Neuroprotective Stem Cell Secreted Peptides

Göteborg, Sweden -

Stem cells grown in culture are known to secrete a variety of factors, some of which have ability to protect tissue from apoptosis.  For example, media from adipose stem cells cultured in hypoxia has been demonstrated to inhibit neonatal ischemic injury in a mouse model of cerebral palsy.  Patent #5,316,937 describes a stem cell-like cell line that secretes factors in conditioned media capable of repairing colonic crypt cells.  Conditioned media of varous stem cell types has been demonstrated to not only possess regenerative activities but also immune modulatory features.  Indeed in clinical situations such as inhibition of multiple sclerosis by fat stem cells, the effects of soluble factors have been postulated.

A recent paper (Faijerson et al. Adult neural stem/progenitor cells reduce NMDA-induced excitotoxicity via the novel neuroprotective peptide pentinin. J Neurochem 2009 May;109(3):858-66) sought to identify what some of the soluble factors generated by stem cells were.  Interestingly instead of doing conventional proteomics approaches, they used a metabolomics based assay.

The investigators first showed that media conditioned by adult hippocampal stem/progenitor cells significantly reduced cell death following 24 h of exposure to 10 microM NMDA (model of excitotoxic death).

Using mass spectrometric analysis of the conditioned medium, they identified a pentameric peptide fragment that corresponded to residues 26-30 of the insulin B chain.  This peptide they named 'pentinin'.

To demonstrate the neuroprotective activities of pentinin, when 100 pM of synthetic pentinin was added to the excitotoxicity assay, the number of mature and immature neurons killed by NMDA was significantly reduced in the dentate gyrus.

Metabolomic based approaches, such as ones being pioneered by Gabriela Cezar at Stemina, are sure to develop many more exciting new peptides/metabolites useful in regenerative medicine.