BONE MARROW MESENCHYMAL STEM CELLS DERIVED FROM HEALTHY DONORS BUT NOT THOSE DERIVED FROM ACUTE MYELOID LEUKEMIA PATIENTS ARE ABLE TO AFFECT PROLIFERATION AND DEATH OF LEUKEMIC CELL LINEAGES K562 AND K562 LUCENA

Abstract

<h3>Background</h3> In bone marrow (BM), mesenchymal stem cells (MSC) are a rare cell population. Beyond that, BM-MSCs play an important role in the maintenance of medullary niche and in supporting hematopoiesis. However, BM MSCs from patients with leukemia seems to participate in the disease progression and relapse. In this study we have evaluated in vitro some aspects of the influence of BM MSCs derived from healthy donors and acute myeloid leukemia (AML) patients on leukemic cell lines K562 (sensitive to vincristine) and K562 Lucena (multidrug resistance phenotype - MDR), as measured by the proliferation rates and death characteristics. <h3>Methods</h3> BM-MSCs were obtained from 3 healthy donors and 3 AML patients after written informed consent. K562 and K562-Lucena cell lines were co-cultured with BM-MSCs in a transwell system by 48 h. After incubation, leukemic cells (K562 and K562-Lucena) were evaluated for proliferation, viability, apoptosis, and necrosis by fluorescent methodology in a High-content Screening platform. <h3>Results</h3> Healthy BM-MSCs were shown to decrease proliferation of both K562 and K562-Lucena cell lines (37% and 42%, respectively) and viability (42% and 28%, respectively), while increased cell death rates through apoptosis (80% and 140%, respectively) and necrosis (28 fold and 32 fold, respectively) mechanisms, when compared with their respective controls. However, these effects were not observed when leukemic cells K562 and K562-Lucena were co-cultured with AML-BM-MSC. <h3>Conclusion</h3> BM-MSC derived from healthy donors decreased K562 and K562-Lucena cell lines proliferation and viability, while increased their apoptosis and necrosis rates. However, AML-BM-MSC did not affected proliferation, viability, and cell death rates of K562 and K562-Lucena cell lines. In conclusion, AML-BM-MSCs seem to lose the capacity to control proliferation and death capacity of leukemic cells. Information on ethical approval and funding support: This work was approved by Comitê de Ética em Pesquisa (CEP) of HC-FMUSP and supported by grants from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES); Instituto Nacional de Ciência e Tecnologia – Fluidos Complexos (INCT-FCx); Instituto Nacional de Ciência e Tecnologia em Medicina Regenerativa (INCT-Regenera).