Alpha 7 subunit of nAChR regulates migration of human mesenchymal stem cells.
The efficient migration of mesenchymal stem cells (MSCs) to diseased tissues is required for the fulfillment of their regenerative potential. Recruitment of circulating cells into the damaged tissues is regulated by a complex network, which includes the non-neural cholinergic system. We found that human MSCs (hMSCs) express nicotinic acetylcholine receptor subunits alpha 7, beta 2 and beta 4. The receptor agonist nicotine caused calcium (Ca(++)) influx into hMSCs suggesting that the calcium ion channel alpha 7 homopolymer mediated this response. While high concentrations of nicotine (10(5)M) induced hMSC apoptosis, physiological concentrations (10(7)M) did not interfere with cell survival. At non-toxic concentrations, nicotine increased spontaneous migration of hMSCs, whereas chemotaxis of hMSCs toward C3a and bFGF in vitro and migration of intravenously infusion hMSCs into bone marrow and spleen in vivo were inhibited. The antagonist for the alpha 7 homopolymer, bungarotoxin, blocked the inhibitory effect of nicotine on chemotactic factor-induced migration of hMSCs. These findings reveal an involvement of the non-neural cholinergic system in regulation of hMSC migration.
Schraufstatter
Ingrid U
IU
Torrey Pines Institute for Molecular Studies, San Diego, CA 92121, USA.
DiScipio
Richard G
RG
Khaldoyanidi
Sophia K
SK
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D018925:Chemokines / Q000494:pharmacology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009538:Nicotine / Q000378:metabolism / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000378:metabolism / Q000494:pharmacology; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D064569:alpha7 Nicotinic Acetylcholine Receptor
D002118:Calcium; D018925:Chemokines; D009538:Nicotine; D018722:Nicotinic Agonists; D021122:Protein Subunits; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C579167:Chrna7 protein, human; C579166:Chrna7 protein, mouse