Pilot intraindividual secretome profiling of adipose-derived stem cells in multiple symmetric lipomatosis
Abstract
Multiple symmetric lipomatosis (MSL) is a rare adipose tissue disease characterized by progressive, non-encapsulated, symmetrical fat accumulation. Its pathophysiology is still not completely understood. Here, we performed the first intraindividual comparison of secretomes of human adipose-derived stem cells (hASCs) isolated from affected and unaffected regions of n = 15 patients (proteomic discovery cohort n = 5). Affected MSL-hASCs tend to show accelerated metabolic signals and higher cell densities with preserved adipogenic differentiation capacity. Secretome transfer of affected MSL-hASCs significantly increased metabolic activity of wt-hASCs after 24 h in 4/7 samples (all explorative Benjamini-Hochberg corrected p = 0.040). Bottom-up proteomic analysis identified 811 proteins, of which 220 were classified as secreted. Thirteen proteins exhibited nominally significant dysregulation of expression, including CALR ( p = 0.0061), LAMC1 ( p = 0.0241), S100A7 ( p = 0.0281) and HDGF ( p = 0.0474), but none remained significant after application of the Benjamini-Hochberg (BH) correction to control the False Discovery Rate (FDR) at 0.05. Transcriptional validation by rt-qPCR revealed a trend toward downregulation of hLAMA4 and hCFB (both p = 0.0625). In conclusion, convergent patterns are consistent with extracellular matrix remodeling and PI3K/AKT-ERK-associated proliferative signaling. This model supports a hypothesis of progenitor-level dysregulation rather than a single clonal driver in MSL, which will require further mechanistic validation in larger cohorts.
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BibTeX
@article{reinhard2026pilot,
title = {{Pilot intraindividual secretome profiling of adipose-derived stem cells in multiple symmetric lipomatosis}},
author = {Ruben Reinhard and Oliver Felthaus and Andreas Siegmund and Katharina Limm and Peter J. Oefner and Marc Ruewe and Silvan Eisenmann and Christian Festbaum and Lukas Prantl and Dmytro Oliinyk},
journal = {Scientific Reports},
year = {2026},
month = oct,
doi = {10.1038/s41598-026-74618-w},
url = {https://www.nature.com/articles/s41598-026-74618-w},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Pilot intraindividual secretome profiling of adipose-derived stem cells in multiple symmetric lipomatosis
AU - Ruben Reinhard
AU - Oliver Felthaus
AU - Andreas Siegmund
AU - Katharina Limm
AU - Peter J. Oefner
AU - Marc Ruewe
AU - Silvan Eisenmann
AU - Christian Festbaum
AU - Lukas Prantl
AU - Dmytro Oliinyk
PY - 2026
DA - 2026/10/10
JO - Scientific Reports
DO - 10.1038/s41598-026-74618-w
UR - https://www.nature.com/articles/s41598-026-74618-w
AB - Multiple symmetric lipomatosis (MSL) is a rare adipose tissue disease characterized by progressive, non-encapsulated, symmetrical fat accumulation. Its pathophysiology is still not completely understood. Here, we performed the first intraindividual comparison of secretomes of human adipose-derived stem cells (hASCs) isolated from affected and unaffected regions of n = 15 patients (proteomic discovery cohort n = 5). Affected MSL-hASCs tend to show accelerated metabolic signals and higher cell densities with preserved adipogenic differentiation capacity. Secretome transfer of affected MSL-hASCs significantly increased metabolic activity of wt-hASCs after 24 h in 4/7 samples (all explorative Benjamini-Hochberg corrected p = 0.040). Bottom-up proteomic analysis identified 811 proteins, of which 220 were classified as secreted. Thirteen proteins exhibited nominally significant dysregulation of expression, including CALR ( p = 0.0061), LAMC1 ( p = 0.0241), S100A7 ( p = 0.0281) and HDGF ( p = 0.0474), but none remained significant after application of the Benjamini-Hochberg (BH) correction to control the False Discovery Rate (FDR) at 0.05. Transcriptional validation by rt-qPCR revealed a trend toward downregulation of hLAMA4 and hCFB (both p = 0.0625). In conclusion, convergent patterns are consistent with extracellular matrix remodeling and PI3K/AKT-ERK-associated proliferative signaling. This model supports a hypothesis of progenitor-level dysregulation rather than a single clonal driver in MSL, which will require further mechanistic validation in larger cohorts.
SN - 2045-2322
ER -