Expression of ABCB1, ABCC1, and LRP in Mesenchymal Stem Cells from Human Amniotic Fluid and Bone Marrow in Culture—Effects of In Vitro Osteogenic and Adipogenic Differentiation
Mesenchymal stem cells (MSCs) are multipotent cells with the potential to differentiate into various lineages. They have also the potential to protect themselves against harmful stimuli to maintain their functional integrity. Drug resistance-related transporters such as ABCB1 (P-glycoprotein; P-gp), ABCC1 (MRP1; multidrug resistance-related Protein 1), and LRP (lung resistance protein) may protect MSCs against toxic substances such as chemotherapeutic agents. This study evaluated ABCB1, ABCC1, and LRP before and after the differentiation of MSCs derived from human amniotic fluid (AF) and bone marrow (BM). P-gp expression in both AFMSCs and BMMSCs was analyzed by immunocytochemistry, and pump function was analyzed by cell viability assay with doxorubicin (DOX) and Rhodamine 123 (Rh 123) dye exclusion. ABCB1, ABCC1, and LRP gene expression was determined by RT-PCR both before and after osteogenic and adipogenic differentiation. The MES-SA/DX5 cell line was used as a model of resistance to DOX and the overexpression of P-gp. Both AFMSCs and BMMSCs displayed a high P-gp expression, although lower than MES-SA/DX5 control cells. It was shown that both, undifferentiated AFMSCs and BMMSCs, have high cell viability in response to DOX, similar to the MES-SA/DX5 lineage. ABCB1 was less expressed in BM than in AFMSCs in undifferentiated samples, while no differences were observed in the expression of ABCC1 and LRP. AFMSCs showed an increase in ABCB1 after osteogenic differentiation, whereas BMMSCs exhibited lower ABCB1 and ABCC1 expression after osteogenic and adipogenic differentiation. The findings suggest that ABCB1, ABCC1, and LRP gene expression in AFMSCs and BMMSCs is influenced by differentiation processes and further support the concept that these transporters modulate MSC differentiation in a cell source-dependent way.
Authors
- Alexandre Fogaça Cristante (ORCID: https://orcid.org/0000-0002-7797-5274)
- Tarcísio Eloy Pessoa de Barros Filho (ORCID: https://orcid.org/0000-0002-7969-7845)
- Sérgio Paulo Bydlowski (ORCID: https://orcid.org/0000-0002-7582-5942)
- Marco Antônio Borges Lopes (ORCID: https://orcid.org/0000-0003-4517-7726)
- Felipe de Lara Janz (ORCID: https://orcid.org/0000-0002-6107-4375)
- Carolina Martinez Romão
- Débora Levy (ORCID: https://orcid.org/0000-0001-7492-997X)
- Jorge Luis Maria Ruiz
Institutions
- Universidade Federal da Integração Latino-Americana (BR)
- Universidade de São Paulo (BR)
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (BR)
- Hospital Sírio-Libanês (BR)
- National Institute of Science and Technology in Regenerative Medicine (BR)
- Universidade Estadual de Ponta Grossa (BR)
Publication Details
- Journal
- International Journal of Molecular Sciences
- Published
- 2025-01-09
- DOI
- https://doi.org/10.3390/ijms26020510
- Citations
- 2
- Primary Topic
- Mesenchymal stem cell research
- Type
- article
- Field-Weighted Citation Impact
- 3.25