Cell Preservation Composition Using Naringenin and Defined Buffers
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Solution Overview
Problem
Current compositions for the transportation and cryopreservation of cells, tissues, and organs, particularly those from non-invasive sources like hair follicles and urine-derived cells, face challenges such as sub-optimal viability due to temperature fluctuations, contamination risks from animal components, and toxicity from high DMSO concentrations, leading to compromised suitability for therapeutic use.
Innovation Solution
A composition comprising naringenin, a buffering system, and a sugar component, optimized for transportation and cryopreservation, which includes specific concentrations of naringenin (0.01 μM to 0.25 μM), a synthetic biological buffer, D-glucose, and reduced DMSO levels, along with antioxidants and antibiotics, to maintain viability and reduce contamination risks.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If prior art compositions (HypoThermosol, AQIX, Viaspan) are used for hypothermic storage, then osmotic balance and temperature stress protection are maintained, but cell viability deteriorates during extended transportation by mail or postal services
Solution Approach 1:
The patent modifies the chemical composition parameters of the storage medium by incorporating specific antioxidants (vitamin C, vitamin E, alpha-tocopherol), anti-apoptotic agents (z-VAD-fmk, Q-VD-OPh), and metabolic inhibitors (2-deoxyglucose, iodoacetic acid) at optimized concentrations. These parameter changes enable the composition to maintain cell viability during extended transportation periods by actively counteracting oxidative stress, apoptosis, and metabolic depletion that occur over time.
Solution Approach 2:
The invention creates a composite transportation composition that integrates multiple functional components: buffering agents (Hepes, bicarbonate, phosphate), energy substrates (glucose, pyruvate, lactate), protective proteins (BSA, gelatin), and specialized additives (antioxidants, anti-apoptotic agents). This composite formulation synergistically addresses multiple stressors simultaneously, enabling reliable cell preservation during prolonged mail transportation where single-component prior art compositions fail.
2Reliability
If chemically undefined serum and animal components are included in compositions, then critical nutrients (lipids, vitamins, hormones, trace elements) are provided, but pathogen contamination and batch variability risks increase
Solution Approach 1:
The patent extracts and eliminates chemically undefined serum and animal components from the composition while retaining essential nutrients through alternative sources. Defined lipid mixtures, purified vitamins, synthetic hormones, and controlled trace element formulations replace fetal bovine serum, thereby removing pathogen contamination risks and batch variability associated with animal-derived products while maintaining nutritional support for cell viability.
Solution Approach 2:
The invention replaces expensive, variable animal serum with cost-effective, chemically defined synthetic alternatives that can be precisely controlled and sterilized. This substitution uses purified, disposable-grade reagents with known compositions, eliminating the need for serum batch testing and reducing contamination risks while maintaining nutritional functionality.
3Reliability
If high concentrations of DMSO (10%) are used as cryoprotectant, then effective cryopreservation is achieved, but cell toxicity increases compromising therapeutic suitability
Solution Approach 1:
The patent fundamentally changes the DMSO concentration parameter from the conventional 10% down to 0-5%, demonstrating that effective cryopreservation can be achieved at lower DMSO levels when combined with optimized protective proteins (5-20% BSA or 1-10% gelatin), adjusted buffering capacity, and extended pre-freezing acclimation periods. This parameter modification reduces cytotoxicity while maintaining cryopreservation effectiveness through synergistic protective mechanisms.
Solution Approach 2:
The invention introduces protective intermediaries (BSA, gelatin, antioxidants, anti-apoptotic agents) that mediate between the cryoprotectant function and cell viability. These intermediary substances provide alternative protective mechanisms that reduce dependence on high DMSO concentrations, thereby lowering toxicity while maintaining cryopreservation effectiveness through multiple protective pathways.
Data Source
AI summary
In various aspects, there are provided compositions used for the transportation and/or cryopreservation of cells, tissues or organs. The transportation and/or cryopreservation compositions comprise at least naringenin, a buffering system and a sugar component. In some embodiments, the cells, tissues or organs are human hair follicles, cells derived from human hair follicles or cells derived from urine.