Stem cell derived exosomes: Emerging cell-free therapeutics for neurodegenerative disorders

Table 1 Components of exosomes structure

Serial number	Structure	Compositions	Functions
1	Cytoskeletal elements	Actin, tubulin, cofilin, talin, vimentin	Structural support, vesicle formation, transport
2	Lysosomal protein	Lamp2b	Degradation, protein sorting, membrane trafficking
3	Exosome membrane	Sphingomyelin, phosphatidylserine, cholesterol, and ceramides	Encloses exosomal content, interacts with target cells
4	Tetraspanin family	CD63, CD9, CD37, CD81, and CD82	Membrane organization, protein interactions, cell adhesion
5	HSPs	HSP70, HSP90, HSP20, HSP27, HSP60, HSC70	Protein folding, stress response, cell protection
6	Intercellular adhesion molecule	ICAM-1, integrins, p-selectin, lactadhesion	Cell-cell interactions, signaling, immune responses
7	Fusion and membrane transport proteins	GTPases, flotillin, annexins, Rabs, dynamin, syntaxin	Vesicle fusion, content release, membrane trafficking
8	Transmembrane proteins	CD13, LAM1/2, PGRL	Signaling, cell-cell interactions, membrane anchoring
9	Immuno-regulator molecules	CD80, CD86	Modulate immune responses, tolerance, inflammation
10	Antigen presentation	MHC class I and II molecules	Activate immune cells, antigen display
11	Nucleic acids	mRNA, DNA, and non-coding RNAs	Genetic information transfer, gene regulation
12	Enzymes	Glycosidases, GAPDH, nitric oxide synthase, catalase, phosphatases, lipases, pgk1, ATPase	Catalyze biochemical reactions, metabolic processes
13	Growth factors and cytokines	TRAIL, TNF-α, TGF-β	Cell growth, differentiation, signaling
14	ESCRT-dependent exosomal biogenesis	ALIX, TSG101, clathrin	Exosome formation, sorting, release

Lamp: Lysosomal associated membrane protein; CD: Cluster of differentiation; HSP: Heat shock proteins; HSC70: Heat shock cognate protein 70; ICAM: Intercellular adhesion molecule; MHC: Major histocompatibility complex; GAPDH: Glyceraldehyde-3-phosphate dehydrogenase; pgk1: Phosphoglycerate kinase 1; TRAIL: Tumor necrosis factor-related apoptosis-inducing ligand; TNF-α: Tumor necrosis factor α; TGF-β: Transforming growth factor β; ALIX: Apoptosis-linked gene 2-interacting protein X; TSG101: Tumor susceptibility gene 101.

Table 2 Neuroregenerative effects of exosomes

Mechanisms	Functions	Effects
Neurotransmitter release	Exosomes release neurotransmitters, promoting neuronal communication	Enhanced synaptic plasticity, cell survival
Cellular communication	Exosomes facilitate communication between neurons, oligodendrocytes, and microglia	Regulation of cellular processes, neuroprotection
Epigenetic control	Exosomes influence gene expression, regulating neurogenesis and neuroinflammation	Modulation of neuroregenerative processes
Synaptic plasticity	Exosomes promote synaptic strengthening, neuronal adaptation	Improved cognitive function, memory
Neuroprotection	Exosomes transfer protective signals, enhancing cell survival	Reduced neuroinflammation, oxidative stress
Calcium influx regulation	Exosomes modulate calcium influx, regulating neuronal excitability	Maintenance of neuronal homeostasis
Serotonin-mediated release	Exosomes released via serotonin pathways, influencing mood regulation	Modulation of mood, cognitive function
Microglia activation	Exosomes from microglia regulate neuroinflammation, immune responses	Neuroprotection, reduced inflammation
Oligodendrocyte support	Enhance neuronal survival, myelination	Improved neuronal regeneration
Blood-brain barrier crossing	Facilitate neuroregeneration	Access to central nervous system for therapeutic interventions

Table 3 Comparison of exosomes isolation methods

Isolation method	Purity	Pros	Cons
Ultracentrifugation	Low	Widely used, simple protocol	Time-consuming, multi-step process, high contamination risk
Size exclusion chromatography	High	Fast, simple and low-cost	Subtyping involves significant sample sizes and another procedure
Immunoaffinity-based approaches	High	Does not require special equipment, enrich cell-specific exosomes by targeted surface markers	Relies on high-cost antibodies, time consuming
Polymer-based precipitation	Low-to-medium	Low-cost method, easy protocol	Contamination risk, high cost, time consuming
Microfluidic devices	Low	Does not require special equipment, cost-effective	Design complexity
Nanotechnology	High	Commercially obtainable nanowires	High cost, restricts sample size