The role of melatonin preconditioning on survival of bone marrow-derived mesenchymal stem cells in differentiation to osteoblasts

Abstract EN

Background : Preconditioning has become an increasingly promising strategy and applied in cell therapy and shows multiple therapeutic benefits in several diseases.

Some bioactive agents, such as hormones, are utilized to a develop cell therapy outcome.

Melatonin is secreted from the pineal gland and is famous for its antioxidant capability and cytoprotection potential.

Evidence suggest that melatonin may play an important role in the regulation of mesenchymal stem cells (MSCs) differentiation to osteoblasts.

Objectives : The aim of this study was to evaluate the influence of melatonin preconditioning on the differentiation of bone marrow derived mesenchymal stem cells (BM-MSCs) to osteoblasts.

Methods : This experimental study was performed at molecular genetic and embryology laboratories of Hamadan University of Medical Sciences, Hamadan, Iran, from October 2015 to April 2017.

The bone marrow stem cells (BMSCs) were obtained, cultured, expanded, and preconditioned with 5 M melatonin and analyzed for their multi-potency and immunophenotypic potential at passage five.

There were three groups composed of the control group BMSCs + osteogenic medium group, and melatonin-bone marrow stem cells (MT-BMSCs) group.

The BMSCs and MT-BMSCs were cultivated in an osteogenic medium.

After three weeks of cell survival, osteogenic capability and apoptosis were assessed in three groups.

Results : Bone marrow-derived mesenchymal stem cells expressed CD44 and CD90, yet not CD45 and showed differentiation to adipocytes and osteoblast.

The BMSCs were preconditioned withMT expressed metallothionein 1 (MT1) and metallothionein 2 (MT2) (P < 0.05).

Group three showed lower expression of Bax gene yet higher expression of Bcl2 (P < 0.05).

Group three had a high ability of osteogenic differentiation capability and reduced apoptosis.

Conclusions : The current study detected that melatonin pretreatment promotes MSC survival, reduce apoptosis, and has a positive effect on osteogenic factors in vitro.

The preconditioning strategy may represent a safe approach to improve the beneficial effects of stem cell therapy in bone regenerative medicine.