Abstract

Stem cell-based regeneration therapy offers new therapeutic options for patients with bone defects because of significant advances in stem cell research. Although bone marrow mesenchymal stem cells are the ideal material for bone regeneration therapy using stem cell, they are difficult to obtain. Induced pluripotent stem cells (iPSCs) are now considered an attractive tool in bone tissue engineering. Recently, the efficiency of establishing iPSCs has been improved by the use of the Sendai virus vector, and it has become easier to establish iPSCs from several type of somatic cells. In our previous study, we reported a method to purify osteogenic cells from iPSCs.Objective:This study aimed to evaluate the osteogenic ability of iPSCs derived from peripheral blood cells.Methodology:Mononuclear cells (MNCs) were obtained from human peripheral blood. Subsequently, T cells were selectively obtained from these MNCs and iPSCs were established using Sendai virus vectors. Established iPSCs were evaluated by the expression of undifferentiated markers and teratoma formation assays. Osteoblasts were induced from these iPSCs and evaluated by the expression of osteoblast markers. Additionally, the induced osteoblasts were transplanted into rat critical size calvaria bone defect models with collagen sponge scaffolds. Samples were evaluated by radiographical and histological assessments.Results:Induced osteoblasts expressed several osteoblast-specific markers. The results of radiographical and histological assessments revealed that the cell transplant group had bone formations superior to those of the control group.Conclusions:This study suggests that peripheral blood MNCs have the potential to differentiate into osteoblasts. Although there are some hurdles in iPSC transplantation, osteoblasts obtained from MNC-iPSCs could be applied to bone regeneration therapy in the future.

Highlights

  • In the oral and maxillofacial region, bone grafts are required for patients with congenital diseases, such as a cleft lip or palate, and for patients who have acquired bone defects resulting from surgical procedures.[1-5]Autogenous bone grafting remains the “gold standard” for extensive bone reconstructions because of the osteogenic, osteoinductive, and osteoconductive properties of this method.[2]

  • T cells were selectively obtained from these Mononuclear cells (MNCs) and Induced pluripotent stem cells (iPSCs) were established using Sendai virus vectors

  • There are some hurdles in iPSC transplantation, osteoblasts obtained from MNC-iPSCs could be applied to bone regeneration therapy in the future

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Summary

Introduction

In the oral and maxillofacial region, bone grafts are required for patients with congenital diseases, such as a cleft lip or palate, and for patients who have acquired bone defects resulting from surgical procedures.[1-5]Autogenous bone grafting remains the “gold standard” for extensive bone reconstructions because of the osteogenic, osteoinductive, and osteoconductive properties of this method.[2]. In the oral and maxillofacial region, bone grafts are required for patients with congenital diseases, such as a cleft lip or palate, and for patients who have acquired bone defects resulting from surgical procedures.[1-5]. There are expectations that stem cells may enable a new form of bone regenerative therapy instead of the autogenous bone graft treatment. It has been reported that regenerative therapy can be achieved by stem cells, scaffolding, and cytokines. In recent studies on this topic, the interaction between stem cells and biomaterials has emerged as a topic of interest, and it has been found that the secretome produced by stem cells has various physiological and biological effects in stem cell transplantation. The current strategy is to create new scaffolds for stem cell transplantation based on computer-aided design (CAD) technology.[7]. Stem cells are identified according to their source, for example, bone marrow mesenchymal stem cells (MSCs), adipoderived MSCs, perivascular stem cells, and induced pluripotent stem cells (iPSCs).[8]

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