title: Development of a peptide-targeted, myocardial ischemia-homing, mesenchymal stem cell.
abstract: Directing stem cells to the heart is critical in producing an effective cell therapy for myocardial infarction (MI). Mesenchymal stem cells (MSCs) offer an exquisite drug delivery platform with environment-sensing cytokine release and MSCs have shown therapeutic potential in MI. Peptide-based targeting offers a novel method to increase cell homing, wherein MI-specific peptides, identified by phage display, are synthesized with a palmitic acid tail to facilitate cell membrane integration. Phage-peptides were screened in a mouse MI model and four peptides (CRPPR, CRKDKC, KSTRKS, and CARSKNKDC) were selected and synthesized as palmitated derivatives for further investigation. Cell coating was optimized and coating persistence and cytotoxicity were evaluated. MSCs were coated with peptides, injected into mice with MI, and MSCs in the heart quantified. Greater numbers of MSCs were found in heart of animals treated with the peptide-coated MSCs compared to uncoated controls. MSC numbers had positive correlation with MI severity in peptide-coated cells but a negative correlation in MSCs alone. A transient cell coating ("painting") method has been developed that labels cells efficiently, non-toxically and increases cell localization in MI hearts.
authors: Orthopaedics Department, Case Western Reserve University, Cleveland, OH, USA. tkean@benaroyaresearch.org
authors: Thomas J
authors: TJ
authors: Kean
authors: Lori
authors: L
authors: Duesler
authors: Randell G
authors: RG
authors: Young
authors: Alisher
authors: A
authors: Dadabayev
authors: Andrey
authors: A
authors: Olenyik
authors: Marc
authors: M
authors: Penn
authors: Joseph
authors: J
authors: Wagner
authors: David J
authors: DJ
authors: Fink
authors: Arnold I
authors: AI
authors: Caplan
authors: James E
authors: JE
authors: Dennis
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016503:Drug Delivery Systems / Q000379:methods / Q000639:trends*; D055808:Drug Discovery / Q000639:trends; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D010446:Peptide Fragments / Q000008:administration & dosage / Q000378:metabolism; D010455:Peptides / Q000008:administration & dosage* / Q000378:metabolism
chemical_list: D010446:Peptide Fragments; D010455:Peptides