Improved Delivery and Function of Myoblasts via Soluble TIPS Microcarriers

大小便失禁是一种衰弱的疾病，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期间通常控制肠道运动的肌肉受损。目前的内科和外科治疗往往是不够的。使用患者自己的肌肉细胞的新兴治疗方法提供了恢复受损肌肉功能的可能性，但改进了输送细胞的方法，以确保它们存活并修复组织。这项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，附着在独特类型的可降解聚合物微球表面的肌肉细胞在修复受损肌肉方面更有效。这一目标将通过一个涉及生物学家、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；将细胞化的微球输送到肌肉损伤的临床前模型；测量损伤部位移植细胞的整合；以及移植细胞恢复肌肉收缩能力的能力。在进行实验研究的同时，我们将确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。本研究的结果将为治疗系统的未来发展提供及时的关键信息。实验结果将用于设计未来的临床试验，调查该疗法在大便失禁患者中的安全性和有效性。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，使得该项目的研究成果更快地转移到临床上治疗大便失禁。如果成功，该治疗系统将为英国NHS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。

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.