Abstract

LIGHT (HVEM-L, TNFSF14, or CD258), an entity homologous to lymphotoxins, with inducible nature and the ability to compete with herpes simplex virus glycoprotein D for herpes virus entry mediator (HVEM)/tumor necrosis factor (TNF)-related 2, is a member of the TNF superfamily. It is expressed as a homotrimer on activated T cells and dendritic cells (DCs), and has three receptors: HVEM, LT-β receptor (LTβR), and decoy receptor 3 (DcR3). So far, three receptors with distinct cellular expression patterns are known to interact with LIGHT. Follicular DCs and stromal cells bind LIGHT through LTβR. We monitored the effects of LIGHT on human bone marrow-derived mesenchymal stem cells (BM-MSCs). At first, we checked the negative and positive differentiation markers of BM-MSCs. And we confirmed the quality of MSCs by staining cells undergoing adipogenesis (Oil Red O staining), chondrogenesis (Alcian blue staining), and osteogenesis (Alizarin red staining). After rhLIGHT treatment, we monitored the count, viability, and proliferation of cells and cell cycle distribution. PDGF and TGFβ production by rhLIGHT was examined by ELISA, and the underlying biological mechanisms were studied by immunoblotting by rhLIGHT treatment. LTβR was constitutively expressed on the surface of human BM-MSCs. Cell number and viability increased after rhLIGHT treatment. BM-MSC proliferation was induced by an increase in the S/G2/M phase. The expression of not only diverse cyclins such as cyclin B1, D1, D3, and E, but also CDK1 and CDK2, increased, while that of p27 decreased, after rhLIGHT treatment. RhLIGHT-induced PDGF and TGFβ production mediated by STAT3 and Smad3 activation accelerated BM-MSC proliferation. Thus, LIGHT and LTβR interaction increases the survival and proliferation of human BM-MSCs, and therefore, LIGHT might play an important role in stem cell therapy.

Highlights

  • Mesenchymal stem cells (MSCs), a type of adult stem cells, are self-renewing, multipotent cells capable of differentiating into multiple cell types such as adipocytes, chondrocytes, and osteocytes [1,2,3]

  • bone marrow-derived mesenchymal stem cells (BM-MSCs) were determined phenotypically and their ability to differentiate into mature mesodermal cell types was apparent (Fig 1)

  • Many basic studies showed the brilliant results of MSC-based therapeutic plans, including myocardial infarcts [32], diabetes [33], neurological disorders [5,7], and graft-versus-host disease (GVHD) [7,12]

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Summary

Introduction

Mesenchymal stem cells (MSCs), a type of adult stem cells, are self-renewing, multipotent cells capable of differentiating into multiple cell types such as adipocytes, chondrocytes, and osteocytes [1,2,3]. They can be found in many tissues such as the bone marrow (BM), skeletal muscle, dental pulp, bone, umbilical cord, and adipose tissue [2,4]. Only low cell numbers (1–10 of 1 × 105 nucleated cells) have been obtained from healthy volunteers by BM aspiration [7].

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