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August 16, 2023
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Researchers aim to validate hematopoietic stem cell production in space

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A pathfinder spaceflight investigation has flown to the International Space Station with a goal of expanding a population of hematopoietic stem cells that retain their multipotency.

Stem cells grown on Earth lose their multipotency — the ability to become many different types of blood cells. Multipotency maximizes these cells’ ability to restore blood and immune function among patients with cancer.

Quote from Louis Stodieck, PhD

“Hematopoietic stem cells grown in culture do best in an environment where they are suspended, meaning they don’t attach to a surface like many cells do. You have to keep them suspended because otherwise, they settle to the bottom and get crowded,” principal investigator Louis Stodieck, PhD, research professor and chief scientist with BioServe Space Technologies at University of Colorado Boulder, told Healio. “We want to maintain them in a suspended but quiescent state. We want to inhibit their differentiation and maintain them in a condition that would allow them to establish a large population of cells that can provide long-term potency in patients and support their immune systems for many years.”

Stodieck spoke with Healio about the origin of this experiment, the methodology and what he hopes to learn from this project.

Healio: What inspired this study?

Stodieck: There is a lot of interest in hematopoietic stem cells, especially in terms of expanding stem cells and maintaining their multipotency. When you start looking at transplantation applications with leukemias and lymphomas, maintaining multipotency can shorten hospital stays and improve patient outcomes, time to engraftment and survival. We wanted to go into space — to access a weightless environment — to be able to grow these cells in a quiescent, very low-shear environment where they’re not being moved and suspended by rockers, shakers, stirring impellers or whatever techniques are used on Earth.

The idea is to create an environment where these cells can expand. Obviously, we need to have the right media, the right growth factors and the right sort of molecules in there that will potentially inhibit their differentiation.

Healio: How will you evaluate the expansion of the cells in space?

Stodieck: We obtain human cord blood cells and media and develop specialized bioreactors and support kits that can be used in a space flight environment. We then launch all of these items for transport up to the International Space Station.

The cells are cryopreserved and launched in a frozen state. The crew on the space station unloads the various supplies that are sent up, including our experiment. They have freezers onboard the transport vehicle and the space station. They will take the cells, which in this case are umbilical cord CD34-positive cells. CD34 is one way to characterize the specific stems cells that we want, as opposed to differentiated erythrocytes or immune system cells.

Once the cells are in orbit, and once the crew is ready, we will have them seed the cells into our spaceflight bioreactors. They will go through steps to remove the cryo-preservative, resuspend the cells into our growth media and inject them into our bioreactors. We will allow them to grow for 10 days. This particular experiment is an initial flight test for us. We expect an increase in the cell population, probably more than 200-fold, within that timeframe. We will separately grow cultures on Earth using cells from the same donors used in the flight experiment.

We will take samples as we go. We will cryopreserve those samples, bring them back and analyze them to see how well the cells maintain their multipotency. There are biomarkers for hematopoietic stem cells that can help distinguish the various cell types expected in the population. We will use those markers to characterize the cells when they expand in space and compare them to the controls we grow on Earth.

Healio: What is the study timeline?

Stodieck: The experiment launched on an unmanned Northrop Grumman cargo mission on Aug. 1. It docked with the space station on Aug. 4. The first part of the experiment — thawing and seeding the cells into the bioreactors — was completed on Aug. 8 by astronaut Frank Rubio, MD, with the assistance of astronaut Sultan Al Neyadi, PhD. Once we’ve expanded the cells and obtained the samples and harvested the cells, they’ll be brought back to Earth on a crew return mission at the end of August. Then we’ll be able to analyze them in detail.

Healio: What are the next steps?

Stodieck: If the experiment is successful, we will conduct future studies to refine spaceflight stem cell production. We hope eventually to be able to produce clinical-grade cell therapies to treat patients here on Earth.

Reference:

For more information:

Louis Stodieck, PhD, can be reached at Ann and H. J. Smead Aerospace Engineering Sciences, 429 UCB, 3775 Discovery Drive, Boulder, CO 80303; email: louis.stodieck@colorado.edu.