title: The 6-chromanol derivate SUL-109 enables prolonged hypothermic storage of adipose tissue-derived stem cells.
abstract: Encouraging advances in cell therapy research with adipose derived stem cells (ASC) require an effective short-term preservation method that provides time for quality control and transport of cells from their manufacturing facility to their clinical destination. Hypothermic storage of cells in their specific growth media offers an alternative and simple preservation method to liquid nitrogen cryopreservation or commercial preservation fluids for short-term storage and transport. However, accumulation of cell damage during hypothermia may result in cell injury and death upon rewarming through the production of excess reactive oxygen species (ROS). Here, the ability of the cell culture medium additive SUL-109, a modified 6-chromanol, to protect ASC from hypothermia and rewarming damage is examined. SUL-109 conveys protective effects against cold-induced damage in ASC as is observed by preservation of cell viability, adhesion properties and growth potential. SUL-109 does not reduce the multilineage differentiation capacity of ASC. SUL-109 conveys its protection against hypothermic damage by the preservation of the mitochondrial membrane potential through the activation of mitochondrial membrane complexes I and IV, and increases maximal oxygen consumption in FCCP uncoupled mitochondria. Consequently, SUL-109 alleviates mitochondrial ROS production and preserves ATP production. In summary, here we describe the generation of a single molecule cell preservation agent that protects ASC from hypothermic damage associated with short-term cell preservation that does not affect the differentiation capacity of ASC.
authors.affiliation: Cardiovascular Regenerative Medicine, Dept. Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Hanzeplein 1 (EA11), 9713GZ, Groningen, The Netherlands.
authors.forename: Ghazaleh
authors.initials: G
authors.lastname: Hajmousa
authors.affiliation: Sulfateq B.V., Admiraal de Ruyterlaan 5, 9726GN, Groningen, The Netherlands.
authors.forename: Pieter
authors.initials: P
authors.lastname: Vogelaar
authors.affiliation: Cardiovascular Regenerative Medicine, Dept. Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Hanzeplein 1 (EA11), 9713GZ, Groningen, The Netherlands.
authors.forename: Linda A
authors.initials: LA
authors.lastname: Brouwer
authors.affiliation: Sulfateq B.V., Admiraal de Ruyterlaan 5, 9726GN, Groningen, The Netherlands.
authors.forename: Adrianus C
authors.initials: AC
authors.lastname: van der Graaf
authors.affiliation: Dept. Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Hanzeplein 1 (EB71), 9713GZ, Groningen, The Netherlands.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Henning
authors.affiliation: Cardiovascular Regenerative Medicine, Dept. Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Hanzeplein 1 (EA11), 9713GZ, Groningen, The Netherlands; Sulfateq B.V., Admiraal de Ruyterlaan 5, 9726GN, Groningen, The Netherlands. Electronic address: g.krenning@umcg.nl.
authors.forename: Guido
authors.initials: G
authors.lastname: Krenning
mesh_terms: D000273:Adipose Tissue / Q000737:chemistry / Q000166:cytology*; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002470:Cell Survival; D002478:Cells, Cultured; D002839:Chromans / Q000737:chemistry*; D015925:Cryopreservation / Q000379:methods*; D003451:Cryoprotective Agents / Q000737:chemistry*; D006801:Humans; D019188:Organ Preservation Solutions / Q000737:chemistry*; D013234:Stem Cells / Q000737:chemistry* / Q000166:cytology*
chemical_list: D002839:Chromans; D003451:Cryoprotective Agents; D019188:Organ Preservation Solutions; C029141:2,2,5,7,8-pentamethyl-1-hydroxychroman
keywords: Adipose tissue-derived stem cells (ASC); Chromanol; Cold storage; Hypothermia; Mitochondrial damage