Determination of dual delivery for stem cell differentiation using dexamethasone and TGF-beta3 in/on polymeric microspheres.
In this work, a cocktail of dexamethasone (Dex) and transforming growth factor-beta3 (TGF-beta3) bound with heparin in/on PLGA microspheres was investigated by local dual delivery using rabbit mesenchymal stem cells (rMSCs) for chondrogenic differentiation in in vitro and in vivo study. In this study, we proved that the microsphere constructs were capable of simultaneously releasing TGF-beta3-conjugated with cy5.5 and Dex-conjugated with FITC with approximately zero order kinetics determined by Kodak imaging and confocal laser microscope. Microsphere constructs containing TGF-beta3 and Dex showed a significantly higher number of specific lacunae phenotypes at the end of the 4 week study irrespective of the presence of dexamethasone and TGF-beta3. Thus, dual delivery of TGF and Dex can be used to engineer inflammation-free and cartilage-associate tissue in the transplanted PLGA construct into nude mouse. These heparin-bound TGF-beta3-coated and Dex-loaded PLGA microsphere constructs show promise as coatings for implantable biomedical devices to improve biocompatibility and ensure both in vitro and in vivo performance.
Park
Ji S
JS
College of Medicine, Pochon CHA University, CHA Stem Cell Institute 606-16, Yeoksam 1-dong, Kangnam-gu, Seoul 135-081, Republic of Korea.
Na
Kun
K
Woo
Dae G
DG
Yang
Han N
HN
Park
Keun-Hong
KH
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D016503:Drug Delivery Systems; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D020869:Gene Expression Profiling; D006493:Heparin / Q000378:metabolism; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D007150:Immunohistochemistry; D019344:Lactic Acid / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018613:Microscopy, Confocal; D008863:Microspheres; D011100:Polyglycolic Acid / Q000494:pharmacology*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011485:Protein Binding / Q000187:drug effects; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053782:Transforming Growth Factor beta3 / Q000494:pharmacology*; D051598:Whole Body Imaging
D053782:Transforming Growth Factor beta3; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003907:Dexamethasone; D006493:Heparin; D016650:Fluorescein-5-isothiocyanate