دورية أكاديمية
Hydrogel-Embedded Poly(Lactic- co -Glycolic Acid) Microspheres for the Delivery of hMSC-Derived Exosomes to Promote Bioactive Annulus Fibrosus Repair.
العنوان: | Hydrogel-Embedded Poly(Lactic- co -Glycolic Acid) Microspheres for the Delivery of hMSC-Derived Exosomes to Promote Bioactive Annulus Fibrosus Repair. |
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المؤلفون: | DiStefano TJ; Leni and Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Vaso K; Department of Chemical Engineering, The Cooper Union for the Advancement of Science and Art, New York, NY, USA., Panebianco CJ; Leni and Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Danias G; Leni and Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Chionuma HN; Leni and Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Kunnath K; Department of Chemical Engineering, New Jersey Institute of Technology, Newark, NJ, USA., Karoulias SZ; Leni and Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Wang M; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Xu P; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Davé RN; Department of Chemical Engineering, New Jersey Institute of Technology, Newark, NJ, USA., Sahoo S; Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Weiser JR; Department of Chemical Engineering, The Cooper Union for the Advancement of Science and Art, New York, NY, USA., Iatridis JC; Orthopaedic Research Laboratories, Leni and Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, New York, NY, USA. |
المصدر: | Cartilage [Cartilage] 2022 Jul-Sep; Vol. 13 (3), pp. 19476035221113959. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural |
اللغة: | English |
بيانات الدورية: | Publisher: Sage Country of Publication: United States NLM ID: 101518378 Publication Model: Print Cited Medium: Internet ISSN: 1947-6043 (Electronic) Linking ISSN: 19476035 NLM ISO Abbreviation: Cartilage Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Los Angeles : Sage |
مواضيع طبية MeSH: | Annulus Fibrosus* , Exosomes*/genetics , Exosomes*/metabolism , Mesenchymal Stem Cells*/metabolism, Glycols/metabolism ; Humans ; Hydrogels ; Microspheres ; Polylactic Acid-Polyglycolic Acid Copolymer/metabolism |
مستخلص: | Objective: Intervertebral disk degeneration is a prevalent postoperative complication after discectomy, underscoring the need to develop preventative and bioactive treatment strategies that decelerate degeneration and seal annulus fibrosus (AF) defects. Human mesenchymal stem cell-derived exosomes (MSC-Exos) hold promise for cell-free bioactive repair; however, their ability to promote AF repair is poorly understood. The objective of this study was to evaluate the ability of MSC-Exos to promote endogenous AF repair processes and integrate MSC-Exos within a biomaterial delivery system. Design: We characterize biophysical and biochemical properties of normoxic (Nx) and hypoxic (Hx) preconditioned MSC-Exos from young, healthy donors and examine their effects on AF cell proliferation, migration, and gene expression. We then integrate a poly(lactic- co -glycolic acid) microsphere (PLGA µSphere) delivery platform within an interpenetrating network hydrogel to facilitate sustained MSC-Exo delivery. Results: Hx MSC-Exos led to a more robust response in AF cell proliferation and migration than Nx MSC-Exos and was selected for a downstream protection experiment. Hx MSC-Exos maintained a healthy AF cell phenotype under a TNFα challenge in vitro and attenuated catabolic responses. In all functional assays, AF cell responses were more sensitive to Hx MSC-Exos than Nx MSC-Exos. PLGA µSpheres released MSC-Exos over a clinically relevant timescale without affecting hydrogel modulus or pH upon initial embedment and µSphere degradation. Conclusions: This MSC-Exo treatment strategy may offer benefits of stem cell therapy without the need for exogenous stem cell transplantation by stimulating cell proliferation, promoting cell migration, and protecting cells from the degenerative proinflammatory microenvironment. |
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معلومات مُعتمدة: | R01 AR057397 United States AR NIAMS NIH HHS; R01 AR080096 United States AR NIAMS NIH HHS; T32 GM062754 United States GM NIGMS NIH HHS |
فهرسة مساهمة: | Keywords: drug delivery; exosomes; extracellular vesicles; hydrogels; intervertebral disk |
المشرفين على المادة: | 0 (Glycols) 0 (Hydrogels) 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer) |
تواريخ الأحداث: | Date Created: 20220830 Date Completed: 20220902 Latest Revision: 20220911 |
رمز التحديث: | 20221213 |
مُعرف محوري في PubMed: | PMC9434687 |
DOI: | 10.1177/19476035221113959 |
PMID: | 36040157 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1947-6043 |
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DOI: | 10.1177/19476035221113959 |