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Using drugs, machines, and genes to engineer functional muscle

使用药物、机器和基因来设计功能性肌肉

基本信息

批准号：
EP/E008925/1
负责人：
Robert Keatch
金额：
$ 27.73万
依托单位：
University of Dundee
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2007
资助国家：
英国
起止时间：
2007 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FE008925%2F1
关键词：
Using drugs machines genes engineer

项目摘要

The goal of tissue engineering is to use scaffolding materials and multipotent stem cells to produce tissue replacements. In engineering muscle, this is made more complex by the fact that the function of muscle is to produce force and therefore the scaffold has to be compliant and biodegradable. While great progress has been made towards this goal, a number of obstacles remain, including: 1) vascularization of the engineered muscle; 2) creation of effective interfaces between muscle and bone/artificial materials; 3) maturation of the muscle, since it is developmentally arrested; and 4) the development of normal muscle fibre size and strength. The result is that the current state-of-the-art tissue engineered muscles are 0.2mm thick and produce at best 35% of the relative force of a neonatal muscle. In order to make the engineered muscles bigger and increase their force production, we propose to use drugs to remove inhibitors of muscle growth and development, machines to stretch and electrically stimulate muscle growth and development, and genes to increase muscle fibre size and therefore force production. The research combines discoveries made in vivo studying muscle physiology with our engineered muscle model to try to make bigger, stronger and more adult muscle in culture.

组织工程的目标是利用支架材料和多能干细胞来产生组织替代物。在肌肉工程中，这一点变得更加复杂，因为肌肉的功能是产生力，因此支架必须是顺应性和可生物降解的。虽然朝着这一目标已经取得了很大进展，但仍然存在许多障碍，包括：1）工程肌肉的血管化; 2）在肌肉和骨/人造材料之间建立有效的界面; 3）肌肉的成熟，因为它在发育上被阻止;以及4）正常肌纤维尺寸和强度的发展。结果是，目前最先进的组织工程肌肉厚度为0.2毫米，最多只能产生新生肌肉相对力量的35%。为了使工程肌肉更大并增加其力量产生，我们建议使用药物来消除肌肉生长和发育的抑制剂，使用机器来拉伸和电刺激肌肉生长和发育，并使用基因来增加肌肉纤维大小，从而增加力量产生。这项研究将体内肌肉生理学研究的发现与我们的工程肌肉模型相结合，试图在培养中制造更大、更强、更成熟的肌肉。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Absence of the Birt-Hogg-Dubé gene product is associated with increased hypoxia-inducible factor transcriptional activity and a loss of metabolic flexibility.

DOI：
10.1038/onc.2010.497
发表时间：
2011-03-10
期刊：
ONCOGENE
影响因子：
8
作者：
Preston, R. S.;Philp, A.;Claessens, T.;Gijezen, L.;Dydensborg, A. B.;Dunlop, E. A.;Harper, K. T.;Brinkhuizen, T.;Menko, F. H.;Davies, D. M.;Land, S. C.;Pause, A.;Baar, K.;van Steensel, M. A. M.;Tee, A. R.
通讯作者：
Tee, A. R.

Optimizing an Intermittent Stretch Paradigm Using ERK1/2 Phosphorylation Results in Increased Collagen Synthesis in Engineered Ligaments

DOI：
10.1089/ten.tea.2011.0336
发表时间：
2012-02-01
期刊：
TISSUE ENGINEERING PART A
影响因子：
4.1
作者：
Paxton, Jennifer Z.;Hagerty, Paul;Baar, Keith
通讯作者：
Baar, Keith

Pyruvate suppresses PGC1alpha expression and substrate utilization despite increased respiratory chain content in C2C12 myotubes.

DOI：
10.1152/ajpcell.00438.2009
发表时间：
2010-08
期刊：
American journal of physiology. Cell physiology
影响因子：
0
作者：
Philp A;Perez-Schindler J;Green C;Hamilton DL;Baar K
通讯作者：
Baar K

Factors affecting the longevity and strength in an in vitro model of the bone-ligament interface.

DOI：
10.1007/s10439-010-0044-0
发表时间：
2010-06
期刊：
ANNALS OF BIOMEDICAL ENGINEERING
影响因子：
3.8
作者：
Paxton, Jennifer Z.;Donnelly, Kenneth;Keatch, Robert P.;Baar, Keith;Grover, Liam M.
通讯作者：
Grover, Liam M.

Biomaterials in regenerative medicine: engineering to recapitulate the natural.