Improved Delivery and Function of Myoblasts via Soluble TIPS Microcarriers

通过可溶性 TIPS 微载体改善成肌细胞的递送和功能

• 批准号: MR/L002752/1
• 负责人: Richard Day
• 金额: $ 60.55万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FL002752%2F1
• 关键词: Improved; Delivery; Function; Myoblasts; via

Incontinence is a debilitating condition with devastating social, economic and psychological consequences. A common cause is damage sustained during childbirth to the muscles that normally provide control of bowel movements. Current medical and surgical treatments are often inadequate. Emerging treatments involving the use of a patient's own muscle cells offer the possibility of restoring function to the damaged muscle, but improved methods for delivering the cells to ensure they survive and repair tissue are needed. The aim of the proposed research is to demonstrate, through proof of principle, that muscle cells attached to the surface of a unique type of degradable polymer microsphere are more effective at restoring injured muscle compared with conventional methods of muscle cell delivery. The aim will be achieved through an interdisciplinary project involving biologists, clinicians and materials scientists. The experimental study will include investigating the optimal conditions for attachment of muscle cells to the microspheres; delivery of the cellularized microspheres to pre-clinical models of muscle injury; measurement of integration of the transplanted cells at the injury site; and ability of the transplanted cells to restore muscle contractility. In parallel to the experimental study we will establish women's views on the innovative therapy we are proposing, which will help us to design a therapeutic system best suited to the user's needs. The outcome from the present study will provide timely, key information for the future development of the therapeutic system. The experimental outputs will be used to design future clinical trials investigating the safety and effectiveness of the treatment in faecally incontinent patients. Both the polymer microspheres and cell types being investigated are already being developed independently for other clinical uses, making transfer of findings from this project to the clinic for faecal incontinence much faster. If successful, the therapeutic system will have tremendous economic benefits to the UK NHS, as well as delivering social, economic and psychological benefits to patients.

尿失禁是一种使人衰弱的疾病，具有毁灭性的社会、经济和心理后果。一个常见的原因是分娩时控制排便的肌肉受到损伤。目前的医疗和手术治疗往往不足。新兴的治疗方法包括使用患者自身的肌肉细胞，为恢复受损肌肉的功能提供了可能，但需要改进运送细胞的方法，以确保它们存活并修复组织。拟议研究的目的是通过原理证明，与传统的肌肉细胞输送方法相比，附着在一种独特类型的可降解聚合物微球表面的肌肉细胞在恢复受伤肌肉方面更有效。这一目标将通过涉及生物学家、临床医生和材料科学家的跨学科项目来实现。实验研究将包括研究肌肉细胞附着在微球上的最佳条件；细胞化微球输送至临床前肌肉损伤模型；损伤部位移植细胞整合的测量；以及移植细胞恢复肌肉收缩力的能力。在实验研究的同时，我们将建立女性对我们提出的创新疗法的看法，这将有助于我们设计出最适合用户需求的治疗系统。本研究的结果将为未来治疗系统的发展提供及时、关键的信息。实验结果将用于设计未来的临床试验，调查治疗大便失禁患者的安全性和有效性。正在研究的聚合物微球和细胞类型已经被独立开发用于其他临床用途，这使得该项目的发现更快地转移到粪便失禁的临床。如果成功，该治疗系统将为英国国民医疗服务体系带来巨大的经济效益，并为患者带来社会、经济和心理上的好处。

项目成果

A novel method for differentiation of human mesenchymal stem cells into smooth muscle-like cells on clinically deliverable thermally induced phase separation microspheres.

• DOI: 10.1089/ten.tec.2014.0431
• 发表时间: 2015-04
• 期刊: Tissue engineering. Part C, Methods
• 作者: N. Parmar;R. Ahmadi;R. Day

Human artificial chromosomes for Duchenne muscular dystrophy and beyond: challenges and hopes.

用于治疗杜氏肌营养不良症及其他疾病的人类人工染色体：挑战和希望。

• DOI: 10.1007/s10577-014-9460-6
• 发表时间: 2015
• 期刊: an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology
• 作者: Tedesco FS

Biomaterials for hollow organ tissue engineering.

• DOI: 10.1186/s13069-016-0040-6
• 发表时间: 2016
• 期刊: Fibrogenesis & tissue repair
• 作者: Hendow EK;Guhmann P;Wright B;Sofokleous P;Parmar N;Day RM
• 通讯作者: Day RM

A simple and robust method for pre-wetting poly (lactic-co-glycolic) acid microspheres.

• DOI: 10.1177/0885328215577297
• 发表时间: 2015-08
• 期刊: Journal of biomaterials applications
• 影响因子: 2.9
• 作者: Wright B;Parmar N;Bozec L;Aguayo SD;Day RM
• 通讯作者: Day RM

TIPS to manipulate myogenesis: retention of myoblast differentiation capacity using microsphere culture.

操纵肌生成的技巧：使用微球培养保留成肌细胞分化能力。

• DOI: 10.22203/ecm.v030a04
• 发表时间: 2015
• 期刊: European cells & materials
• 影响因子: 3.1
• 作者: Parmar N