Published online Aug 26, 2013. doi: 10.4331/wjbc.v4.i3.71
Revised: July 3, 2013
Accepted: July 23, 2013
Published online: August 26, 2013
AIM: 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.
CONCLUSION: 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.
Core tip: Previous in vitro studies showed that spermidine may have different, or even opposite, effects on cell survival, leading to either proliferation or apoptosis depending on a variety of factors. We showed that the inclusion of spermidine in supramolecular complexes with various polymers optimized its use for regenerative purposes. Spermidine-supramolecular complexes stimulated cell proliferation but did not cause significant alterations to vaginal tissue integrity. These results suggest that growth pathways in senescent or damaged tissues may be activated by the controlled release of spermidine from spermidine-supramolecular complexes to provide a faster recovery.