In this series we review new interesting products and techniques for clinical-grade cell processing and manufacturing. Cell processing devices, cultureware, bioreactors, GMP-grade reagents, cell separation techniques… Read Clinical Cell Processing News!
1. Alginate encapsulation for short-term storage of cell products under ambient conditions (Tissue Eng Part C)
The present study aims to use semi-permeable alginate hydrogels (cross-linked by strontium) to encapsulate, store and release stem cells, in order to replace the conventional cryo-preservation method for the transport of therapeutic cells within world-wide distribution time-frame. Human mesenchymal stem cell (hMSC) and mouse embryonic stem cells (mESC) were successfully stored inside alginate hydrogels for 5 days under ambient conditions in an air-tight environment (sealed cryo-vial).
2. Validation of xeno-free enzymatic products for isolation of adipose stromal cells (Tissue Eng Part C)
The objective of this study was to determine the suitability and efficacy of various alternative enzymatic products, CLS1 (Worthington), CLSAFA (Worthington), NB4 (SERVA), and Liberase (Roche), for the digestion of adipose tissue and subsequent isolation of ASCs, assessing cells functionality concerning their proliferation and differentiation ability.
We concluded that clinical grade products can replace current research grade products effectively in our cell isolation protocols without any negative effect in the yield or function of human ASCs.
3. Validation of CryoStor CS10 (BioLife Solutions) for cord blood cryopreservation (Transfusion)
Postthaw recoveries with CryoStor were equivalent to or slightly better than with the in-house cryopreservation solution. CryoStor also provides several advantages including reduced processing time, formulation consistency, and reduced DMSO in the frozen product (≤5%)
4. Validation of SmartWashTM (BioSafe) – automated device for washing of cryopreserved blood stem cell products (ASH 2012 abstract)
SmartWash™ is an efficient and safe automated method to wash thawed PBSC grafts in a closed, clinical-grade system. Its feasibility and reproducibility was confirmed in an international, multicenter, clinical study.
5. New filtration device for cord blood processing (Int J Lab Hematol)
We developed a novel filtration system using a nonchemical-coated and nonwoven polyester fabric filter, which traps cells through affinity and does not require centrifugation or potentially toxic chemicals.
6. Concentrating of osteoprogenitors in bone marrow aspirate via filtration (Cytotherapy)
BMA was filtered to achieve a mean 4.2-fold reduction in volume with a corresponding enrichment of viable and functional osteoprogenitors, indicated by flow cytometry and assays for colony formation. Enhanced osteogenic and chondrogenic differentiation was observed using concentrated aspirate and enhanced cell-seeding efficiency onto allogeneic bone graft as an effect of osteoprogenitor concentration relative specifically to the concentration of erythrocytes in the aspirate.
7. Validation of new protocol for cryopreservation of ex vivo expanded cord blood CD34+ cells (Transfusion)
Cryopreservation and thawing of expanded CB cells using the “standard” procedure (HSA-DMSO) reduced recovery of the CPs (40%) and HSCs (drastically decreasing engraftment capacity). HP01-based protocol resulted in improvement of preservation of both CPs (>60%) and HSCs (nonaltered engraftment capacities).
8. Optimization of clinical expansion and manufacturing of gene-modified T-cells (ASH 2012 abstract)
Taken together the total T cell fold expansion (93) and the enrichment for the transgene (2.4±1.2), we calculate a 223.5±111.6 fold expansion of CAR T cells with 10 days of culture. Importantly we demonstrated the robustness of this manufacture process by successfully extending this approach to other CAR T cell products.
9. New device for non-enzymatic isolation of adipose stromal cells (Cell Transplant)
Here, we present an innovative system, named Lipogems, providing a non-expanded, ready-to-use fat product. The system uses mild mechanical forces in a completely closed system, avoiding enzymes, additives and other manipulations.
10. Cell therapy devices – approved or in development:
Bioreactor for NurOwn stem cell therapy (BrainStorm)
Point-of-care cell thawing device (Pluristem)
Angel cPRP system approval by FDA (Cytomedix)
Angel cPRP system CE mark approval (Cytomedix)