Cell therapy products is >$1 billion market with aggressive annual growth rates (15- 20%). Of all of the cells therapies currently in development, mesenchymal stem cells (MSCs) appear to have the greatest diversity of applications and potential for widespread use. Mesenchymal stem/stromal cells (MSCs) are being investigated for a variety of applications. Currently, over 200 clinical trials involve the use of MSCs and over 2000 patients have been safely treated with MSCs. MSCs are being investigated for treatment of cardiovascular disorders (stroke, myocardial infarction), diabetes, connective tissue disorders (cartilage defects, osteonecrosis, limb ischemia), chronic obstructive pulmonary disease, nervous system disorders (multiple sclerosis, Parkinson Disease, spinal cord injury), kidney diseases and more. Current methods for the preservation of MSCs are suboptimal. Improper methods of preservation are felt to have contributed to a recent failure of a Phase III clinical tral. In addition, the infusion of DMSO-containing cells is associated with adverse events that have been well documented in the clinical literature. Clinical and commercial application of MSCs will require the development of protocols that produce a consistent number of viable and functional cells. The proposed investigation transforms not only the preservation protocol for MSCs but creates a new paradigm by which preservation protocols for other cell types can be developed. We propose to use synergy between multiple preservation compounds to improve preservation outcome and replace conventional toxic cryoprotective agents such as DMSO. Testing solutions using multiple compounds would normally require thousands of experiments. We accelerate the convergence of the studies using a computational algorithm. Finally, we will use molecular dynamics to understand molecular mechanisms of action and rationally select compounds appropriate for testing. This type of approach will be applied first of all to MSCs but can be extended to a variety of different cell types used therapeutically. !

Public Health Relevance

Mesenchymal stem cells are being used to treat a variety of diseases but clinical use of the cells has been limited by the quality of cells post thaw. We are proposing to develop an optimal protocol for the preservation of MSCs using stabilizing agents safe not only for the cells and patients receiving the cells. A more effective protocol for preserving MSCs will enable the treatment of more diseases using these cells and more people being able to receive cell-based therapies.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Exploratory/Developmental Grants (R21)
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Instrumentation and Systems Development Study Section (ISD)
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Hunziker, Rosemarie
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University of Minnesota Twin Cities
Engineering (All Types)
Schools of Engineering
United States
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