Case Study | May 28, 2026
Multi-Omics Exosome Profiling Reveals Potential Targets for Attenuating Diabetic Inflammatory Pathophysiology
Sapient contributes multi-omic exosome analysis – including proteomics, metabolomics, and lipidomics – to a study by GATC Health identifying distinct multi-omic signatures in stem cell–derived exosomes that may protect insulin-producing cells from damage in diabetes.
Mesenchymal stem cell (MSC)-derived exosomes are emerging as a promising cell-free therapeutic approach for diabetes, capable of modulating inflammatory and metabolic processes as well as tissue regeneration. However, a critical challenge in the development of MSC-based therapies is the effects of repeated in-vitro expansion.
As MSCs undergo successive cell culture passages, they undergo cellular senescence and begin secreting pro-inflammatory factors rather than regenerative ones. Therefore, exosomes from late-passage or older MSCs have diminished or even counterproductive therapeutic efficacy. Understanding how passage stage influences exosomal content is essential for developing effective, reproducible exosome-based interventions.
This study, led by GATC Health, sought to comprehensively characterize the molecular cargo of exosomes derived from early- and late-passage bone marrow and umbilical cord MSCs using Sapient’s mass spectrometry-based workflows for discovery proteomics, metabolomics, and lipidomics.
The multi-omic exosome analysis identified a distinct anti-inflammatory and cytoprotective molecular signature in early-passage mesenchymal stem cell exosomes with potential relevance for diabetes therapy.
To profile the molecular cargo of exosomes derived from early-passage (passages 2–5) and late-passage (passage >10) bone marrow and umbilical cord MSCs, the study employed three complementary Sapient mass spectrometry (MS) platforms, each generating a detailed molecular layer of the exosomal landscape.
For proteomics analysis, exosomes were lysed and analyzed via MS with proprietary algorithms for enhanced separation, identification, and quantification of exosomal protein contents. Exosomal metabolites were extracted and profiled using Sapient’s rLC-MS systems which enable simultaneous detection of over 15,000 small molecule biomarkers per sample. Lipid content was also profiled using rLC-MS, capturing thousands of lipid species across various classes including glycerophospholipids, sphingolipids, sterol esters, cardiolipins, and FAHFAs.
Experimental workflow with multi-omics profiling. Figure reproduced from Lakey et. al., “Multi-Omic Characterization of MSC-Derived Exosomes and Conditioned Media Reveals Passage-Dependent Shifts with Therapeutic Implications for Diabetes”
Integrated Multi-Omics Factor Analysis (MOFA) was then applied to identify latent factors driving molecular variation across all three omics layers, and pathway enrichment analyses were performed against publicly available diabetes-related gene expression and metabolite datasets.
Key Study Findings
Multi-Omics Factor 1 was identified as the principal source of variation, clearly distinguishing early- from late-passage exosomes across the proteome, metabolome, and lipidome.
- Early-passage exosomes carried a distinct anti-inflammatory, cytoprotective signature enriched in heat-shock proteins and antioxidant enzymes – molecules that may counteract β-cell apoptosis and oxidative stress in diabetes.
- Late-passage conditioned media exhibited a pro-inflammatory Senescence-Associated Secretory Phenotype (SASP), marked by increased expression of inflammatory mediators and disrupted metabolic homeostasis.
- Pathway enrichment analyses against publicly available Type 1 Diabetes (T1D) transcriptomic and metabolomic datasets revealed that early-passage exosomes shared latent factors inversely correlated with diabetes-related gene signatures — indicating these vesicles could help restore immune and metabolic homeostasis disrupted in T1D.
These findings demonstrate that MSC passage stage critically influences exosomal content and function, and that integrated multi-omics profiling can distinguish between regenerative and inflammatory vesicle populations at a molecular level. Additionally, early-passage MSC-derived exosomes exhibit potent anti-inflammatory and cytoprotective molecules that may mitigate ß-cell injury, immune dysregulation, and metabolic dysfunction in diabetes.
Explore more of the study data here.