A novel, biologically inspired strategy will be used to improve preservation of mesenchymal stem cells (MSCs). MSCs are being investigated for the treatment of cardiovascular disorders, diabetes, connective tissue disorders, acute lung injury, amyotrophic lateral sclerosis, kidney diseases and more. The proposed investigation addresses a critical obstacle for widespread use of MSCs: a high quality, consistent preservation protocol. We believe that multicomponent solutions can preserve MSCs effectively. Testing that hypothesis using conventional methods could require up to ~7,000 experiments, which is clearly not practical. We have developed a computational algorithm that accelerates optimization and reduces the experimentation required. We propose to develop in Aim #1, several candidate preservation solutions using naturally- occurirng molecules that are biocompatible. Preliminary studies demonstrate that there is a `sweet spot' where the molecules of interest act in concert to improve the survival of cells. Outside of that range, the relationship amongst the molecules can actually be detrimental. The proposed investigation uses a variety of spectroscopic techniques to characterizing the potential molecular mechanisms for the protection afforded by the multi-component solutions in Aim #2. Finally, induced pluripotent stem (iPS) cells are another biological system of tremendous interest. We propose to apply the approach developed for MSCs to iPS colonies of cells and improve preservation of this important cell type in Aim #3. The proposed investigation has the potential to transform cell preservation by moving away from DMSO to biocompatible, naturally occurring molecules. Streamline processing protocols by eliminating introduction and washing steps. Enable development of fit-for-purpose preservation protocols that can vary with cell type and even application to application through the use of algorithm-driven protocol optimization.

Public Health Relevance

The long-term objective of this investigation is to develop effective methods of cells used therapeutically using naturally occurring molecules. The methods developed will improve function of the cells, reduce adverse reactions for patients receiving cells and improve access of patients to cells that can be used therapeutically.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB023880-03
Application #
9694661
Study Section
Biomaterials and Biointerfaces Study Section (BMBI)
Program Officer
Rampulla, David
Project Start
2017-08-03
Project End
2021-04-30
Budget Start
2019-05-01
Budget End
2021-04-30
Support Year
3
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Engineering (All Types)
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Pi, Chia-Hsing; Yu, Guanglin; Petersen, Ashley et al. (2018) Characterizing the ""sweet spot"" for the preservation of a T-cell line using osmolytes. Sci Rep 8:16223
Yu, Guanglin; Yap, Yan Rou; Pollock, Kathryn et al. (2017) Characterizing Intracellular Ice Formation of Lymphoblasts Using Low-Temperature Raman Spectroscopy. Biophys J 112:2653-2663