The secret to producing large batches of stem cells more efficiently may lie in the near-zero gravity conditions of space.

Microgravity is the proper term for “weightlessness” – very weak gravity, such as in a spacecraft orbiting the Earth. The final frontier is often seen as a keeper of secrets, but now scientists at Cedars-Sinai have discovered that microgravity could contribute to life-saving advances back down on the planet by facilitating the rapid mass production of stem cells.

A new paper, led by Cedars-Sinai and published in the peer-reviewed journal Stem Cell Reports, highlights key opportunities discussed during the 2020 Biomanufacturing in Space Symposium to expand the manufacture of stem cells in space. The symposium was meant to serve as the first step in developing a roadmap to establish a robust and sustainable market for biomanufacturing in space [1].

Longevity.Technology: Biomanufacturing is a type of stem cell production that uses biological materials such as microbes to produce substances and biomaterials suitable for use in preclinical, clinical and therapeutic applications and apparently this process can be more productive in microgravity which has novel conditions and control exerted on the directionality and geometry of cell and tissue growth can be markedly different from those on Earth. The Biomanufacturing in Space Symposium highlighted over 50 potential space-based commercial biomanufacturing opportunities, with the top three most promising categories being stem-cell-derived products, disease modelling and biofabrication.

“We are finding that spaceflight and microgravity is a desirable place for biomanufacturing because it confers a number of very special properties to biological tissues and biological processes that can help mass produce cells or other products in a way that you wouldn’t be able to do on Earth,” said stem cell biologist Arun Sharma, PhD, research scientist and head of a new research laboratory in the Cedars-Sinai Board of Governors Regenerative Medicine Institute, Smidt Heart Institute and Department of Biomedical Sciences.

“The last two decades have seen remarkable advances in regenerative medicine and exponential advancement in space technologies enabling new opportunities to access and commercialize space,” he said [2].

3D bioprinting is already established on the International Space Station, and the paper authors note that: “Utilizing microgravity has contributed to the collective fundamental knowledge of cellular behavior, cell-cell interactions, tissue development and regeneration, and aggregate interactions in the context of a whole organism. Pioneering bioengineering experiments on the ISS coupled with ground-based studies have demonstrated that microgravity enables the study of novel features not attainable under normal gravity conditions, including changes to stem cell proliferation rates and differentiation [3].”

Disease modelling

This process is used by scientists to study diseases and possible treatments by replicating full-function structures, using stem cells, organoids (miniature 3D structures grown from human stem cells that resemble human tissue), or other tissues.

Investigators have found that once the body is exposed to low-gravity conditions for extended periods of time, it experiences accelerated bone loss and aging. By developing disease models based on this accelerated aging process, research scientists can better understand the mechanisms of the aging process and disease progression.

“Not only can this work help astronauts, but it can also lead to us manufacturing bone constructs or skeletal muscle constructs that could be applied to diseases like osteoporosis and other forms of accelerated bone aging and muscle wasting that people experience on Earth,” said Sharma, who is the corresponding author of the paper.

Biofabrication

A hot topic at the symposium, biofabrication uses manufacturing processes to produce materials like tissues and organs. 3D printing is one of the core biofabrication technologies.

A major issue with producing these materials on Earth involves gravity-induced density, which makes it hard for cells to expand and grow. With the absence of gravity and density in space, scientists are hopeful that they can use 3D printing to print unique shapes and products, like organoids or cardiac tissues, in a way that can’t be replicated on Earth.

Stem cells

Scientists are interested in the production of stem cells and understanding how some of their fundamental properties are influenced by microgravity. Some of these properties include potency, the ability of a stem cell to renew itself, and differentiation, the ability of stem cells to turn into other cell types.

This unique ability to turn into any kind of cell means stem cells hold enormous therapeutic promise. Imagine being able to replace heart cells lost to heart disease, neurons lost to neurodegenerative disease or rebuilding a diseased kidney.

Understanding some of the effects of spaceflight on stem cells can potentially lead to better ways to manufacture large numbers of cells in the absence of gravity. Scientists from Cedars-Sinai plan to send stem cells into space later this year, in conjunction with NASA and a private contractor, Space Tango, to test whether it is possible to produce large batches in a low gravity environment.

“While we are still in the exploratory phase of some of this research, this is no longer in the realm of science fiction,” said Sharma. “Within the next five years we may see a scenario where we find cells or tissues that can be made in a way that is simply not possible here on Earth. And I think that’s extremely exciting.”

[1] https://www.issnationallab.org/iss360/future-space-biomanufacturing-unique-opportunity-symposium-preprints/
[2] https://www.cedars-sinai.org/newsroom/leveraging-space-to-advance-stem-cell-science-and-medicine/
[3] https://www.cell.com/stem-cell-reports/fulltext/S2213-6711(21)00598-1
Image credits: NASA & Cedars-Senai