Persistent tailoring of MSC activation through genetic priming.
| العنوان: | Persistent tailoring of MSC activation through genetic priming. |
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| المؤلفون: | Beauregard MA; Department of Bioengineering, Rice University, Houston, TX, USA., Bedford GC; Department of Bioengineering, Rice University, Houston, TX, USA., Brenner DA; Department of Bioengineering, Rice University, Houston, TX, USA., Sanchez Solis LD; Department of Bioengineering, Rice University, Houston, TX, USA., Nishiguchi T; The Global Tuberculosis Program, Texas Children's Hospital, Immigrant and Global Health, WTS Center for Human Immunobiology, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA., Abhimanyu; The Global Tuberculosis Program, Texas Children's Hospital, Immigrant and Global Health, WTS Center for Human Immunobiology, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA., Longlax SC; The Global Tuberculosis Program, Texas Children's Hospital, Immigrant and Global Health, WTS Center for Human Immunobiology, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA., Mahata B; Department of Bioengineering, Rice University, Houston, TX, USA., Veiseh O; Department of Bioengineering, Rice University, Houston, TX, USA., Wenzel PL; Department of Integrative Biology & Pharmacology, The University of Texas Health Science Center at Houston, Houston, TX, USA.; Center for Stem Cell and Regenerative Medicine, Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USA.; Immunology Program, The University of Texas MD Anderson UTHealth Graduate School of Biomedical Sciences, Houston, TX, USA., DiNardo AR; The Global Tuberculosis Program, Texas Children's Hospital, Immigrant and Global Health, WTS Center for Human Immunobiology, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands., Hilton IB; Department of Bioengineering, Rice University, Houston, TX, USA., Diehl MR; Department of Bioengineering, Rice University, Houston, TX, USA.; Department of Chemistry, Rice University, Houston, TX, USA. |
| المصدر: | BioRxiv : the preprint server for biology [bioRxiv] 2024 Feb 07. Date of Electronic Publication: 2024 Feb 07. |
| نوع المنشور: | Preprint |
| اللغة: | English |
| بيانات الدورية: | Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet ISSN: 2692-8205 (Electronic) Linking ISSN: 26928205 NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| مستخلص: | Mesenchymal stem/stromal cells (MSCs) are an attractive platform for cell therapy due to their safety profile and unique ability to secrete broad arrays of immunomodulatory and regenerative molecules. Yet, MSCs are well known to require preconditioning or priming to boost their therapeutic efficacy. Current priming methods offer limited control over MSC activation, yield transient effects, and often induce expression of pro-inflammatory effectors that can potentiate immunogenicity. Here, we describe a 'genetic priming' method that can both selectively and sustainably boost MSC potency via the controlled expression of the inflammatory-stimulus-responsive transcription factor IRF1 (interferon response factor 1). MSCs engineered to hyper-express IRF1 recapitulate many core responses that are accessed by biochemical priming using the proinflammatory cytokine interferon-γ (IFNγ). This includes the upregulation of anti-inflammatory effector molecules and the potentiation of MSC capacities to suppress T cell activation. However, we show that IRF1-mediated genetic priming is much more persistent than biochemical priming and can circumvent IFNγ-dependent expression of immunogenic MHC class II molecules. Together, the ability to sustainably activate and selectively tailor MSC priming responses creates the possibility of programming MSC activation more comprehensively for therapeutic applications. Competing Interests: DECLARATION OF INTERESTS The authors declare no competing interests. |
| التعليقات: | Update in: Mol Ther Methods Clin Dev. 2024 Aug 08;32(3):101316. doi: 10.1016/j.omtm.2024.101316. (PMID: 39282077) |
| معلومات مُعتمدة: | R01 DK111599 United States DK NIDDK NIH HHS; R21 EB030772 United States EB NIBIB NIH HHS |
| فهرسة مساهمة: | Keywords: Mesenchymal stem cells; Signaling pathway engineering; immunosuppression; interferon gamma licensing; priming |
| تواريخ الأحداث: | Date Created: 20240219 Latest Revision: 20240924 |
| رمز التحديث: | 20240924 |
| مُعرف محوري في PubMed: | PMC10871228 |
| DOI: | 10.1101/2024.02.01.578489 |
| PMID: | 38370626 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2692-8205 |
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| DOI: | 10.1101/2024.02.01.578489 |