5'-nucleotidase (CD73) on mesenchymal stem cell-derived extracellular vesicles (CD73-MSC-EV)

5'-nucleotidase (CD73) is a glycosylphosphatidylinositol (GPI)-anchored cell surface enzyme that plays a pivotal role in the purinergic signaling pathway by catalyzing the conversion of extracellular adenosine monophosphate (AMP) to adenosine [1, 2]. When localized on or within mesenchymal stem cell-derived extracellular vesicles (MSC-EVs), CD73 acts as a primary mediator of the immunomodulatory and regenerative properties of these cell-free therapeutic agents [3]. The enzymatic activity of CD73 on the EV surface facilitates the production of adenosine, which binds to P1 receptors (specifically A2A and A2B) on target cells to suppress pro-inflammatory cytokine production and promote an M2-like anti-inflammatory macrophage phenotype [4, 5]. This mechanism has been extensively studied in the context of myocardial ischemia-reperfusion injury, where MSC-EV-associated CD73 significantly reduces infarct size and promotes cardiac repair [3, 6]. While CD73 is a prominent target for monoclonal antibodies and small molecule inhibitors in oncology to prevent adenosine-mediated immune evasion, its presence on MSC-EVs is leveraged for therapeutic benefit in inflammatory and ischemic diseases [7, 8]. The characterization of CD73 activity is often used as a potency assay for MSC-EV products, making it a critical biomarker for manufacturing and efficacy monitoring [9]. Sources: [1] UniProt P21589; [2] Zimmermann H. (1992) Biochem J; [3] Lai RC, et al. (2010) Stem Cell Res; [4] Antonioli L, et al. (2013) Nat Rev Cancer; [5] Zhang S, et al. (2016) Osteoarthritis Cartilage; [6] Arslan F, et al. (2013) Stem Cell Res; [7] Bongiovanni L, et al. (2021) Front Immunol; [8] Arcus Biosciences Pipeline; [9] Willis GR, et al. (2017) Stem Cells Transl Med.

Other names

NT5EEcto-5'-nucleotidase5'-NTMSC-derived exosomal CD73CD73-positive MSC-EVs

Hydrolysis of extracellular adenosine monophosphate (AMP) to adenosine, which subsequently activates P1 receptors (A2A and A2B) to modulate immune cell activity and promote tissue regeneration.