Tokyo Dental College, Department of Oral and Maxillofacial Surgery, Tokyo, Japan.
The Jikei University School of Medicine, Department of Dentistry, Tokyo, Japan.
J Appl Oral Sci. 2022 Feb 21;30:e20210491. doi: 10.1590/1678-7757-2021-0491. eCollection 2022.
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.This study aimed to evaluate the osteogenic ability of iPSCs derived from peripheral blood cells.
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.
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.
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.
由于干细胞研究的重大进展，基于干细胞的再生疗法为骨缺损患者提供了新的治疗选择。虽然骨髓间充质干细胞是用于干细胞再生治疗的理想材料，但它们难以获得。诱导多能干细胞（iPSCs）现在被认为是骨组织工程中一种有吸引力的工具。最近，使用仙台病毒载体提高了建立 iPSCs 的效率，并且更容易从几种体细胞建立 iPSCs。在我们之前的研究中，我们报告了一种从 iPSCs 中纯化成骨细胞的方法。本研究旨在评估源自外周血细胞的 iPSCs 的成骨能力。
从人外周血中获得单核细胞（MNCs）。随后，从这些 MNCs 中选择性获得 T 细胞，并使用仙台病毒载体建立 iPSCs。通过未分化标志物的表达和畸胎瘤形成试验评估建立的 iPSCs。从这些 iPSCs 诱导成骨细胞，并通过成骨细胞标志物的表达进行评估。此外，将诱导的成骨细胞与胶原海绵支架一起移植到大鼠临界尺寸颅骨骨缺损模型中。通过影像学和组织学评估来评估样本。
诱导的成骨细胞表达了几种成骨细胞特异性标志物。影像学和组织学评估的结果表明，细胞移植组的骨形成优于对照组。
本研究表明外周血 MNC 具有分化为成骨细胞的潜力。尽管 iPSC 移植存在一些障碍，但从 MNC-iPSCs 获得的成骨细胞将来可应用于骨再生治疗。
