title: Dental mesenchymal stem cells encapsulated in an alginate hydrogel co-delivery microencapsulation system for cartilage regeneration.
abstract: Dental-derived mesenchymal stem cells (MSCs) are promising candidates for cartilage regeneration, with a high capacity for chondrogenic differentiation. This property helps make dental MSCs an advantageous therapeutic option compared to current treatment modalities. The MSC delivery vehicle is the principal determinant for the success of MSC-mediated cartilage regeneration therapies. The objectives of this study were to: (1) develop a novel co-delivery system based on TGF-β1 loaded RGD-coupled alginate microspheres encapsulating periodontal ligament stem cells (PDLSCs) or gingival mesenchymal stem cells (GMSCs); and (2) investigate dental MSC viability and chondrogenic differentiation in alginate microspheres. The results revealed the sustained release of TGF-β1 from the alginate microspheres. After 4 weeks of chondrogenic differentiation in vitro, PDLSCs and GMSCs as well as human bone marrow mesenchymal stem cells (hBMMSCs) (as positive control) revealed chondrogenic gene expression markers (Col II and Sox-9) via qPCR, as well as matrix positively stained by Toluidine Blue and Safranin-O. In animal studies, ectopic cartilage tissue regeneration was observed inside and around the transplanted microspheres, confirmed by histochemical and immunofluorescent staining. Interestingly, PDLSCs showed more chondrogenesis than GMSCs and hBMMSCs (p<0.05). Taken together, these results suggest that RGD-modified alginate microencapsulating dental MSCs make a promising candidate for cartilage regeneration. Our results highlight the vital role played by the microenvironment, as well as value of presenting inductive signals for viability and differentiation of MSCs.
authors.affiliation: Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, Los Angeles, CA 90033, USA. Electronic address: moshaver@usc.edu.
authors.forename: Alireza
authors.initials: A
authors.lastname: Moshaverinia
authors.forename: Xingtian
authors.initials: X
authors.lastname: Xu
authors.forename: Chider
authors.initials: C
authors.lastname: Chen
authors.forename: Kentaro
authors.initials: K
authors.lastname: Akiyama
authors.forename: Malcolm L
authors.initials: ML
authors.lastname: Snead
authors.forename: Songtao
authors.initials: S
authors.lastname: Shi
mesh_terms: D000293:Adolescent; D000328:Adult; D000464:Alginates / Q000737:chemistry*; D000818:Animals; D002356:Cartilage / Q000187:drug effects / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D060833:Cellular Microenvironment / Q000187:drug effects; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020219:Chondrogenesis / Q000187:drug effects; D004339:Drug Compounding; D016503:Drug Delivery Systems; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D008863:Microspheres; D010519:Periodontium / Q000166:cytology*; D012038:Regeneration / Q000187:drug effects / Q000502:physiology*; D040521:Subcutaneous Tissue / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D055815:Young Adult
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D053773:Transforming Growth Factor beta1; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D020723:Glucuronic Acid
keywords: Alginate hydrogel; Cartilage regeneration; Dental mesenchymal stem cells; RGD tripeptide; Tissue engineering
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