P080
Optimized protocol of menstrual blood-derived mesenchymal stem cell isolation and amplification to combine with oncolytic adenovirus for cancer treatment
L Moya-Borrego(1) M Costa-García(1) R Alemany(1) R Moreno(1)
1:IDIBELL-ICO
The use of oncolytic viruses (OVs) as candidates in combination with cancer immunotherapies has gained interest for transforming "cold" into "hot" tumours, where immunotherapies are most effective. However, successful systemic administration of OVs is limited by several challenges, which can be overcome by using mesenchymal stem cells (MSCs) as OV-cell carriers due to their natural tumour tropism and immunomodulatory properties. In our previous work, we presented menstrual blood as a new, less invasive, and cheaper source for obtaining MSCs. We demonstrated that in comparison to classical bone marrow-derived MSCs (BM-MSCs), menstrual blood-derived MSCs (MenSCs) can be easily isolated without invasive methods, have an increased proliferation rate, and can be efficiently infected with oncolytic adenoviruses (OAds), leading to similar viral replication and release. Furthermore, we pointed out the MenSCs tumour-homing properties and immunostimulatory potential when infected with OAds. In this work, we present an improved protocol to isolate and amplify MenSCs to combine with OAds. We have evaluated the impact of donor age and culture conditions on MenSCs' growth potential, specific transcriptional profile, and viral production. Our findings indicate that MenSCs grown under hypoxic conditions have higher proliferation potential and enhanced tumour targeting profile. Moreover, MenSCs obtained from a single donor during one menstrual cycle can be expanded to more than 10⁹ cells, which would cover the hypothetical needs of a Phase I trial, eliminating the variability associated with cell heterogenic origin when using BM-MSCs. Altogether, our results suggest MenSCs could be a promising platform for delivering OVs to tumours.
