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New Storage Strategy Enhances Clinical Use of Adipose Stem Cells

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Review of “Alginate-Encapsulation for the Improved Hypothermic Preservation of Human Adipose-Derived Stem Cells” from Stem Cells Translational Medicine by Stuart P. Atkinson

Due to problems with cryopreservation, many cell-based therapies use hypothermic (4°C–23°C) storage temperatures for storage and transport. While this affords better cell viability and does not involve harmful additives, we still need an effective means to enhance cell protection and elongate storage times at this temperature. 

This led Che J. Connon (Newcastle University, United Kingdom) to assess the application of alginate, a natural polysaccharide derived from seaweed that can form a biocompatible hydrogel [1], as a means to preserve the function of therapeutically relevant human adipose-derived mesenchymal stem cells (hASCs). This new study, published in Stem Cells Translational Medicine, suggests that stem cell encapsulation with alginate is a cheap and simple method to improve hypothermic preservation and improve the clinical relevance of hASC-based therapeutics [2].

Initial tests using hASCs encapsulated in alginate discs stored for 72 hours found that temperatures of around 15°C  allowed a 70% viable cell recovery, which lies within the viability specifications set by the FDA, and a low level of apoptosis. Cells stored in this manner could also reattach to tissue culture plastic and demonstrated no overt changes in their metabolic activity, cell morphology, or proliferative rate. Most importantly, the authors also found no negative effects of encapsulation on differentiation into osteogenic, adipogenic or chondrogenic lineages (See attached Figure).

While previous experiments used around 0.5 million cells per milliliter, the authors also found that alginate encapsulation mediated high cell viability using up to 4 million cells per milliliter, a more clinically relevant cell density [3]. Furthermore, they found that this storage method is compatible with serum-free cGMP-compliant media conditions using the StemPro MSC SFM medium formulated for MSC expansion. These findings all combine to promote the storage and transport of alginate-encapsulated hASCs for their eventual use in a serum-free and xeno-free, clinical setting.

This simple, effective, and low-cost storage strategy could reduce the logistical complications associated with the clinical application of stem cells. While alginate has shown some use in the preservation of human bone marrow-derived MSCs, mouse ESCs, and human limbal epithelial stem cells [4, 5], this is the first application to ASCs, a highly relevant therapeutic option. However, while alginate can now extend the storage of ASCs at hypothermic temperatures [6], the mechanism by which it exerts its effect is still under investigation by the group.

References

  1. Veiseh O, Doloff JC, Ma M, et al. Size- and shape-dependent foreign body immune response to materials implanted in rodents and non-human primates. Nat Mater 2015;14:643-651.
  2. Swioklo S, Constantinescu A, and Connon CJ Alginate-Encapsulation for the Improved Hypothermic Preservation of Human Adipose-Derived Stem Cells. Stem Cells Transl Med 2016;5:339-349.
  3. Ikebe C and Suzuki K Mesenchymal stem cells for regenerative therapy: optimization of cell preparation protocols. Biomed Res Int 2014;2014:951512.
  4. Chen B, Wright B, Sahoo R, et al. A novel alternative to cryopreservation for the short-term storage of stem cells for use in cell therapy using alginate encapsulation. Tissue Eng Part C Methods 2013;19:568-576.
  5. Wright B, Cave RA, Cook JP, et al. Enhanced viability of corneal epithelial cells for efficient transport/storage using a structurally modified calcium alginate hydrogel. Regen Med 2012;7:295-307.
  6. Hernon CA, Dawson RA, Freedlander E, et al. Clinical experience using cultured epithelial autografts leads to an alternative methodology for transferring skin cells from the laboratory to the patient. Regen Med 2006;1:809-821.