Review

. 2022 Jan 11;17(1):1-13.

doi: 10.1016/j.stemcr.2021.12.001. Epub 2021 Dec 30.

Biomanufacturing in low Earth orbit for regenerative medicine

Arun Sharma¹, Rachel A Clemens², Orquidea Garcia³, D Lansing Taylor⁴, Nicole L Wagner⁵, Kelly A Shepard⁶, Anjali Gupta², Siobhan Malany⁷, Alan J Grodzinsky⁸, Mary Kearns-Jonker⁹, Devin B Mair¹⁰, Deok-Ho Kim¹¹, Michael S Roberts¹², Jeanne F Loring¹³, Jianying Hu¹⁴, Lara E Warren¹², Sven Eenmaa¹², Joe Bozada¹⁵, Eric Paljug¹⁵, Mark Roth¹⁶, Donald P Taylor¹⁷, Gary Rodrigue¹², Patrick Cantini¹⁸, Amelia W Smith¹², Marc A Giulianotti¹⁹, William R Wagner²⁰

Affiliations

¹ Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Electronic address: arun.sharma@cshs.org.
² Axiom Space, Inc., Houston, TX, USA.
³ Johnson & Johnson 3D Printing Innovation & Customer Solutions, Johnson & Johnson Services, Inc., Irvine, CA, USA.
⁴ University of Pittsburgh Drug Discovery Institute and Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA, USA.
⁵ LambdaVision Inc., Farmington, CT, USA.
⁶ California Institute for Regenerative Medicine, Oakland, CA, USA.
⁷ Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, FL, USA.
⁸ Departments of Biological Engineering, Mechanical Engineering and Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁹ Department of Pathology and Human Anatomy, Loma Linda University School of Medicine, Loma Linda, CA, USA.
¹⁰ Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹¹ Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹² Center for the Advancement of Science in Space, Inc, Melbourne, FL, USA.
¹³ Scripps Research Institute, San Diego, CA, USA.
¹⁴ Center for Computational Health IBM Research, Yorktown Heights, New York, NY, USA.
¹⁵ Joseph M. Katz Graduate School of Business, University of Pittsburgh, Pittsburgh, PA, USA.
¹⁶ Pittsburgh, PA, USA.
¹⁷ The Ohio State University, Columbus, OH, USA.
¹⁸ McGowan Institute for Regenerative Medicine, Pittsburgh, PA, USA.
¹⁹ Center for the Advancement of Science in Space, Inc, Melbourne, FL, USA. Electronic address: mgiulianotti@issnationallab.org.
²⁰ McGowan Institute for Regenerative Medicine, Pittsburgh, PA, USA; Departments of Surgery, Bioengineering, Chemical Engineering, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: wagnerwr@upmc.edu.

PMID: 34971562
PMCID: PMC8758939
DOI: 10.1016/j.stemcr.2021.12.001

Review

Biomanufacturing in low Earth orbit for regenerative medicine

Arun Sharma et al. Stem Cell Reports. 2022.

. 2022 Jan 11;17(1):1-13.

doi: 10.1016/j.stemcr.2021.12.001. Epub 2021 Dec 30.

Authors

Affiliations

¹ Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Electronic address: arun.sharma@cshs.org.
² Axiom Space, Inc., Houston, TX, USA.
³ Johnson & Johnson 3D Printing Innovation & Customer Solutions, Johnson & Johnson Services, Inc., Irvine, CA, USA.
⁴ University of Pittsburgh Drug Discovery Institute and Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA, USA.
⁵ LambdaVision Inc., Farmington, CT, USA.
⁶ California Institute for Regenerative Medicine, Oakland, CA, USA.
⁷ Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, FL, USA.
⁸ Departments of Biological Engineering, Mechanical Engineering and Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁹ Department of Pathology and Human Anatomy, Loma Linda University School of Medicine, Loma Linda, CA, USA.
¹⁰ Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹¹ Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹² Center for the Advancement of Science in Space, Inc, Melbourne, FL, USA.
¹³ Scripps Research Institute, San Diego, CA, USA.
¹⁴ Center for Computational Health IBM Research, Yorktown Heights, New York, NY, USA.
¹⁵ Joseph M. Katz Graduate School of Business, University of Pittsburgh, Pittsburgh, PA, USA.
¹⁶ Pittsburgh, PA, USA.
¹⁷ The Ohio State University, Columbus, OH, USA.
¹⁸ McGowan Institute for Regenerative Medicine, Pittsburgh, PA, USA.
¹⁹ Center for the Advancement of Science in Space, Inc, Melbourne, FL, USA. Electronic address: mgiulianotti@issnationallab.org.
²⁰ McGowan Institute for Regenerative Medicine, Pittsburgh, PA, USA; Departments of Surgery, Bioengineering, Chemical Engineering, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: wagnerwr@upmc.edu.

