Optimized protocol for culturing menstrual blood-derived MSCs for combination with oncolytic adenoviruses in cancer
Marcel Costa-Garcia1, Laura Moya-Borrego1, Ramon Alemany Bonastre1
1Cancer Immunotherapy Group, Oncobell and iProCURE programs, IDIBELL-Institut Català d'Oncologia, 08907 L'Hospitalet de Llobregat, Barcelona, Spain.
Abstract:
Oncolytic viruses (OVs) are a promising therapeutic approach for cancer, although their systemic administration faces significant challenges. Mesenchymal stem cells have emerged as potential carriers to overcome these obstacles due to their tumor-tropic properties. This study investigates the use of menstrual blood-derived mesenchymal stem cells (MenSCs) as carriers for OVs in cancer therapy, focusing on enhancing their efficacy through different culture conditions. MenSCs were isolated from donors of different ages and cultured under normoxic and hypoxic conditions, with varying adherence capacities. Hypoxic conditions significantly improved MenSCs proliferation and tumor migration capabilities, as demonstrated by proliferation assays and RNA-sequencing analysis, which revealed upregulation of genes related to cell division and tumor tropism. In vivo studies using a lung adenocarcinoma mouse model confirmed that hypoxia-conditioned MenSCs had superior tumor-homing abilities. The study also demonstrated the feasibility of establishing a master and working cell bank from a single menstrual blood donation. These findings suggest that hypoxia-conditioned MenSCs could be highly effective as OV carriers, potentially leading to better clinical outcomes in cancer treatment by enhancing tumor targeting and therapeutic efficacy.
Insights
Menstrual blood stem cells (MenSCs) show promise as carriers for oncolytic viruses (OVs) in cancer therapy. Hypoxic preconditioning enhances MenSCs
Area of Science:
- Oncology
- Stem Cell Biology
- Virology
Background:
- Systemic administration of oncolytic viruses (OVs) for cancer therapy faces challenges.
- Mesenchymal stem cells (MSCs) possess tumor-tropic properties, making them suitable carriers.
- Menstrual blood-derived MSCs (MenSCs) offer a potential source for cell-based therapies.
Purpose of the Study:
- To investigate MenSCs as carriers for OVs in cancer treatment.
- To enhance MenSC efficacy as OV carriers through optimized culture conditions.
- To evaluate the impact of hypoxia on MenSC proliferation, tumor tropism, and cell banking.
Main Methods:
- Isolation and culture of MenSCs from donors of varying ages.
- Culturing MenSCs under normoxic and hypoxic conditions.
- Assessment of MenSC proliferation, tumor migration (in vitro and in vivo), and gene expression (RNA-sequencing).
- Feasibility assessment of establishing master and working cell banks from menstrual blood.
Main Results:
- Hypoxic conditions significantly enhanced MenSC proliferation and tumor migration capabilities.
- RNA-sequencing revealed upregulation of cell division and tumor tropism genes under hypoxia.
- In vivo studies confirmed superior tumor-homing abilities of hypoxia-conditioned MenSCs in a lung adenocarcinoma model.
- Successful establishment of MenSC master and working cell banks from a single donation was demonstrated.
Conclusions:
- Hypoxia-conditioned MenSCs are effective carriers for oncolytic viruses.
- Enhanced tumor targeting and therapeutic efficacy are achievable with hypoxia-conditioned MenSCs.
- MenSCs derived from menstrual blood offer a viable and scalable cell source for OV delivery.
