Methods for culturing mesenchymal stem cells, compositions and implementations thereof

A method of generating a population of primed mesenchymal stem cell-derived exosomes, the method comprising:

• (a) expanding a population of mesenchymal stem cells (MSCs) in culture;
• (b) contacting the population of MSCs with a cell-derived conditioned medium derived from a population of cells different from the population of MSCs, and contacting the population of MSCs with at least one defined priming agent, to obtain a population of primed MSCs;
• (c) growing the population of the primed MCSs in culture to produce a primed MSC-derived conditioned medium;
• (d) collecting the primed MSC-conditioned medium;
• and
• (e) purifying the exosomes from the primed MSC-conditioned medium.

A population of primed MSC-derived exosomes that are characterized by having, compared to unprimed MSC-derived exosomes:

• (a) at least 2× higher expression level of sFLT1;
• (b) an expression level of vascular endothelial growth factor (VEGF) that is a quarter or less of the expression in unprimed MSC-derived exosomes;
• (c) at least 2× higher expression level of hepatic growth factor (HGF);
• and
• (d) at least 3× higher expression level of nerve growth factor (NGF).

A method of generating a population of primed mesenchymal stem cell-derived exosomes, the method comprising:

• (a) culturing a population of mesenchymal stem cells (MSCs) in a culture medium;
• (b) contacting the population of MSCs with an nuclear factor erythroid 2-related factor 2 (Nrt2) activator to obtain a population of primed MSCs;
• (c) growing the population of the primed MCSs in a collection medium, wherein the collection medium becomes enriched with exosomes produced by the primed MSCs, thereby producing a primed-MSC-derived conditioned medium;
• (d) collecting the primed MSC-conditioned medium;
• and
• (e) purifying the exosomes from the primed MSC-conditioned medium.