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.
Human adipose-derived stem cells (ASCs) show immense promise for treating inflammatory diseases, attributed primarily to their potent paracrine signaling. Previous investigations demonstrated that short-term Rapamycin preconditioning of bone marrow-derived stem cells (BMSCs) elevated secretion of prostaglandin E2, a pleiotropic molecule with therapeutic effects in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS), and enhanced immunosuppressive capacity in vitro. However, this has yet to be examined in ASCs. The present study examined the therapeutic potential of short-term Rapamycin-preconditioned ASCs in the EAE model. Animals were treated at peak disease with control ASCs (EAE-ASCs), Rapa-preconditioned ASCs (EAE-Rapa-ASCs), or vehicle control (EAE). Results show that EAE-ASCs improved clinical disease scores and elevated intact myelin compared to both EAE and EAE-Rapa-ASC animals. These results correlated with augmented CD4+ T helper (Th) and T regulatory (Treg) cell populations in the spinal cord, and increased gene expression of interleukin-10 (IL-10), an anti-inflammatory cytokine. Conversely, EAE-Rapa-ASC mice showed no improvement in clinical disease scores, reduced myelin levels, and significantly less Th and Treg cells in the spinal cord. These findings suggest that short-term Rapamycin preconditioning reduces the therapeutic efficacy of ASCs when applied to late-stage EAE.
Objectives
Head and neck cancer (HNC) patients experience greater financial toxicity than other cancer patients. Research on financial toxicity has concentrated on patients despite many informal caregivers sharing finances and reducing work hours to provide patient care. Thus, our pilot study: (1) assessed the feasibility of financial toxicity screening of HNC patients and their caregivers, and (2) described financial toxicity levels of HNC patients and their caregivers.
Methods
We surveyed English‐speaking adult HNC patients initiating treatment at a National Cancer Institute‐designated Comprehensive Cancer Center and their informal caregivers. This survey assessed demographics and financial toxicity through the Comprehensive Score for Financial Toxicity (COST) measure (0–44 range; lower score indicates higher financial toxicity). Screening feasibility was defined as ≥50% consent rate and ≥60% data completion rate.
Results
Our sample included 27 HNC patients and 9 caregivers. They both had slightly lower consent and completion rates than our goals. Patients reported a median COST score of 27 while caregivers reported a median COST score of 16. Approximately 25.9% of patients and 44.4% of caregivers reported high financial toxicity (COST < 17.5). Caregivers reported high concerns about their future financial health and their ability to control the amount of their financial contributions to the patient's care.
Conclusions
Patients and caregivers may require additional outreach approaches beyond emailed questionnaires to screen for their financial toxicity systematically. Future research is needed to replicate our results to determine whether differences in financial toxicity occur between patients and caregivers and identify areas of focus for interventions.
Level of evidence
IV.
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