ArticleStem cell research & therapy2026
Donor age and sex program MSC secretome signaling: a quadrant framework for precision therapy.
Article in Stem cell research & therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundClinical responses to mesenchymal stromal cell (MSC) therapies remain variable because MSCs are often treated as uniform biologics despite donor-programmed differences. Evidence indicates that developmental maturity (fetal vs. adult) and biological sex (female vs. male) bias the MSC secretome and downstream signalling (NF-κB, PI3K/AKT-ERK, TGF-β/Smad, Wnt/β-catenin), potentially shaping anti-inflammatory, angiogenic, anti-fibrotic, and regenerative functions.
methodsWe conducted a targeted synthesis of peer-reviewed in vitro, preclinical, and early clinical studies that relate donor features (maturity, sex) to secretome mediators (EV miRNAs/proteins; cytokines/growth factors) and pathway readouts. Findings were organized along mediator→pathway→function chains and distilled into a rule-based quadrant model (fetal♀, fetal♂, adult♀, adult♂), with qualitative consideration of tissue source and manufacturing variables.
resultsConsistent donor-programmed skews emerged: fetal female MSCs enrich IL-10/TSG-6 and miR-125a with NF-κB suppression and Treg/DC-tolerizing activity; fetal male MSCs elevate VEGF/bFGF/HGF with PI3K/AKT-ERK activation supporting angiogenic survival; adult female MSCs show TGF-β/Smad tuning compatible with anti-fibrotic remodelling; adult male MSCs upregulate WNT5A/IGF-1/Runx2, favouring regenerative/osteogenic programmes with comparatively lower oxidative-stress resilience. We translate these patterns into fit-for-purpose potency/CQA panels (e.g., IL-10/TSG-6; VEGF/HGF with pAKT/pERK; TGF-β/Smad; WNT5A/IGF-1/Runx2) and concise trial schemas (stratification by maturity×sex; pathway-anchored pharmacodynamic biomarkers).
conclusionsA signaling-centered, donor-stratified framework may help organize heterogeneous findings in the MSC field and generate testable predictions for potency assessment, indication matching, and study design. Because most available evidence evaluates sex or maturity in isolation and under diverse tissue sources and manufacturing conditions, the proposed quadrant model should be interpreted as hypothesis-generating. Prospective, harmonized, head-to-head validation across donor quadrants will be required to determine its translational utility.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.