title: Potent trophic activity of spermidine supramolecular complexes in in vitro models.
abstract: OBJECTIVE
  To test the growth-promoting activity of the polyamine spermidine bound to various polymeric compounds in supramolecular complexes.
  
  
  METHODS
  A thiazolyl blue cell viability assay was used to determine the growth-promoting potency of spermidine-supramolecular complexes in a human skin fibroblast cell line exposed to spermidine and different spermidine-supramolecular complexes that were obtained by combining spermidine and polyanionic polymers or cyclodextrin. Reconstituted human vaginal epithelium was exposed to a specific spermidine-supramolecular complex, i.e., spermidine-hyaluronan (HA) 50, and cell proliferation was determined by Ki-67 immunohistochemical detection. Transepithelial electrical resistance and histological analysis were also performed on reconstituted human vaginal epithelium to assess tissue integrity.
  
  
  RESULTS
  The effect of spermidine and spermidine-supramolecular complexes was first tested in skin fibroblasts. Spermidine displayed a reverse dose-related mode of activity with mmol/L growth inhibition, whereas 30% stimulation over basal levels was detected at μmol/L and nmol/L levels. Novel spermidine-supramolecular complexes that formed between spermidine and polyanionic polymers, such as HA, alginate, and polymaleate, were then tested at variable spermidine concentrations and a fixed polymer level (0.1% w/v). Spermidine-supramolecular complexes stimulated the cell growth rate throughout the entire concentration range with maximal potency (up to 80%) at sub-μmol/L levels. Similar results were obtained with spermidine-(α-cyclodextrin), another type of spermidine-supramolecular complex. Moreover, the increased expression of Ki-67 in the reconstituted human vaginal epithelium exposed to spermidine-HA 50 showed that the mode of action behind the spermidine-supramolecular complexes was increased cell proliferation. Functional and morphological assessments of reconstituted human vaginal epithelium integrity did not show significant alterations after exposure to spermidine-HA, thus supporting its safety.
  
  
  CONCLUSIONS
  Spermidine found in spermidine-supramolecular complexes displayed potentiated regenerative effects. Safety data on reconstituted human vaginal epithelium suggested that assessing spermidine-supramolecular complex efficacy in atrophic disorders is justified.
authors: Carlo A Ghisalberti, Gaetano Cairo, Department of Biomedical Sciences for Health, University of Milan, 20133 Milan, Italy.
authors: Carlo A
authors: CA
authors: Ghisalberti
authors: Alberto
authors: A
authors: Morisetti
authors: Alessandro
authors: A
authors: Bestetti
authors: Gaetano
authors: G
authors: Cairo
keywords: Growth; Ki-67; Polyamines; Spermidine; Supramolecular complexes; Vaginal epithelium
references: Clin Nutr. 2005 Apr;24(2):184-97
references: 15784477
references: Autophagy. 2010 Jan;6(1):160-2
references: 20110777
references: J Cell Mol Med. 2005 Jul-Sep;9(3):623-42
references: 16202210
references: PLoS Comput Biol. 2009 Jan;5(1):e1000255
references: 19119409
references: J Biol Chem. 2010 Apr 23;285(17):12474-81
references: 20181941
references: Plant Physiol Biochem. 2010 Jul;48(7):490-5
references: 20219382
references: Nat Cell Biol. 2009 Nov;11(11):1277-8
references: 19884883
references: Altern Lab Anim. 2006 Aug;34(4):393-406
references: 16945007
references: Gut. 1999 Jan;44(1):12-6
references: 9862820
references: IUBMB Life. 2009 Sep;61(9):880-94
references: 19603518
references: J Periodontol. 2005 Mar;76(3):443-9
references: 15857080
references: Aging (Albany NY). 2011 Aug;3(8):716-32
references: 21869457
references: J Biochem. 2006 Jan;139(1):81-90
references: 16428322
references: Amino Acids. 2007 Aug;33(2):197-202
references: 17578652
references: Int J Biochem Cell Biol. 2010 Jan;42(1):39-51
references: 19643201
references: Biochem Biophys Res Commun. 2009 Mar 6;380(2):413-8
references: 19250631
references: Essays Biochem. 2009 Nov 04;46:63-76
references: 20095970
references: J Cell Mol Med. 2010 Jun;14(6B):1683-92
references: 19538475
references: Plant Physiol Biochem. 2010 Jul;48(7):506-12
references: 20159658
references: Biotechnol Adv. 2011 May-Jun;29(3):300-11
references: 21241790
references: Hum Genet. 1989 Oct;83(3):297-9
references: 2571566
references: Altern Lab Anim. 2011 Sep;39(4):317-37
references: 21942546
references: Am J Physiol Cell Physiol. 2007 Oct;293(4):C1296-301
references: 17686999
references: Invest Ophthalmol Vis Sci. 2002 Apr;43(4):1228-33
references: 11923270
references: Exp Gerontol. 2009 Nov;44(11):727-32
references: 19735716
references: Amino Acids. 2012 Feb;42(2-3):611-7
references: 21811825
references: J Cell Physiol. 2006 Mar;206(3):624-35
references: 16206250
references: Nat Cell Biol. 2009 Nov;11(11):1305-14
references: 19801973
references: Biochem Soc Trans. 2003 Apr;31(2):366-70
references: 12653640
references: Tanpakushitsu Kakusan Koso. 2009 Nov;54(14):1837-41
references: 19894584