Mesenchymal stem cell secretome and exosomes as potential advanced therapy medicinal products for treating a failing heart

Table 4 Head-to-head comparison of mesenchymal stem cell-based therapy, mesenchymal stem cell-derived exosome-based therapy, and mesenchymal stem cell-derived secretome-based therapy approaches

Parameter	MSC therapy	MSC-derived secretome	MSC-derived exosomes
Composition	Live cells can secrete various bioactive factors	A cell-free mixture containing soluble proteins, cytokines, chemokines, nucleic acids, and small extracellular vesicles released by MSCs	Nanosized vesicles (30-150 nm) enriched with proteins, lipids, and regulatory RNAs (miRNAs) that reflect the molecular profile of their parent MSCs
Isolation and production	Obtained from donor tissue (bone marrow, adipose tissue, or umbilical cord) and expanded under GMP conditions	Produced by culturing MSCs and collecting the conditioned medium, in addition to centrifugation and filtration to remove cells	Generated through further purification of the secretome using ultracentrifugation, filtration, or chromatography
Storage and stability	Requires cryopreservation (-196 °C).	Can be stored frozen (-20 °C to -80 °C) or lyophilized	Similar storage profile to the secretome; stable under freezing or lyophilized conditions
Dosing units	Defined by viable cell number [e.g., (10-100) × 106 cells per dose]	Quantified by total protein concentration or biological activity (e.g., mg of secreted protein)	Expressed by vesicle count (e.g., 1010 particles) or total exosomal protein content (μg)
Mechanism of action	Primarily functions through paracrine signaling, releasing bioactive factors over time and supporting differentiation into cardiac or vascular cells	Acts exclusively through soluble paracrine mediators that promote tissue repair via anti-inflammatory, angiogenic, and regenerative signaling pathways	Delivers specific molecular cargo (miRNAs, proteins, lipids) into target cells, modulating gene expression and promoting tissue regeneration; can be bioengineered for targeted therapeutic effects
Manufacturing complexity	High: Requires GMP-level cell culture, cell banking, karyotype and sterility testing, and cryostorage logistics	Moderate: Requires MSC culture, conditioned medium collection, and downstream processing (e.g., filtration and concentration)	High: Includes all steps of secretome production, specialized purification, and molecular profiling
Scalability	Limited by donor cell proliferation and donor variability. Large-scale expansion increases cost and heterogeneity	Highly scalable; one MSC source can produce large volumes of secretome using culture systems with minimal donor dependence	Partially scalable - while MSC culture is scalable, large-scale exosome isolation and purification remain technically demanding
Cost implications	High production cost due to cell culture, quality control, and cryogenic storage	Lower cost; major expenses arise from culture media and concentration processes, but no live-cell storage is required	Moderate to high cost due to intensive purification techniques

MSC: Mesenchymal stem cell; GMP: Good Manufacturing Practice; miRNAs: MicroRNAs.