# Multicomponent solutions for the preservation of cell therapy products

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2021 · $396,514

## Abstract

Project Abstract
A novel, biologically inspired strategy will be used to improve DMSO-free preservation of cardiomyocytes
derived from human induced pluripotent stem (hiPS) cells cultured as aggregates. Multicellular systems
respond poorly to conventional preservation methods. In the previous funding cycle, a differential evolution
algorithm was used to optimize the preservation of cells using combinations of sugars, sugar alcohols and
amino acids. This approach mimicked the strategies of plants and other simple organisms that survive
environmental stresses. Studies characterizing the behavior of multicomponent osmolyte solutions
demonstrated that osmolytes present in these solutions interact with each other to modify the behavior of water
during freezing which manifests itself at a molecular level (hydrogen bonding) as well as changes in
microstructure. The osmolytes also interact with critical biological structures in the cell to stabilize them. Low
temperature Raman spectroscopy studies demonstrated that multicellular systems are sensitive to
undercooling (the temperature difference between the freezing temperature and the temperature at which ice
forms in the extracellular solution). As we transition from single cells to aggregates, once again, we are looking
to nature for inspiration. The wood frog uses combinations of osmolytes, suppressed cell metabolism, and
minimizes undercooling as it adapts to freezing conditions in the winter. We are proposing a similar approach
to improving preservation of cardiomyocyte aggregates. The studies described in the application characterize
the freezing response of iPSC-derived cardiomyocytes at the committed cardiac progenitor stage and when
formed into fully differentiated, multicellular cardiac constructs. The influence of undercooling on post thaw
recovery of fully differentiated multicellular cardiac constructs will also be determined. The influence of
suppressing cell metabolism on post thaw recovery of multicellular constructs will also be quantified. On a
fundamental level, these studies will advance our understanding of the freezing behavior of more complex
multicellular systems. On an applied level, the proposed investigation has the potential to preservation of cells
differentiated from hiPS cells through the use of naturally inspired strategies.

## Key facts

- **NIH application ID:** 10200145
- **Project number:** 5R01HL154734-05
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** ALLISON HUBEL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $396,514
- **Award type:** 5
- **Project period:** 2017-08-03 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10200145

## Citation

> US National Institutes of Health, RePORTER application 10200145, Multicomponent solutions for the preservation of cell therapy products (5R01HL154734-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10200145. Licensed CC0.

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