The secret to producing large batches of stem cells more efficiently may lie in the near-zero gravity conditions of space. Scientists at Cedars-Sinai report that microgravity has the potential to contribute to life-saving advances on Earth by facilitating the rapid mass production of stem cells.

A paper (“Biomanufacturing in low Earth orbit for regenerative medicine”), led by the Cedars Sinai team and published in Stem Cell Reports, highlights key opportunities discussed during the 2020 Biomanufacturing in Space Symposium, to expand the manufacture of stem cells in space. Attendees at the virtual space symposium in December identified more than 50 potential commercial opportunities for conducting biomanufacturing work in space, according to the Cedars-Sinai paper. The most promising fell into three categories: disease modeling, biofabrication, and stem-cell–derived products. The newly published Stem Cell Reports perspective concludes, “The symposium will initiate a roadmap to a sustainable market for regenerative medicine biomanufacturing in space.”

Over the last decade, the International Space Station National Laboratory (ISS National Lab) has supported space-based studies in the areas of tissue engineering and regenerative medicine, the authors noted. “This initial research and development have provided important insights into how microgravity can be leveraged to advance biomanufacturing in space to benefit human life and commercial enterprise on Earth.” Exploiting microgravity has given scientists new insights into fundamental aspects of cellular behavior, cell-cell interactions, tissue development, and regeneration, in the context of the whole organism, the team continued. Moreover, “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.”

The Biomanufacturing in Space Symposium was established to serve as the first step in developing a roadmap to a sustainable market for biomanufacturing in low Earth orbit (LEO) space. Biomanufacturing, which uses biological materials such as microbes to produce substances and biomaterials suitable for use in preclinical, clinical, and therapeutic applications, can be more productive in microgravity conditions, the authors noted. “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.”

Of the 50 potential commercial opportunities identified, the most promising fell into three areas; disease modeling, stem cells and stem-cell–derived products, and biofabrication. Disease modeling is an approach used by scientists to study diseases and possible therapeutic approaches, by replicating full-function structures—whether 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. “… the opportunity to uniquely isolate the stresses induced by sustained microgravity could provide significant insights into the aging process and disease progression,” the investigators wrote in their paper. “Data from associated space-based studies indicate that humans experience significant physiological changes during adaptation to spaceflight and during readaptation upon return to Earth.”

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.

Another highly discussed topic at the symposium was biofabrication, which 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.

“ … biofabrication discussions covered a wide variety of opportunities, including fabricating tissues for disease modeling, testing and maturation of biofabricated materials, and improved fabrication processes for biomaterials and biofabricated constructs, the review noted. “The collective need for novel approaches to produce implants, tissues, and organs is a public concern, and there are opportunities for government agencies to put resources into utilizing a unique environment such as a LEO-based platform to advance the field.”

The third category is centered on 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, effectively the ability for stem cells to turn into other cell types.

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. Stem cells and stem-cell-derived products have two primary customer bases, the authors noted. Firstly, those who utilize stem cells as research tools, and secondly, those who utilize stem cells in therapeutic applications. Symposium participants generally agreed that in the near term, the largest value return-on-investment will be derived from the data that can be translated to improve terrestrial processes, products, and tools, the authors noted. “However, the participants felt that, ultimately, the large-scale production of certain types of stem cells and stem-cell-derived products could benefit from manufacturing in a LEO-based facility and that the LEO environment could confer certain advantages that may not be replicated in a terrestrial setting.”

Scientists from Cedars-Sinai will be sending stem cells into space early next 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,” Sharma said. “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.”

As the authors of the perspective reported, “It is time to leverage LEO to conduct research and development that demonstrate the value of space-based biomanufacturing and its benefits to humankind. This will enable the investment required for a robust biomanufacturing market in space, and this symposium was a first step toward developing this future.”

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