Modulation of mesenchymal stem cells by hyaluronan and sulfated derivatives in osteosarcoma

ICARDI, ANTONELLA; SEVIC, INA; SPINELLI, FIORELLA; VITALE, DAIANA; VALENZUELA ALVAREZ, MATIAS; GUTIERREZ, LUCIANA M.; GARCIA, MARIANA; BOLONTRADE, MARCELA F.; ALANIZ, LAURA

Mar del PLata

Congreso; Reunión Conjunta de Sociedades de Biociencias, LXIV Reunión Anual SAIC, Sociedad Argentina de Investigación Clínica. SAI. SAFIS; 2019

SAIC

The treatment and reconstruction of bone in osteosarcoma, after tumor resection, remains a challenge. A promising therapy is the therapeutic use of mesenchymal stem cells (MSCs). Since hyaluronan (HA) is a component of the extracellular matrix, MSCs can interact with HA affecting the differentiation of these cells in therapeutic applications.Aim: To evaluate the therapeutic effect in osteosarcoma of MSCs derived from umbilical cord (hUC-MSCs) treated with HA or its sulfated derivatives (sHA). Also, the role in tissue remodeling and as well as in tumor behavior.Methods: Viability and apoptosis assays by MTS and AnnexinV/IP by flow cytometry were used to determine the dose of HA or sHA to treat hUC-MSCs. Mixed lymphocytes cultures (MLC) were performed to evaluate the effect of HA or sHA on the immunogenicity of hUC-MSCs. The effect of these biomaterials on the bone regenerative capacity of hUC-MSCs was analyzed by differentiation assays. Finally, the effect of conditioned media (CM) of hUC-MSCs treated with HA or sHA on the Saos-2 was analyzed by cellular viability analysis.Results: hUC-MSCs exhibited low immunogenicity under MLC conditions and retained their immune properties after treatment with HA or sHA. HA or sHA reduced differentiation towards adipogenic lineage in vitro, in a dose-dependent mannerand associated with theHA sulfation levels. Regarding the capacity for hUC-MSCsosteogenic differentiation,HA treatments showed a tendency to increase in comparison to control. The CM derived from hUC-MSCs had a pro-tumor effect, but the effect decreased when the cells were treated with HA or sHA by decreasing cell viability.Conclusion: The hUC-MSCs are permissive for allogeneic transplantation. However, our results suggest HA and sHAtreatments reduced the ability of hUC-MSCs to differentiate towards the adipogenic lineage. Besides, in tumor context favor the tumor behavior of Saos-2, but this effect diminished with HA or sHA treatments.