PMID: 34971562
PMCID: PMC8758939
DOI: 10.1016/j.stemcr.2021.12.001

Abstract

Research in low Earth orbit (LEO) has become more accessible. The 2020 Biomanufacturing in Space Symposium reviewed space-based regenerative medicine research and discussed leveraging LEO to advance biomanufacturing for regenerative medicine applications. The symposium identified areas where financial investments could stimulate advancements overcoming technical barriers. Opportunities in disease modeling, stem-cell-derived products, and biofabrication were highlighted. The symposium will initiate a roadmap to a sustainable market for regenerative medicine biomanufacturing in space. This perspective summarizes the 2020 Biomanufacturing in Space Symposium, highlights key biomanufacturing opportunities in LEO, and lays the framework for a roadmap to regenerative medicine biomanufacturing in space.

Keywords: biofabrication; microgravity; microphysiological systems; organoids; stem cells.

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Figures

**Figure 1**
Examples of stem cell research aboard the ISS Top left: NASA astronaut Kate Rubins examines stem-cell-derived cardiomyocytes onboard the ISS. Top right: NASA astronaut Jessica Meir onboard the ISS working with engineered heart tissues. Bottom left: NASA astronaut Kate Rubins evaluates three-dimensional engineered heart tissue exposed to sustained microgravity conditions. Bottom Right: NASA astronaut Christina Koch examines a tissue chip system to study kidney function. Credit: NASA.

**Figure 2**
Breakdown of symposium participants’ expertise and primary role For those that identified stem cells as their primary expertise, 16 individuals’ primary role was academic (A), 5 were commercial (C), 5 were CASIS/Implementation Partners (CI), and 6 were government (G). Organoids/MPS had 12 A, 9 C, 5 CI, and 6 G. Biofabrication had 5 A, 17 C, 9 CI, and 6 G. AI/Robotics had 12 A, 17 C, 4 CI, and 4 G.

**Figure 3**
Examples of tissue engineering work aboard the ISS Left: engineered skeletal muscle tissue in a microfluidic chip in LEO, generated by Siobhan Malany Laboratory at the University of Florida in collaboration with Space Tango (credit: Siobhan Malany and Space Tango). Right: a NASA astronaut (out of frame) adds RNAlater reagent to a gas-permeable tissue chamber to preserve engineered heart tissue constructs for the Cardinal Heart investigation. Project led by Dr. Joseph Wu at Stanford University in collaboration with BioServe Space Technologies (credit: Joseph Wu and NASA).

**Figure 4**
Evolution of therapeutic discovery, testing, and translation pathways Development pathways integrated with automation, machine learning, and artificial intelligence can accelerate the process and utilize fewer resources

**Figure 5**
Biomanufacturing in low Earth orbit market subsegmentation revenue projection The LEO biomanufacturing market is broken into five primary subsegments: (1) cell and tissue tools and diagnostics, (2) cell and tissue therapy, (3) bioprinting, (4) cell therapy biomanufacturing, and (5) organoids. Projections are for the next 15 years.

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Biomanufacturing in low Earth orbit for regenerative medicine

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Biomanufacturing in low Earth orbit for regenerative medicine

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