Establishing Production of Stem Cell Therapies

Cell therapy, especially on a large scale, will require a significant increase in high quality stem cell production. Through research launched aboard Ax-2 in May 2023, scientists took an important step towards seeing if space could be the tool to solve this issue.

The Cedars-Sinai Regenerative Medicine Institute partnered with Axiom Space to launch the Stellar Stem Cells in Space project which explored the production of induced pluripotent stem cells (iPSCs) from skin cells in low-Earth orbit. The mission marked the first time in which iPSCs were manufactured in space by astronauts.

iPSCs are important in medicine because they can produce a variety of tissue cells, including heart, brain, and blood tissues, which could be used in regenerative medicine on Earth. Maintaining pluripotency, the ability to transform into all those cell types, is crucial for cell therapy. However, Earth’s gravity can cause some challenges to keeping pluripotency during their production. It is difficult for the iPSCs to expand and grow under these conditions.

“When the stress of gravity is not there pulling on the cells, we want to test whether they grow faster, have fewer genetic changes and remain in the pluripotent state,” said Clive Svendsen, PhD, executive director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute and co-principal investigator on the mission. “Then, when we turn them into the critical cells we need for healthcare, we will see if they do it better in microgravity. That is the goal of this new mission, and we are all very excited to see what happens up there.”

For the study, the team sent stem cells and skin cells to the International Space Station for five days. Axiom astronauts Rayyanah Barnaw and Peggy Whitson conducted this study on behalf of the scientists in orbit. Analyzing the stem cells in orbit showed researchers how quickly the cells divide in microgravity. This paired with data on the process of reprogramming adult skin cells into stem cells in space could give a good picture of the potential for stem cell production in space.

“If we can grow cells two- or three-fold better than what we can do on the ground, that’s really exciting not just for basic science for using these stem cells but also for clinical applications,” said Stellar Stem Cells in Space co-principal investigator Arun Sharma, PhD.

The data was returned back to the researchers on Earth for analysis. More stem-cell-focused experiments are planned to follow to build on these initial results.

"It is exciting to see the wide range of important research that will be conducted on this mission and to be taking the first steps in developing future in-space manufacturing applications for some of our biomedical products," said Christian Maender, executive vice president of in-space solutions at Axiom Space.

This project is part of the NASA In-Space Production (InSPA) program.

Biomanufacturing Organ Replacements

Creating an organ that can be placed into the human body is an incredibly challenging scientific task. However, microgravity is able to make the process slightly less challenging.

On Earth, bioprinting must fight against the 3D printed material being bent out of shape by the forces of gravity. A structure or scaffold is needed to assist the tissue in forming the needed 3D shapes. In microgravity, no scaffold is needed. While we still have a way to go before printing an organ in space, scientists think it could be the perfect place to advance the future of tissue engineering.

Wake Forest Institute for Regenerative Medicine (WFIRM) partnered with Axiom Space and BioServe Space Technologies to pursue a groundbreaking initiative that could help build the blocks needed for printing human organs in space. Known as the Space Tissue and Regeneration (STAR) project, the experiment launched aboard the Ax-2 mission in May 2023, sending six kidney and six liver bioprinted tissue constructs to the International Space Station. Some samples were preserved at 5 days of microgravity exposure, while others were preserved at ten days before they were then returned to Earth.

Bioengineered liver and kidney constructs flying to space will help researchers understand microgravity’s effects on vascular used tissues. Image courtesy of Wake Forest Institute for Regenerative Medicine

“This experiment is the first time that we’ve actually sent solid bioprinted organ tissue into space,” said Anthony Atala, M.D. at the Wake Forest Institute for Regenerative Medicine. “It’s an important mission that will allow us to look at the early time points in the tissue’s development for viability.”

STAR is a continuation of the NASA Centennial Vascular Tissue Challenge, where WFIRM teams won first and second place for creating metabolically active thick liver tissue that retained function for thirty days. Blood vessels supply cells with nutrients and oxygen and remove metabolic waste from tissues. The teams won this challenge by developing and testing strategies for making tissues with functional artificial blood vessels. The ISS National Lab then worked with the winning team to adapt the winning Earth-based strategy for space.

The goal for this next step study was to examine how these tissues and cells responded to microgravity and what impact space has to the development of vascular networks in microgravity. Researchers took a close look at cell adhesion, which enables cells to stick together and form the needed 3D structures in organs. This is all critical information for bioengineering entire organs for transplantation.

All of this effort is worth it to assist the more than 100,000 people currently on the United States organ transplant wait list. Millions more do not qualify to even get on the list because of complicating factors such as age and lifestyle. By creating organs in space, it could help save the lives of the 17 people that currently die each day waiting for an organ.

The focus of this research on livers and kidneys is especially important for solving this issue, as these organs have the largest number of people currently waiting for them. As of January 2023, more than 88,000 people were waiting for a kidney and more than 10,000 waiting for a liver transplant in the US alone. However, once validated, this platform created by WFIRM teams for creating thick tissue could be used to produce even more tissue construct types.


Read more:

https://www.issnationallab.org/ax2-wake-forest-regen-med/

https://www.nasa.gov/mission/station/research-explorer/investigation/?#id=8921

https://school.wakehealth.edu/research/institutes-and-centers/wake-forest-institute-for-regenerative-medicine/awards-honors-and-media-coverage/2023/wfirm-bioprinting-research-makes-history-when-it-soars-to-the-iss

https://www.nasa.gov/news-release/teams-engineer-complex-human-tissues-win-top-prizes-in-nasa-challenge/