Abstract
Encouraging advances in cell therapies have produced a requirement for an effective short-term cell preservation method, enabling time for quality assurance testing and transport to their clinical destination. Low temperature pausing of cells offers many advantages over cryopreservation, including the ability to store cells at scale, reduced cost and a simplified procedure with increased reliability. This review will focus on the importance of developing a short-term cell preservation platform as well highlighting the major successes of cell pausing and the key challenges which need addressing, to enable application of the process to therapeutically relevant cells.
Similar content being viewed by others
References
Anderson RV, Siegman MG, Balaban RS, Ceckler TL, Swain JA (1992) Hyperglycemia increases cerebral intracellular acidosis during circulatory arrest. Ann Thorac Surg 54:1126–1130
Celartia (2012). PetakaG3. http://petaka.com/. Accessed 14 June 2012
Chen B, Wright B, Sahoo R, Connon CJ (2013) A novel alternative to cryopreservation for the short-term storage of stem cells for use in cell therapy using alginate encapsulation. J Tissue Eng 19:568–576
Coopman K (2011) Large-scale compatible methods for the preservation of human embryonic stem cells: current perspectives. Biotechnol Prog 27:1511–1521
Cox MA, Kastrup J, Hrubiško M (2012) Historical perspectives and the future of adverse reactions associated with haemopoietic stem cells cryopreserved with dimethyl sulfoxide. Cell Tissue Bank 13:203–215
Fox SR, Yap MX, Yap MGS, Wang DIC (2005) Active hypothermic growth: a novel means for increasing total interferon-gamma production by Chinese-hamster ovary cells. Biotechnol Appl Biochem 41:265–272
Fujita J (1999) Cold shock response in mammalian cells. J Mol Microbiol Biotechnol 1:243–255
Gherna RL (1999) Culture preservation, bacteria, fungi, yeast, and cell lines. In: Flickinger MC, Drew SW (eds) Encyclopedia of bio-process technology: fermentation, biocatalysis and bioseparation. Wiley, New York, pp 786–793
Ginis I, Grinblat B, Shirvan MH (2012) Evaluation of bone marrow-derived mesenchymal stem cells after cryopreservation and hypothermic storage in clinically safe medium. Tissue Eng 18:453–463
Harel A (2013) Cryopreservation and cell banking for autologous mesenchymal stem cell-based therapies. Cell Tissue Transplant Ther 2013:1–7
Heidemann R, Lünse S, Tran D, Zhang C (2010) Characterization of cell-banking parameters for the cryopreservation of mammalian cell lines in 100-mL cryobags. Biotechnol Prog 26:1154–1163
Heng BC, Vinoth KJ, Liu H, Hande MP, Cao T (2006) Low temperature tolerance of human embryonic stem cells. Int J Med Sci 3:124–129
Högman CF (1998) Preparation and preservation of red cells. Vox Sang 74:177–187
Holovati JL, Acker JP (2011) Emerging role for use of liposomes in the biopreservation of red blood cells. Transfus Med Hemother 38:99–106
Hope A, Milijan E, Sinden J (2011) Cellular composition for use in therapy. US Patent 2367419
Hunt CJ (2011) Cryopreservation of human stem cells for clinical application: a review. Transfus Med Hemother 38:107–123
Hunt L, Hacker DL, Grosjean F, De Jesus M, Uebersax L, Jordan M, Wurm FM (2005) Low-temperature pausing of cultivated mammalian cells. Biotechnol Bioeng 89:157–163
Jamieson NV, Sundberg R, Lindell S, Claesson K, Moen J, Vreugdenhil PK, Wight DG, Southard JH, Belzer FO (1988) Preservation of the canine liver for 24–48 h using simple cold storage with UW solution. Transplantation 46:517–522
Kleeberger CA, Lyles RH, Margolick JB, Rinaldo CR, Phair JP, Giorgi JV (1999) Viability and recovery of peripheral blood mononuclear cells cryopreserved for up to 12 years in a multicenter study. Clin Diagn Lab Immunol 6:14–19
Kotobuki N, Hirose M, Machida H, Katou Y, Muraki K, Takakura Y, Ohgushi H (2005) Viability and osteogenic potential of cryopreserved human bone marrow-derived mesenchymal cells. Tissue Eng 11:663–673
Li Y, Tan J-C, Li L-S (2010) Comparison of three methods for cryopreservation of human embryonic stem cells. Fertil Steril 93:999–1005
Mahler S, Desille M, Frémond B, Chesné C, Guillouzo A, Campion J-P, Clément B (2003) Hypothermic storage and cryopreservation of hepatocytes: the protective effect of alginate gel against cell damages. Cell Transplant 12:579–592
Marx J (2006) Rosen’s emergency medicine: concepts and clinical practice, 7th edn. Mosby/Elsevier, Philadelphia, p 2239
Mason C, Dunnill P (2009) Quantities of cells used for regenerative medicine and some implications for clinicians and bioprocessors. Regen Med 4:153–157
Mason C, Manzotti E (2010) Regenerative medicine cell therapies: numbers of units manufactured and patients treated between 1988 and 2010. Regen Med 5:307–313
Mathew AJ, Van Buskirk RG, Baust JG (2002) Improved hypothermic preservation of human renal cells through suppression of both apoptosis and necrosis. Cell Preserv Technol 1:239–253
