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Clinical outcome is unlinked to injection of adipose-derived regenerative cells in the axilla of breast cancer-related lymphedema patients

ABSTRACT: Background: Injection of autologous adipose-derived regenerative cells (ADRCs) combined with lipotransfer has been suggested to alleviate symptoms in diseases including breast cancer-related lymphedema (BCRL). We recently performed a randomized controlled trial injecting lipoaspirate with ADRCs into the axilla of BCRL patients, and here we aimed in the intervention group to define in an unbiased fashion whether ADRC injection was linked to the clinical outcome. Results: Unbiased multifactorial analysis ranked and defined the clinical outcomes (Sf36 physical change, L-Dex Lymph Change, ICG mdanderson change) with the highest effect on BRCL patients. The 10 patients with the highest- and lowest effect (five responders and five non-responders) were included in the study. No difference between non-responders and responders were observed for injected ADRC number/size/viability (p>0.05). In scRNAseq, we did not find any major difference (p>0.05) between groups in ADRC composition regarding adipose derived stem cells, endothelial-, smooth muscle-, T-, B-, mast cells as well as macrophages, which was verified by flow cytometry. Differential subcluster gene expression between groups were for 92.5% of genes below the threshold of 1.5, and thus neglible. Together this suggested that the ADRC phenotype was indistinguishable between BRCL responders and non-responders to the intervention.

ORGANISM(S): Homo sapiens

PROVIDER: GSE276533 | GEO | 2024/11/20

REPOSITORIES: GEO

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Project description:Objectives: We monitored the mRNA expression profiles of peripheral blood cells during treatment with a tumor necrosis factor-a inhibitor, infliximab, in patients with rheumatoid arthritis (RA). Using a DNA microarray analysis, we demonstrated a unique set of genes, with distinct baseline and post-treatment changes in expression between responders and non-responders to infliximab treatment.Methods: Using a customized low-density cDNA microarray and a reliable data collection system, we monitored the mRNA expression profiles of whole blood cells from 18 RA patients before and after the infusion of infliximab for up to 22 weeks. The clinical response to treatment with infliximab was determined using the American College of Rheumatology (ACR) response criteria, the disease activity score of 28 joints (DAS28), and individual clinical parameters. The patients were classified as responders or non-responders based on their ACR50% response at 22 weeks. Results: Approximately 15% of the total genes were found to exhibit a greater than 1.5-fold change, compared to their reference values, at one or more time points during the 22 weeks of infliximab therapy. The expression of inflammatory genes, such as interferon-related genes, was strongly correlated with the serum level of C-reactive protein and the DAS28. The increased expression of inflammatory genes in responders was normalized within 2 weeks and then remained at a normal level during the treatment period. In contrast, in the non-responders, the elevated expression at baseline, although it was significantly decreased at 2 weeks, returned to the baseline level after 14 weeks. In addition to inflammatory genes, we identified several groups of genes with distinct differences in expression between the responders and non-responders.Conclusions: Our results suggest that a customized low-density microarray is useful for monitoring mRNA expression profiles in peripheral blood cells, enabling us to identify a unique set of genes with differentially regulated expressions in responders and non-responders to a TNF inhibitor among patients with RA. Keywords: disease state analysis 18 RA Patients, We have collected blood samples into PAXgene tube systems for microarray measurement from patients as follows, just before first iv-injection of infliximab, 2 weeks, 14 weeks, and 22 weeks after first infliximab injection.

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Clinical outcome is unlinked to injection of adipose-derived regenerative cells in the axilla of breast cancer-related lymphedema patients

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