While the retention of species-specific developmental timing by stem cells presents a practical challenge, it also represents an opportunity, as pluripotent stem cells offer a new tissue culture model to study the relationship between developmental timing and scale in mammals.
This latter realization is important because the extreme range of body sizes in mammals has fascinated developmental biologist for years. Mammals vary in size by an astounding 100 million fold, ranging from the 1.8g Etruscan shrew to the 181 metric ton blue whale. Furthermore, mammals also exhibit a broad range of pregnancy lengths, ranging from the opossum (~12 days) to that of the African elephant (~22 months). What is responsible for setting species-specific developmental timing is a biological mystery. Since species-specific developmental timing is maintained by stem cells, stem cells offer a new opportunity to study the control of developmental timing across the entire range of mammalian body sizes. For although it was previously impossible to perform experimental embryology in a blue whale, stem cells could effectively bring whale embryology into the laboratory.
Research Article: Species-Specific Developmental Timing Is Maintained by Stem Cells Ex Utero. Developmental Biology (2017). Apr 11;8(4):907-918
Scientist Bio: Chris Barry is an assistant scientist at the Morgridge Institute for Research in Madison, WI, USA. He was born and raised in Calgary, Canada, and is an avid hockey fan, outdoors and nature enthusiast, and Star Wars buff.
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