Malignant Melanoma is known for being one of the most aggressive cancers with an incidence that increases every year. Cancer stem cells (CSCs) are involved in the resistance to therapeutic treatments, the metastatic process, and the patient’s relapses. Thus, it is of vital importance for researchers to find the methodology that allows us to obtain enriched subpopulations that maintain their stem-like properties without differentiating over time. In the present manuscript, our objective was to compare the ability of conditioned medium obtained from human mesenchymal stem cells (MSCs) isolated by enzymatic and non-enzymatic methods for the enrichment and maintenance of melanoma CSCs. Our results showed for the first time that MSCs isolated by less aggressive methodology displayed higher CSCs enrichment and maintenance capacity. Because they do not undergo enzymatic and proteolytic stress, MSCs produce a greater amount of signalling molecules, helping to improve the phenotype characteristics of CSCs and keep them over time.
