Development of a peptide-targeted, myocardial ischemia-homing, mesenchymal stem cell
| Autor: | Arnold I. Caplan, Alisher Dadabayev, Marc S. Penn, Lori Duesler, Thomas J. Kean, Randell G. Young, David J. Fink, Andrey Olenyik, Joseph Wagner, James E. Dennis |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
medicine.medical_treatment
Cell Myocardial Ischemia Pharmaceutical Science Biology Article Cell membrane Cell therapy Mice Drug Delivery Systems Drug Discovery medicine Animals Humans Cytotoxicity Cells Cultured Mesenchymal stem cell Mesenchymal Stem Cells Peptide Fragments Cell biology Mice Inbred C57BL medicine.anatomical_structure Cytokine Immunology Stem cell Peptides Homing (hematopoietic) |
| Zdroj: | J Drug Target |
| ISSN: | 1029-2330 1061-186X |
| DOI: | 10.3109/1061186x.2011.622398 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|