Novel Strategies in Bladder Tissue Engineering: Stem Cells and Silk Biomaterials

膀胱组织工程的新策略：干细胞和丝生物材料

• 批准号: 8728197
• 负责人: Joshua Robert Mauney
• 金额: $ 21.54万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8728197
• 关键词: Address; Advisory Committees; Autologous; Biocompatible Materials; Bladder; Bladder Tissue; Cell Culture Techniques; Cell Therapy; Cell physiology; Cells; Characteristics; Clinical; Clinical Trials; Defect; Genitourinary system; Goals; Grant; Hand; Human; Inner Cell Mass; Institution; Instruction; Interview; Laboratories; Manuscripts; Mechanics; Mentors; Methods; Modality; Modification; Muscle; Natural regeneration; Nature; Occupations; Operative Surgical Procedures; Organ; Patients; Phenotype; Pluripotent Stem Cells; Porosity; Positioning Attribute; Preparation; Property; Protocols documentation; Regenerative Medicine; Reporting; Research Personnel; Research Training; Silk; Smooth Muscle; Smooth Muscle Myocytes; Somatic Cell; Source; Stem cells; System; Techniques; Testing; Tissue Engineering; Tissues; Urethra; Variant; Writing; base; biomaterial compatibility; blastocyst; career development; embryonic stem cell; frontier; human embryonic stem cell; implantation; induced pluripotent stem cell; innovation; novel strategies; pluripotency; preimplantation; reconstruction; repaired; research study; restoration; scaffold; skills; stem; stem cell biology; stem cell population; tissue reconstruction; tissue regeneration; urologic

PROJECT SUMMARY/ABSTRACT My overall goal in this proposal is to address the current limitations in surgical options for bladder reconstruction while developing my professional abilities to transition into an independent investigator. My professional objective is to have a position as a lab director in a superb academic institution that will allow me to continue to expand the frontiers of regenerative medicine by creating innovative stem cell-based therapies for urological tissue reconstruction. My primary research training objectives will be to acquire new technical skills in urological tissue engineered systems and human pluripotent stem cell biology. This will be accomplished through additional fundamental coursework and hands on instruction in laboratory protocols and techniques as detailed in the aims of the proposal. Career development mechanisms will include instructive seminars and mentored guidance in grant writing, academic job interviewing, laboratory management, and manuscript preparation. An advisory committee will evaluate the completion of both my scientific and career development milestones and facilitate my transition into an independent investigator. Tissue engineering approaches for the urinary bladder have recently been developed utilizing 3D scaffolds seeded with autologous smooth muscle cells (SMCs). These strategies have led to partial restoration of organ functionality in short-term clinical trials. However, the efficacy of these constructs for complete defect repair may be limited by the suboptimal properties of conventional biomaterial carriers and availability of functionally competent cell sources. Silk-based biomaterials provide an exceptional combination of physical characteristics that are well suited to support bladder function and therefore may address limitations associated with current scaffold materials. Pluripotent stem cell populations such as embryonic stem cells (ESCs) and/or induced pluripotent stem (iPS) cells may fulfill the need for alternative cell sources capable of generating organ and patient-specific SMCs. In order to address the current limitations in bladder functional tissue engineering (FTE), we will challenge the overall hypothesis that: FTE modalities using silk-based biomaterials seeded with primary or stem cell-derived SMCs will promote smooth muscle defect consolidation and restoration of bladder function. The specific aims of the study are: Aim 1: Determine the efficacy of silk-based biomaterials seeded with primary SMCs for bladder smooth muscle tissue regeneration. Aim 2: Evaluate the utility of ESC and iPS-derived SMCs as cell sources for functional bladder tissue engineering.

项目摘要/摘要 我在此提案中的总体目标是解决膀胱手术选项的当前限制 重建我的专业能力，使其过渡到独立调查员。我的 专业目标是在一家出色的学术机构中担任实验室主任，这将使我 通过创建创新的基于干细胞的疗法，继续扩大再生医学的前沿 用于泌尿外科组织的重建。我的主要研究培训目标是获得新的技术 泌尿外科组织工程系统和人类多能干细胞生物学的技能。这将是 通过其他基本课程和实验室协议的指导来完成 提案的目的中详细介绍了技术。职业发展机制将包括启发性 研讨会和指导的指导授予写作，学术工作面试，实验室管理以及 手稿准备。咨询委员会将评估我的科学和职业的完成 发展里程碑，并促进我向独立研究者的过渡。 最近已经开发了用于膀胱的组织工程方法 3D脚手架，用自体平滑肌细胞（SMC）播种。这些策略导致了部分 在短期临床试验中恢复器官功能。但是，这些结构的功效 完全的缺陷维修可能受到常规生物材料载体和 功能胜任的细胞来源的可用性。基于丝绸的生物材料提供了特殊的 非常适合支持膀胱功能的物理特征的组合，因此可能 地址与当前脚手架材料相关的限制。多能干细胞种群，例如 胚胎干细胞（ESC）和/或诱导的多能茎（IPS）细胞可能满足对 能够产生器官和患者特异性SMC的替代细胞源。为了解决 膀胱功能组织工程（FTE）的当前局限性，我们将挑战以下总体假设： 使用基于丝绸或干细胞衍生的SMC的丝绸基材料的FTE模式将促进 平滑肌缺陷巩固和膀胱功能的恢复。研究的具体目的 是：目标1：确定用主要SMC接种丝绸的丝基生物材料的功效 平滑肌组织再生。 AIM 2：评估ESC和IPS衍生的SMC的效用为单元 功能性膀胱组织工程的来源。