プロジェクトのご紹介 5 - Project 5 -
TGFR阻害剤による骨芽細胞のケミカル・ダイレクト・リプログラミング
Chemical direct reprogramming of human fibroblasts into osteoblasts by a TGFR blockade
A procedure to generate functional osteoblasts from human somatic cells may pave the way to a novel and effective transplantation therapy in bone disorders. Here, we report that human fibroblasts were induced to show osteoblast phenotypes by culturing with ALK5 i II, which is a specific inhibitor for activin-like kinase 5 (ALK5) (tumor growth factor-β receptor 1 (TGF-β R1)). Cells cultured with ALK5 i II expressed osteoblast-specific genes and massively produced calcified bone matrix, similar to the osteoblasts induced from mesenchymal stem cells (MSC-OBs). Treatment with vitamin D3 in addition to ALK5 i II induced more osteoblast-like characters, and the efficiency of the conversion reached approximately 90%. The chemical compound-mediated directly converted osteoblasts (cOBs) were similar to human primary osteoblasts in terms of expression profiles of osteoblast-related genes. The cOBs abundantly produced bone matrix in vivo and facilitated bone healing after they were transplanted into immunodeficient mice at an artificially induced defect lesion in femoral bone. The present procedure realizes a highly efficient direct conversion of human fibroblasts into transgene-free and highly functional osteoblasts, which might be applied in a novel strategy of bone regeneration therapy in bone diseases.
Kenta Yamamoto, Tsunao Kishida, et al. Scientific Reports
一部プロジェクトのご紹介 - See some projects among others -
- 新型コロナウイルス・オミクロン変異株に対する茶カテキン類の効果
Effects of tea catechin-related compounds on Omicron subvariants of SARS-CoV-2 - 腫瘍微小環境の低pHはプロトンセンサーGたんぱく共役レセプターをを介して腫瘍のPDL-1の発現を低下させる
Extracellular acidity in tumor tissue upregulates programmed cell death protein 1 expression on tumor cells via proton-sensing G protein-coupled receptors - 緑茶カテキン、カテキン誘導体、およびガレート型テアフラビンによる新型コロナウイルスの試験管内での有意な不活化；紅茶と緑茶による試験管内での唾液中の新型コロナウイルスの迅速な不活化
Significant Inactivation of SARS-CoV-2 by a Green Tea Catechin, a Catechin-derivative and Galloylated Theaflavins in vitro; Rapid Inactivation in vitro of SARS-CoV-2 in Saliva by Black Tea and Green Tea - 新規多孔性３Dスキャフォールドと直接誘導骨芽細胞を用いた骨再生
Nanogel tectonic porous 3D scaffold for direct reprogramming fibroblasts into osteoblasts and bone regeneration - TGFR阻害剤による骨芽細胞のケミカル・ダイレクト・リプログラミング
Chemical direct reprogramming of human fibroblasts into osteoblasts by a TGFR blockade - 筋芽細胞のダイレクト・リプログラミングと筋管形成
Direct reprogramming of functional myoblasts that are capable of forming multinuclear myotube - シュワン細胞のダイレクト・リプログラミングと末梢神経損傷の再生
Direct reprogramming of functional Schwann cells that promote regeneration of peripheral nerve - 褐色脂肪のダイレクト・リプログラミングと代謝疾患の制御
Direct reprogramming of functional brown adipocytes that control metabolic diseases - 骨芽細胞のダイレクト・リプログラミングと骨再生
Direct reprogramming of functional osteoblasts that regenerate bone tissue - IL-21 によるアレルギー応答の制御とその分子機構
IL-21-mediated regulation of allergic responses and its molecular mechanisms - IL-27 による NK 細胞活性化と ADCC を介した腫瘍抑制
IL-27 augments NK cytotoxicity and induces ADCC-based tumor suppression - EBV- エピゾーマルベクターによる外来遺伝子の高効率導入、高発現、長期間持続の機構解明
Mechanisms underlying the high-rate transfection, high-level expression, and long-term maintenance of exogenous genes mediated by the Epstein-Barr virus-based episomal vector - 細胞の分化と初期化に伴う染色体エピジェネティック修飾の解析
Analyses of epigenetic modification of chromosomes upon cell differentiation and reprogramming