| Autor: |
Wise RM; Neuroscience Program, Tulane Brain Institute, Tulane University School of Science & Engineering, New Orleans, LA 70118, USA.; Center for Stem Cell Research & Regenerative Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA., Al-Ghadban S; Center for Stem Cell Research & Regenerative Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA.; Department of Microbiology, Immunology and Genetics, University of North Texas Health Science Center, Fort Worth, TX 76107, USA., Harrison MAA; Neuroscience Program, Tulane Brain Institute, Tulane University School of Science & Engineering, New Orleans, LA 70118, USA.; Center for Stem Cell Research & Regenerative Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA., Sullivan BN; Neuroscience Program, Tulane Brain Institute, Tulane University School of Science & Engineering, New Orleans, LA 70118, USA.; Center for Stem Cell Research & Regenerative Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA., Monaco ER; Neuroscience Program, Tulane Brain Institute, Tulane University School of Science & Engineering, New Orleans, LA 70118, USA., Aleman SJ; Neuroscience Program, Tulane Brain Institute, Tulane University School of Science & Engineering, New Orleans, LA 70118, USA., Donato UM; Neuroscience Program, Tulane Brain Institute, Tulane University School of Science & Engineering, New Orleans, LA 70118, USA., Bunnell BA; Center for Stem Cell Research & Regenerative Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA.; Department of Microbiology, Immunology and Genetics, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.; Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112, USA. |
| Abstrakt: |
Human adipose-derived stem cells (hASCs) are potent modulators of inflammation and promising candidates for the treatment of inflammatory and autoimmune diseases. Strategies to improve hASC survival and immunoregulation are active areas of investigation. Autophagy, a homeostatic and stress-induced degradative pathway, plays a crucial role in hASC paracrine signaling-a primary mechanism of therapeutic action. Therefore, induction of autophagy with rapamycin (Rapa), or inhibition with 3-methyladenine (3-MA), was examined as a preconditioning strategy to enhance therapeutic efficacy. Following preconditioning, both Rapa and 3-MA-treated hASCs demonstrated preservation of stemness, as well as upregulated transcription of cyclooxygenase-2 (COX2) and interleukin-6 (IL-6). Rapa-ASCs further upregulated TNFα-stimulated gene-6 (TSG-6) and interleukin-1 beta (IL-1β), indicating additional enhancement of immunomodulatory potential. Preconditioned cells were then stimulated with the inflammatory cytokine interferon-gamma (IFNγ) and assessed for immunomodulatory factor production. Rapa-pretreated cells, but not 3-MA-pretreated cells, further amplified COX2 and IL-6 transcripts following IFNγ exposure, and both groups upregulated secretion of prostaglandin-E2 (PGE2), the enzymatic product of COX2. These findings suggest that a 4-h Rapa preconditioning strategy may bestow the greatest improvement to hASC expression of cytokines known to promote tissue repair and regeneration and may hold promise for augmenting the therapeutic potential of hASCs for inflammation-driven pathological conditions. |
