Trehalose Buffered Stem Cell Preservation Solution
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Solution Overview
Problem
Current solutions for preserving mesenchymal stem cells (MSCs) for therapeutic use have limitations in maintaining viability during storage and transport, with existing solutions often containing non-pharmaceutically approved components and providing inadequate long-term preservation, especially when intended for direct human administration.
Innovation Solution
A buffered water solution of trehalose with specific ion concentrations (K+, Na+, Cl-, PO4^3-, and Mg2+) is developed, maintaining a pH range of 7.1 to 7.6 and osmolarity up to 400 mOsm/l, which extends the viability of MSCs for at least 72 hours at 4 °C, making it suitable for storage and direct application.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of stationary object
If conventional organ transport solutions are used for stem cell preservation, then the cells can be stored for extended periods, but the solutions contain non-pharmaceutically approved components that cannot be directly administered to patients
Solution Approach 1:
The patent modifies the chemical composition parameters of the preservation solution by replacing non-pharmaceutical components with pharmaceutically approved substances. The solution contains specific concentrations of K+ (3-10 mmol/l), Na+ (130-150 mmol/l), Cl- (100-120 mmol/l), PO4^3- (1-5 mmol/l), and Mg2+ (0.5-2 mmol/l), along with trehalose (5-50 mmol/l) and buffering agents, creating a formulation that is both safe for human administration and effective for extended cell storage
Solution Approach 2:
The patent introduces trehalose as a key intermediary substance that serves multiple functions: it acts as a protective agent against cellular stress during storage, provides osmotic balance, and can be directly administered to patients. The trehalose concentration (5-50 mmol/l) is optimized to maintain cell viability while ensuring pharmaceutical safety for human use
2Loss of time
If stem cells are stored for extended periods to allow for proper characterization and testing, then safety and identity can be confirmed, but cell viability decreases over time
Solution Approach 1:
The patent performs preliminary protective actions by pre-formulating the preservation solution with optimal concentrations of protective agents including trehalose (5-50 mmol/l), buffering agents (KH2PO4 and Na2HPO4 at 1-10 mmol/l each), and electrolytes. This pre-prepared solution immediately provides protective effects when cells are introduced, preventing viability loss during the necessary characterization and testing period
Solution Approach 2:
The patent optimizes solution parameters including pH (7.0-7.6), osmolarity (250-400 mOsm/l), and ion concentrations to create an environment that maintains cell viability during extended storage. The specific combination of electrolytes and buffering agents keeps the solution within optimal physiological ranges, preventing cellular degradation over time
3Reliability
If complex multi-component preservation solutions are used, then cell protection is enhanced, but the solutions require multiple approvals for human administration and increase device complexity
Solution Approach 1:
The patent creates a universal preservation solution that simultaneously provides multiple functions: cell protection during storage, maintenance of physiological conditions, and suitability for direct human administration. The single formulation contains trehalose (5-50 mmol/l), buffering agents (KH2PO4 and Na2HPO4 at 1-10 mmol/l each), electrolytes (K+, Na+, Cl-, PO4^3-, Mg2+), and antioxidants, eliminating the need for separate protective agents and simplifying the overall system
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The solution effectively maintains high viability and functionality of MSCs for up to 72 hours, allowing for extended shelf life and safe transport, while being composed of pharmaceutically acceptable compounds suitable for direct intravenous or subcutaneous administration.
Implementation Method 1
Trehalose prevents the denaturation and inactivation of proteins, and protects the lipid bi-layer of cell membranes against damage
Implementation Method 2
Trehalose prevents the denaturation and inactivation of proteins, and protects the lipid bi-layer of cell membranes against damage
Implementation Method 3
Trehalose also likely serves as a source of carbon and glucose to provide cell functions
Implementation Method 4
as an absorber of free radicals, it provides protection against oxidative stress
Implementation Method 5
The solution contains, as necessary components, cations K+, Na+, Mg2+, anions Cl-, PO43- and buffering agents, which maintain the right pH
Implementation Method 6
provide the optimal osmolarity of the solution
Implementation Method 7
protect the cells against intracellular oedema, shrinkage, free radicals, apoptosis and other negative effects of hypothermia
Implementation Method 8
protect the cells against intracellular oedema, shrinkage, free radicals, apoptosis and other negative effects of hypothermia
Data Source
Figure 1A~1C
AI summary
A solution for the preservation, transport and application of stem cells for medical utilisation, that consists ofa buffer water solution of trehalose. The solution contains cations K+ in a quantity of 20 to 50 mmol/1, cations Na+ in a quantity of 20 to 80 mmol/1; anions CI" in a quantity of 0.5 to 40 mmol/1, anions PO43" and/or HPO42" and/or H2PO4" in a total quantity of 20 to 65 mmol/1, and trehalose in a quantity of 60 to 300 mmol/1 as necessary components. The concentration of the components has been selected in such a way that the pH of the solution is 7.1 to 7.6. The solution is intended for storing the cells at a temperature of - 4 °C to 25 °C, advantageously 0 °C to 8 °C, and most frequently 4 °C to 6 °C. Adequate viability of the cells is kept for a period of at least 72 hours.. The solution consists of pharmaceutically acceptable compounds, and it can be used for application of the stem cells that are kept directly within. The solution containing the stem cells is intended for the treatment of inflammatory diseases including post-traumatic inflammatory reactions after damage or injury, as well as for treatment of degenerative and neurodegenerative diseases. The solution containing the stem cells can also be used for the treatment of trauma, of developmental defects, for healing of wounds and skin burns, for tissue replacement, for treatment of locomotion system diseases (tendons, joints, inflammatory diseases, arthritis, and osteoarthritis), bone defects, diabetes, attacks, and cardiological and oncological diseases.