Abstract

Stem cell therapy is an evolving treatment strategy in regenerative medicine. Recent studies report stem cells from human exfoliated deciduous teeth could complement the traditional mesenchymal stem cell sources. Stem cells from human exfoliated deciduous teeth exhibit mesenchymal characteristics with multilineage differentiation potential. Mesenchymal stem cells are widely investigated for cell therapy and disease modeling. Although many research are being conducted to address the challenges of mesenchymal stem cell therapy in clinics, most of the studies are still in infancy. Host cell microenvironment is one of the major factors affecting the homing of transplanted stem cell and understanding the factors affecting the fate of stem cells of prime important. In this study we aimed to understand the effects of serum deprivation in stem cells derived from human deciduous tooth. Our study aimed to understand the morphological, transcriptional, cell cycle and stemness based changes of stem cells in nutrient deprived medium. Our results suggest that stem cells in nutrient deprived media undergo low proliferation, high apoptosis and changed the differentiation potential of the stem cells. Serum deprived mesenchymal stem cells exhibited enhanced chondrogenic differentiation potential and reduced osteogenic differentiation potential. Moreover, the activation of key metabolic sensor AMP-activated kinase (AMPK) leads to activation of transcription factors such as FOXO3, which leads to an S phase quiescence. Serum deprivation also enhanced the expression of stemness related genes Sox2 and c-Myc.

Highlights

  • Stem cell therapy is one of the promising clinical approaches which will be a game changer for treating many diseases

  • We analyzed the expression of Mesenchymal stem cells (MSCs) markers such as CD73, CD90, and CD105, and we found these cells presented positive marker expression for the MSC markers (Figure 1B–E), whereas non-MSC markers CD34, CD45 and MHC Class II antigen and HLA-DR showed negligible marker expression in stem cells from human exfoliated deciduous teeth (SHEDs) (Figure 1F–H)

  • SHEDs are mesenchymal cells derived from the exfoliated human deciduous teeth pulp and are widely under investigation for complementing the traditional MSC sources

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Summary

Introduction

Stem cell therapy is one of the promising clinical approaches which will be a game changer for treating many diseases. Genetic instability of stem cells, immunological rejection by host immune system, stem cell culturing conditions, pharmacokinetic behavior of stem cells and ethical issues are some of the challenges in stem cell therapy [1]. Most of the stem cell therapies are still in preclinical trial stage and require extensive research for implementing in clinics. Ethical issues associated with using embryonic stem cells (ESC) and human embryo limit the research. Postnatal isolation of stem cells can be carried out from various tissues such as hair follicles, bone marrow, muscles and dental pulp [2,3,4]. Miura et al, showed human deciduous tooth as a source of multipotent stem cells and these stem cells from human exfoliated deciduous teeth (SHEDs) exhibited mesenchymal characteristics [5]. SHEDs possess high multipotency, proliferative capacity, minimum risk of oncogenesis and minimum ethical concerns [7,8]

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