干细胞领域知识发现平台

提升科研信息化水平
支撑研究所科技创新

  融合多源信息    打通数据孤岛
  挖掘知识关联    放大数据价值
  集成知识计算    促进知识发现

免费注册账号
查看全文和研发动态、知识导航以及收藏您喜欢的数据等操作,您需要注册一个免费帐户并登录。

写笔记

您最近的笔记
Chemically modified RNA induces osteogenesis of stem cells and human tissue explants as well as accelerates bone healing in rats.
Biomaterials, Issue: , Volume: 87, Pages: 131-146. | 2016-01-05
0 Patent citations    10 Scholarly citations     Reference Count: 45
Elizabeth R Balmayor;Johannes Geiger;Manish Kumar Aneja;Taras Berezhanskyy;Maximilian Utzinger;Olga Mykhaylyk;Carsten Rudolph;Christian Plank

摘要

Abstract Limitations associated to the use of growth factors represent a major hurdle to musculoskeletal regeneration. On the one hand, they are needed to induce neo-tissue formation for the substitution of a necrotic or missing tissue. On the other hand, these factors are used in supraphysiological concentrations, are short lived and expensive and result in many side effects. Here we develop a gene transfer strategy based on the use of chemically modified mRNA (cmRNA) coding for human bone morphogenetic protein 2 (hBMP-2) that is non-immunogenic and highly stable when compared to unmodified mRNA. Transfected stem cells secrete hBMP-2, show elevated alkaline phosphatase levels and upregulated expression of RunX2, ALP, Osterix, Osteocalcin, Osteopontin and Collagen Type I genes. Mineralization was induced as seen by positive Alizarin red staining. hBMP-2 cmRNA transfected human fat tissue also yielded an osteogenic response in vitro as indicated by expression of hBMP-2, RunX2, ALP and Collagen Type I. Delivering hBMP-2 cmRNA to a femur defect in a rat model results in new bone tissue formation as early as 2 weeks after application of very low doses. Overall, our studies demonstrate the feasibility and therapeutic potential of a new cmRNA-based gene therapy strategy that is safe and efficient. When applied clinically, this approach could overcome BMP-2 growth factor associated limitations in bone regeneration.


机构

Technische Universität München;Institute of Molecular Immunology and Experimental Oncology, Technical University Munich, Ismaninger Str. 22, 81675 Munich, Germany; Ethris GmbH, Semmelweisstr. 3, 82152 Planegg, Germany; Experimental Trauma Surgery, Klinikum rechts der Isar, Technical University Munich, Ismaninger Str. 22, 81675 Munich, Germany. Electronic address: Elizabeth.rosado-balmayor@tum.de.Ludwig Maximilian University of Munich;Ethris GmbH, Semmelweisstr. 3, 82152 Planegg, Germany.Ludwig Maximilian University of Munich;Ethris GmbH, Semmelweisstr. 3, 82152 Planegg, Germany.Technische Universität München;Institute of Molecular Immunology and Experimental Oncology, Technical University Munich, Ismaninger Str. 22, 81675 Munich, Germany; Ethris GmbH, Semmelweisstr. 3, 82152 Planegg, Germany.Ludwig Maximilian University of Munich;Ethris GmbH, Semmelweisstr. 3, 82152 Planegg, Germany.Technische Universität München;Institute of Molecular Immunology and Experimental Oncology, Technical University Munich, Ismaninger Str. 22, 81675 Munich, Germany; Ethris GmbH, Semmelweisstr. 3, 82152 Planegg, Germany.Ludwig Maximilian University of Munich;Ethris GmbH, Semmelweisstr. 3, 82152 Planegg, Germany.Technische Universität München;Institute of Molecular Immunology and Experimental Oncology, Technical University Munich, Ismaninger Str. 22, 81675 Munich, Germany; Ethris GmbH, Semmelweisstr. 3, 82152 Planegg, Germany. Electronic address: plank@ethris.com.


文献类型:

journal article;research support, non-u.s. gov't;

出版商:

Elsevier BV

发表时间:

2016-01-05

基金信息

DFG Research Unit FOR917()