دورية أكاديمية
Hydrogel Encapsulation of Genome-Engineered Stem Cells for Long-Term Self-Regulating Anti-Cytokine Therapy.
العنوان: | Hydrogel Encapsulation of Genome-Engineered Stem Cells for Long-Term Self-Regulating Anti-Cytokine Therapy. |
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المؤلفون: | Collins KH; Department of Orthopaedic Surgery, Washington University, St. Louis, MO 63110, USA.; Shriners Hospitals for Children, St. Louis, MO 63110, USA.; Center of Regenerative Medicine, Washington University, St. Louis, MO 63110, USA., Pferdehirt L; Department of Orthopaedic Surgery, Washington University, St. Louis, MO 63110, USA.; Shriners Hospitals for Children, St. Louis, MO 63110, USA.; Center of Regenerative Medicine, Washington University, St. Louis, MO 63110, USA.; Department of Biomedical Engineering, Washington University, St. Louis, MO 63110, USA., Saleh LS; Department of Orthopaedic Surgery, Washington University, St. Louis, MO 63110, USA.; Shriners Hospitals for Children, St. Louis, MO 63110, USA.; Center of Regenerative Medicine, Washington University, St. Louis, MO 63110, USA., Savadipour A; Department of Orthopaedic Surgery, Washington University, St. Louis, MO 63110, USA.; Shriners Hospitals for Children, St. Louis, MO 63110, USA.; Center of Regenerative Medicine, Washington University, St. Louis, MO 63110, USA.; Department of Mechanical Engineering and Materials Science, Washington University, St. Louis, MO 63110, USA., Springer LE; Division of Rheumatology, Department of Medicine, Washington University, St. Louis, MO 63110, USA., Lenz KL; Department of Orthopaedic Surgery, Washington University, St. Louis, MO 63110, USA.; Shriners Hospitals for Children, St. Louis, MO 63110, USA., Thompson DM Jr; Department of Orthopaedic Surgery, Washington University, St. Louis, MO 63110, USA.; Shriners Hospitals for Children, St. Louis, MO 63110, USA., Oswald SJ; Department of Orthopaedic Surgery, Washington University, St. Louis, MO 63110, USA.; Shriners Hospitals for Children, St. Louis, MO 63110, USA., Pham CTN; Division of Rheumatology, Department of Medicine, Washington University, St. Louis, MO 63110, USA., Guilak F; Department of Orthopaedic Surgery, Washington University, St. Louis, MO 63110, USA.; Shriners Hospitals for Children, St. Louis, MO 63110, USA.; Center of Regenerative Medicine, Washington University, St. Louis, MO 63110, USA.; Department of Biomedical Engineering, Washington University, St. Louis, MO 63110, USA.; Department of Mechanical Engineering and Materials Science, Washington University, St. Louis, MO 63110, USA. |
المصدر: | Gels (Basel, Switzerland) [Gels] 2023 Feb 20; Vol. 9 (2). Date of Electronic Publication: 2023 Feb 20. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: MDPI AG Country of Publication: Switzerland NLM ID: 101696925 Publication Model: Electronic Cited Medium: Internet ISSN: 2310-2861 (Electronic) Linking ISSN: 23102861 NLM ISO Abbreviation: Gels Subsets: PubMed not MEDLINE |
أسماء مطبوعة: | Original Publication: Basel, Switzerland : MDPI AG, [2015]- |
مستخلص: | Biologic therapies have revolutionized treatment options for rheumatoid arthritis (RA) but their continuous administration at high doses may lead to adverse events. Thus, the development of improved drug delivery systems that can sense and respond commensurately to disease flares represents an unmet medical need. Toward this end, we generated induced pluripotent stem cells (iPSCs) that express interleukin-1 receptor antagonist (IL-1Ra, an inhibitor of IL-1) in a feedback-controlled manner driven by the macrophage chemoattractant protein-1 (Ccl2) promoter. Cells were seeded in agarose hydrogel constructs made from 3D printed molds that can be injected subcutaneously via a blunt needle, thus simplifying implantation of the constructs, and the translational potential. We demonstrated that the subcutaneously injected agarose hydrogels containing genome-edited Ccl2-IL1Ra iPSCs showed significant therapeutic efficacy in the K/BxN model of inflammatory arthritis, with nearly complete abolishment of disease severity in the front paws. These implants also exhibited improved implant longevity as compared to the previous studies using 3D woven scaffolds, which require surgical implantation. This minimally invasive cell-based drug delivery strategy may be adapted for the treatment of other autoimmune or chronic diseases, potentially accelerating translation to the clinic. |
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معلومات مُعتمدة: | AR072999 United States NH NIH HHS; AG15768 United States NH NIH HHS; T32 DK108742 United States DK NIDDK NIH HHS; R01 AG015768 United States AG NIA NIH HHS; AR073752 United States NH NIH HHS; DK108742 United States NH NIH HHS; R00 AR078949 United States AR NIAMS NIH HHS; NCI P30 CA091842 United States NH NIH HHS; R01 AR067491 United States AR NIAMS NIH HHS; T32 AR007279 United States NH NIH HHS; AR080902 United States NH NIH HHS; AR074992 United States NH NIH HHS; P50 CA094056 United States CA NCI NIH HHS; AR067491 United States NH NIH HHS; P30 AR073752 United States AR NIAMS NIH HHS; R01 AR080902 United States AR NIAMS NIH HHS; R01 AG046927 United States AG NIA NIH HHS; P30 AR074992 United States AR NIAMS NIH HHS; K99 AR078949 United States AR NIAMS NIH HHS; P50 CA094056 United States NH NIH HHS; T32 AR007279 United States AR NIAMS NIH HHS; P30 CA091842 United States CA NCI NIH HHS; AG46927 United States NH NIH HHS; T32 AR060719 United States AR NIAMS NIH HHS; AR078949 United States NH NIH HHS; R01 AR072999 United States AR NIAMS NIH HHS; T32AR060719 United States NH NIH HHS |
فهرسة مساهمة: | Keywords: autoimmune; designer cells; drug delivery; implant; induced pluripotent stem cells; rheumatoid arthritis |
تواريخ الأحداث: | Date Created: 20230224 Latest Revision: 20240427 |
رمز التحديث: | 20240427 |
مُعرف محوري في PubMed: | PMC9956980 |
DOI: | 10.3390/gels9020169 |
PMID: | 36826339 |
قاعدة البيانات: | MEDLINE |
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