Exosomes (EVs) are known to mediate many of the therapeutic effects of stem cells. Currently, EVs have to be purified from cell culture conditioned media using tedious, costly and time-consuming protocols that are difficult to perform under Good Manufacturing Practices (GMP) conditions. The Cell-in-a-Box encapsulation technology allows efficient enrichment of EVs at high concentration since they are released from the encapsulated cells via the semipermeable pores, which selectively enable the release of small particles but not of the mesenchymal stem cells (MSCs). Moreover, Cell-in-a-Box provides 3D culture conditions for the MSCs. The technology can be used in cell culture allowing GMP production. Alternatively, the encapsulated cells can be implanted into patients as a retrievable delivery device that shields the cells from clearance, whilst they continuously produce EVs, growth factors, hormones and other small therapeutically relevant molecules. Moreover, the EVs produced after encapsulation can themselves be used as drug-loaded delivery vehicles. This technology will be invaluable for the treatment of regenerative diseases and Inflammatory disease.
To demonstrate the use of Cell-in-a-Box, we have encapsulated menstrual MSCs and purified EVs from the cell culture medium.
The isolated EV express CD9, CD63 and CD81 and retained the expected biological activities of MSCs such as pro-angiogenic effect, neuritic outgrowth stimulation in hippocampal neurons and immunosuppression of T cells in vitro.