RESUMO

Cancer is understood as a multifactorial disease that involve multiple cell types and phenotypes in the tumor microenvironment (TME). The components of the TME can interact directly or via soluble factors (cytokines, chemokines, growth factors, extracellular vesicles, etc.). Among the cells composing the TME, mesenchymal stem cells (MSCs) appear as a population with debated properties since it has been seen that they can both promote or attenuate tumor progression. For various authors, the main mechanism of interaction of MSCs is through their secretome, the set of molecules secreted into the extracellular milieu, recruiting, and influencing the behavior of other cells in inflammatory environments where they normally reside, such as wounds and tumors. Natural products have been studied as possible cancer treatments, appealing to synergisms between the molecules in their composition; thus, extracts obtained from Petiveria alliacea (Anamu-SC) and Caesalpinia spinosa (P2Et) have been produced and studied previously on different models, showing promising results. The effect of plant extracts on the MSC secretome has been poorly studied, especially in the context of the TME. Here, we studied the effect of Anamu-SC and P2Et extracts in the human adipose-derived MSC (hAMSC)-tumor cell interaction as a TME model. We also investigated the influence of the hAMSC secretome, in combination with these natural products, on tumor cell hallmarks such as viability, clonogenicity, and migration. In addition, hAMSC gene expression and protein synthesis were evaluated for some key factors in tumor progression in the presence of the extracts by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Multiplex, respectively. It was found that the presence of the hAMSC secretome did not affect the cytotoxic or clonogenicity-reducing activities of the natural extracts on cancer cells, and even this secretome can inhibit the migration of these tumor cells, in addition to the fact that the profile of molecules can be modified by natural products. Overall, our findings demonstrate that hAMSC secretome participation in TME interactions can favor the antitumor activities of natural products.

Assuntos

Células-Tronco Mesenquimais , Extratos Vegetais , Secretoma , Humanos , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Secretoma/metabolismo , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Células Cultivadas , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais

RESUMO

Mesenchymal stem cells are a tool in cell therapies but demand a large cell number per treatment, for that, suitable culture media is required which contains fetal bovine serum (FBS). However, for cell-based therapy applications, the use of FBS is problematic. Several alternatives to FBS have been explored, including human derivatives from platelet-rich plasma (hD-PRP). Although various studies have evaluated the impact of hD-PRP on MSC proliferation and differentiation, few of them have assessed their influence on processes, such as metabolism and gene expression. Here, we cultured human adipose-derived MSCs (hAD-MSCs) in media supplemented with either 10% hD-PRP (hD-PRP-SM) or 10% FBS (FBS-SM) in order to characterize them and evaluate the effect of hD-PRP on cell metabolism, gene expression of associated regenerative factors, as well as chromosome stability during cell expansion. We found that hAD-MSCs cultured in hD-PRP-SM have a greater cell elongation but express similar surface markers; in addition, hD-PRP-SM promoted a significant osteogenic differentiation in the absence of differentiation medium and increased the growth rate, maintaining chromosomal stability. In terms of cell metabolic profile, hAD-MSC behavior did not reveal any differences between both culture conditions. Conversely, significant differences in collagen I and angiopoietin 2 expression were observed between both conditions. The present results suggest that hD-PRP may influence hAD-MSC behavior.

Assuntos

Células-Tronco Mesenquimais , Plasma Rico em Plaquetas , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Humanos , Células-Tronco Mesenquimais/metabolismo , Osteogênese , Plasma Rico em Plaquetas/metabolismo

RESUMO

OBJECTIVE: The objective of this study was to compare platelet-rich plasma (PRP), bone marrow aspirate concentrate (BMAC), and adipose-derived mesenchymal stem cell (MSC) injections in the treatment of osteoarthritis (OA) of the knee using functional scores. METHODS: A total of 89 patients with painful knee OA were included in this study. Patients were assigned to one of the 3 treatments according to severity of OA as indicated by symptoms and radiography to PRP (stage I), BMAC (stage II), or adipose-derived MSC (stage III). Clinical assessment was performed using the Knee Society Score, which combines the Knee Score, based on the clinical parameters, and the Functional Score, and IKDC score. Surveys were completed at preoperative and at 90, 180, and 265 days postoperative. The follow-up responses were compared with baseline and between treatment groups. RESULTS: Treatment with PRP, BMAC, and adipose-derived MSC included 29 (32.6%), 27 (30.3%), and 33 (37.1%) patients, respectively. For the total group, median age was 61 years (range: 22-84 years). Score values were comparable among treatment groups at baseline. Statistically significant improvement was observed in the 3 groups according to the 3 scores at all time points during follow-up compared with baseline. No difference was found among treatment type. CONCLUSIONS: Our findings support previous reports and encourage further research on the use of these cost-effective treatments for OA of the knee.