L. D’Souza, R. Patel, H. Varga, and C. Morley
Correspondence: The StemX Research Group, SXR Laboratories
Full Article
Abstract
This small-scale feasibility evaluation assessed the stability and viability of cryopreserved mesenchymal stromal cells (MSCs) during short-distance transport between a UK manufacturing facility and a clinical site under current Advanced Therapy Medicinal Product (ATMP) regulatory conditions.
Cells were prepared under Good Manufacturing Practice (GMP), stored in vapour-phase liquid nitrogen, and transferred on dry shippers in compliance with MHRA and HTA requirements. Post-transport viability, morphology, and surface marker expression were compared to pre-shipment reference samples.
Viability remained above 91% after 48 hours, with no significant alteration in CD73, CD90, or CD105 expression. The study supports the operational feasibility of small-scale MSC transfers under UK governance frameworks.
1. Introduction
Mesenchymal stromal cells (MSCs) are increasingly used in cell-based investigational therapies due to their immunomodulatory and regenerative properties. However, early-phase studies in the UK often face logistical and regulatory challenges, particularly during inter-site transport of cryopreserved cell products.
Transport processes must align with the MHRA’s Good Manufacturing Practice (GMP) standards, the Human Tissue Authority (HTA) licensing requirements, and Health Research Authority (HRA) ethical oversight where applicable.
This evaluation examined whether cryopreserved MSCs retained acceptable viability and phenotypic characteristics following short-term transport under conditions representative of NHS-based early-phase translational studies. The activity was reviewed by the Health Research Authority (HRA) (Ref: 25/LO/0187) and conducted under MHRA non-CTIMP guidance as a non-clinical feasibility project. Cell storage and handling were performed under HTA licence 22542, and all data were processed in compliance with UK GDPR.
2. Methods
Design and setting:
Observational laboratory-based feasibility study conducted at the SXR Cellular Processing Facility and the affiliated NHS clinical site between May and September 2025.
Cell source and preparation:
Human bone marrow-derived MSCs were obtained from consented donors under HTA-approved protocols. Cells were expanded in α-MEM medium with 10% FBS and cryopreserved at 1×106 cells/mL using 10% DMSO. Cryovials were stored in vapour-phase liquid nitrogen until shipment.
Transport protocol:
Samples were packed in validated dry shippers (−150°C vapour-phase) and transported approximately 35 miles by a licensed courier under UN3373 Biological Substance Category B compliance. Transit times were between 6 and 48 hours. Temperature and shock sensors monitored stability throughout.
Post-transport testing:
Upon arrival, vials were thawed in a 37°C water bath and washed twice with sterile saline. Cell viability assessed by trypan blue exclusion and flow cytometry (Annexin V/PI). Phenotype evaluated by flow cytometry for CD73, CD90, CD105, and negative markers CD34/CD45. Morphology reviewed under phase-contrast microscopy.
Statistical analysis:
Comparisons between pre- and post-transport samples used paired t-tests (SPSS v28). Significance defined as p < 0.05.
3. Results
Mean post-thaw viability remained above 91.3% ± 3.2% after 48 hours of storage in dry shippers, compared to 93.1% ± 2.9% pre-shipment (p = 0.21). No significant change was observed in surface marker expression (CD73+, CD90+, CD105+) or in negative lineage markers (CD34−, CD45−). Morphology remained fibroblast-like, with no observable changes in adherence or confluence patterns during recovery. Temperature monitoring confirmed a continuous vapour-phase environment (−145°C to −160°C). No regulatory deviations, labelling errors, or courier incidents occurred during the trial period.
4. Discussion
This small-scale feasibility study demonstrated that cryopreserved MSCs can be transported safely between UK sites while maintaining viability and phenotypic integrity. The findings support the practical implementation of early-phase ATMP handling under the MHRA’s UK Good Manufacturing Practice framework and HTA tissue storage licensing.
The project also illustrated the value of close coordination between manufacturing, clinical, and quality assurance teams to ensure adherence to documentation and traceability standards. The data are modest but provide reassurance that small-scale transfers within the NHS infrastructure can be achieved without quality compromise. Future studies could evaluate longer transport times and multi-site coordination to inform national ATMP logistics frameworks.
5. Limitations
- Conducted using a single cell source and short transport distance.
- No assessment of long-term differentiation potential.
- Results may not apply to other cell types or manufacturing methods.
- Environmental stress limited to vapour-phase nitrogen; ambient-temperature transfers not tested.
6. Conclusion
Cryopreserved MSC transport over short distances within the UK maintained high viability and stable phenotype when performed under regulated GMP and HTA conditions. These results confirm the feasibility of small-scale logistics supporting early translational cell therapy work under existing UK regulatory oversight.
7. References
StemX Research Group. Internal Cell Logistics Validation Report SXR-CT-2025-10. 2025.
MHRA. Guidance on Good Manufacturing Practice for Advanced Therapy Medicinal Products. London; 2025.
Health Research Authority. UK Policy Framework for Health and Social Care Research. London; 2024.
Human Tissue Authority. Codes of Practice and Standards, Version 4. London; 2025.
NHS England. Advanced Therapy Medicinal Products Strategy. London; 2024.