Mathew AJ, Baust JM, Van Buskirk RG, Baust JG (2004) Cell preservation in reparative and regenerative medicine: evolution of individualized solution composition. Tissue Eng 10:1662–1671
Mazur P (1984) Freezing of living cells: mechanisms and implications. Am J Physiol 247:C125–C142
Meng Q (2003) Hypothermic preservation of hepatocytes. Biotechnol Prog 19:1118–1127
Merten OW (1999) Safety issues of animal products used in serum-free media. Dev Biol Stand 99:167–180
Mirabet V, Alvarez M, Solves P, Ocete D, Gimeno C (2012) Use of liquid nitrogen during storage in a cell and tissue bank: contamination risk and effect on the detectability of potential viral contaminants. Cryobiology 64:121–123
Morel P, Moss A, Schlumpf R, Nakhleh R, Lloveras JK, Field MJ, Condie R, Matas AJ, Sutherland DE (1992) 72-h preservation of the canine pancreas: successful replacement of hydroxyethylstarch by dextran-40 in UW solution. Transplant Proc 24:791–794
Mummery CL (2005) Cardiology: solace for the broken-hearted? Nature 433:585–587
Nikolaev NI, Liu Y, Hussein H, Williams DJ (2012) The sensitivity of human mesenchymal stem cells to vibration and cold storage conditions representative of cold transportation. J R Soc Interface 9:2503–2515
Nishiyama H, Higashitsuji H, Yokoi H, Itoh K, Danno S, Matsuda T, Fujita J (1997) Cloning and characterization of human CIRP (cold-inducible RNA-binding protein) cDNA and chromosomal assignment of the gene. Gene 204:115–120
Rauen U, Petrat F, Li T, De Groot H (2000) Hypothermia injury/cold-induced apoptosis—evidence of an increase in chelatable iron causing oxidative injury in spite of low O2-/H2O2 formation. FASEB J 14:1953–1964
Roobol A, Carden MJ, Newsam RJ, Smales CM (2009) Biochemical insights into the mechanisms central to the response of mammalian cells to cold stress and subsequent rewarming. FEBS J 276:286–302
Santos NC, Figueira-Coelho J, Martins-Silva J, Saldanha C (2003) Multidisciplinary utilization of dimethyl sulfoxide: pharmacological, cellular, and molecular aspects. Biochem Pharmacol 65:1035–1041
Scott KL, Lecak J, Acker JP (2005) Biopreservation of red blood cells: past, present, and future. Transfus Med Rev 19:127–142
Stroemer P, Patel S, Hope A, Oliveira C, Pollock K, Sinden J (2009) The neural stem cell line CTX0E03 promotes behavioral recovery and endogenous neurogenesis after experimental stroke in a dose-dependent fashion. Neurorehabil Neural Repair 23:895–909
Taylor MJ (1982) The role of pH and buffer capacity in the recovery of function of smooth muscle cooled to −13 °C in unfrozen media. Cryobiology 19:585–601
Taylor MJ, Pignat Y (1982) Practical acid dissociation constants, temperature coefficients, and buffer capacities for some biological buffers in solutions containing dimethyl sulfoxide between 25 and −12 °C. Cryobiology 19:99–109
Terry C, Dhawan A, Mitry RR, Hughes RD (2006) Cryopreservation of isolated human hepatocytes for transplantation: state of the art. Cryobiology 53:149–159
TiGenix S.A.U. (2013) Cx621-0101 Phase 1 Clinical trial in healthy volunteers to evaluate the feasibility and safety of the intralymphatic administration technique of expanded allogeneic adipose-derived stem cells (eASCs) In: ClincialTrials.gov [Internet]. National Library of Medicine (US), Bethesda, MD. http://clinicaltrials.gov/show/NCT01743222 NLM Identifier: NCT01743222. Accessed 20 Apr 2013
Unger C, Skottman H, Blomberg P, Dilber MS, Hovatta O (2008) Good manufacturing practice and clinical-grade human embryonic stem cell lines. Hum Mol Genet 17:R48–R53
Watanabe K, Ueno M, Kamilya D, Nishiyama A, Matsumara M, Wataya T, Takahashi JB, Nishikawa S, Nishikawa S-I, Mugurama K, Sasai Y (2007) A ROCK inhibitor permits survival of dissociated human embryonic stem cells. Nat Biotechnol 25:681–686
Wise H, Abel PW, Cawkill D (2009) Use of reduced temperature cell pausing to enhance flexibility of cell-based assays. J Biomol Screen 14:716–722
Xu X, Cowley S, Flaim CJ, James W, Seymour L, Cui Z (2010) The roles of apoptotic pathways in the low recovery rate after cryopreservation of dissociated human embryonic stem cells. Biotechnol Prog 26:827–837
Zhou Y, Guan X, Zhu Z, Gao S, Zhang C, Li C, Zhou K, Hou W, Yu H (2011) Osteogenic differentiation of bone marrow-derived mesenchymal stromal cells on bone-derived scaffolds: effect of microvibration and role of ERK1/2 activation. Eur Cells Mater 22:12–25
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Robinson, N.J., Picken, A. & Coopman, K. Low temperature cell pausing: an alternative short-term preservation method for use in cell therapies including stem cell applications. Biotechnol Lett 36, 201–209 (2014). https://doi.org/10.1007/s10529-013-1349-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10529-013-1349-5