Abstract
The therapeutic potential of mesenchymal stem cell (MSC) extracellular vesicles (EV) is currently under investigation in many pathological contexts. Both adult and perinatal MSC are being considered as sources of EV. Herein, we address antigen expression of cord blood and bone marrow MSC and released EV to define an identity and quality parameter of MSC EV as a medicinal product in the context of clinical applications. The research focuses on EV-shuttled neural/glial antigen 2 (NG2), which has previously been detected as a promising surface marker to distinguish perinatal versus adult MSC. Indeed, NG2 was significantly more abundant in cord blood than bone marrow MSC and MSC EV. Ultracentrifuge-isolated EV were then challenged for their pro-angiogenic properties on an xCELLigence system as quality control. NG2+ cord blood MSC EV, but not bone marrow MSC EV, promote bFGF and PDGF-AA proliferative effect on endothelial cells. Likewise, they successfully rescue angiostatin-induced endothelial cell growth arrest. In both cases, the effects are NG2-dependent. These results point at NG2 as an identity and quality parameter for cord blood MSC EV, paving the way for their clinical translation.
Highlights
In the last few years, a remarkable shift in the mesenchymal stem cell (MSC) field has occurred [1].The focus of the researchers has switched from the differentiation and growth factor-secreting properties of MSC to the therapeutic potential of their extracellular vesicles (EV) [2]
The expression of neural/glial antigen 2 (NG2) was addressed in long-living cord blood mesenchymal stem cells (LL-cbMSC) and bone marrow MSC as representative of perinatal and adult MSC populations, respectively
Clinical translation of innovative advanced therapy medicinal products (ATMP) entails a great effort dedicated to dealing with cellular derivatives as a proper pharmaceutical
Summary
The focus of the researchers has switched from the differentiation and growth factor-secreting properties of MSC to the therapeutic potential of their extracellular vesicles (EV) [2] This term was adopted by the International Society for Extracellular Vesicles (ISEV) [3,4] to comprise the different class of membranous vesicles secreted by virtually all cell types into the extracellular environment. Translation to the clinical application of vesicular therapies entails the definition of clinical-grade identity parameters and the development of rapid and simple assays indicative of retention of biological activity after production and storage. These tests will be needed to guarantee the
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