دورية أكاديمية
أعرض في EDS

Scaffold-mediated lentiviral transduction for functional tissue engineering of cartilage.

التفاصيل البيبلوغرافية
العنوان: Scaffold-mediated lentiviral transduction for functional tissue engineering of cartilage.
المؤلفون: Brunger JM; Departments of Orthopaedic Surgery and Cell Biology, Duke University Medical Center, Durham, NC 27710., Huynh NP, Guenther CM, Perez-Pinera P, Moutos FT, Sanchez-Adams J, Gersbach CA, Guilak F
المصدر: Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2014 Mar 04; Vol. 111 (9), pp. E798-806. Date of Electronic Publication: 2014 Feb 18.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, DC : National Academy of Sciences
مواضيع طبية MeSH: Cell Differentiation/*physiology , Chondrogenesis/*physiology , Extracellular Matrix/*physiology , Tissue Engineering/*methods , Tissue Scaffolds/*virology , Transduction, Genetic/*methods, Analysis of Variance ; Biomechanical Phenomena ; DNA Primers/genetics ; Flow Cytometry ; Gene Transfer Techniques ; Humans ; Immunohistochemistry ; Lentivirus ; Mesenchymal Stem Cells/metabolism ; Microscopy, Electron, Scanning ; Microscopy, Fluorescence ; Polyesters ; Polylysine ; Regenerative Medicine/methods ; Transforming Growth Factor beta3/genetics
مستخلص: The ability to develop tissue constructs with matrix composition and biomechanical properties that promote rapid tissue repair or regeneration remains an enduring challenge in musculoskeletal engineering. Current approaches require extensive cell manipulation ex vivo, using exogenous growth factors to drive tissue-specific differentiation, matrix accumulation, and mechanical properties, thus limiting their potential clinical utility. The ability to induce and maintain differentiation of stem cells in situ could bypass these steps and enhance the success of engineering approaches for tissue regeneration. The goal of this study was to generate a self-contained bioactive scaffold capable of mediating stem cell differentiation and formation of a cartilaginous extracellular matrix (ECM) using a lentivirus-based method. We first showed that poly-L-lysine could immobilize lentivirus to poly(ε-caprolactone) films and facilitate human mesenchymal stem cell (hMSC) transduction. We then demonstrated that scaffold-mediated gene delivery of transforming growth factor β3 (TGF-β3), using a 3D woven poly(ε-caprolactone) scaffold, induced robust cartilaginous ECM formation by hMSCs. Chondrogenesis induced by scaffold-mediated gene delivery was as effective as traditional differentiation protocols involving medium supplementation with TGF-β3, as assessed by gene expression, biochemical, and biomechanical analyses. Using lentiviral vectors immobilized on a biomechanically functional scaffold, we have developed a system to achieve sustained transgene expression and ECM formation by hMSCs. This method opens new avenues in the development of bioactive implants that circumvent the need for ex vivo tissue generation by enabling the long-term goal of in situ tissue engineering.
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معلومات مُعتمدة: OD008586 United States OD NIH HHS; AG15768 United States AG NIA NIH HHS; R01 AR048852 United States AR NIAMS NIH HHS; R01 AG046927 United States AG NIA NIH HHS; R01 AR048182 United States AR NIAMS NIH HHS; P01 CA47741 United States CA NCI NIH HHS; AG46927 United States AG NIA NIH HHS; P01 CA047741 United States CA NCI NIH HHS; AR48852 United States AR NIAMS NIH HHS; R03 AR061042 United States AR NIAMS NIH HHS; T32 HD040372 United States HD NICHD NIH HHS; DP2 OD008586 United States OD NIH HHS; AR50245 United States AR NIAMS NIH HHS; P01 AR050245 United States AR NIAMS NIH HHS; AR061042 United States AR NIAMS NIH HHS; R01 AG015768 United States AG NIA NIH HHS; AR48182 United States AR NIAMS NIH HHS
فهرسة مساهمة: Keywords: biomaterials; chondrocyte; gene therapy; genetic engineering; regenerative medicine
المشرفين على المادة: 0 (DNA Primers)
0 (Polyesters)
0 (Transforming Growth Factor beta3)
24980-41-4 (polycaprolactone)
25104-18-1 (Polylysine)
تواريخ الأحداث: Date Created: 20140220 Date Completed: 20140508 Latest Revision: 20211021
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC3948308
DOI: 10.1073/pnas.1321744111
PMID: 24550481
قاعدة البيانات: MEDLINE
الوصف
تدمد:1091-6490
DOI:10.1073/pnas.1321744111