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: 8262711
• 负责人: Joshua Robert Mauney
• 金额: $ 8.92万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-15 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8262711
• 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; public health relevance; reconstruction; repaired; research study; restoration; scaffold; skills; stem; stem cell biology; stem cell population; tissue reconstruction; tissue regeneration; urologic

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: The results of this proposal are anticipated to produce new tissue regeneration strategies that will overcome current biomaterial and cell source limitations for urinary bladder reconstruction. This study will provide new information that is wider in scope than our specific goals and which may be applicable for repair of other urogenital tissues (e.g. urethra) and possibly other hollow organs.

描述（由申请人提供）：我在此提案中的总体目标是解决膀胱重建手术选择的当前局限性，同时发展我的专业能力将过渡到独立研究者。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，这将使我能够通过创建基于创新的干细胞疗法来扩大再生医学的前沿。我的主要研究培训目标是在泌尿外科组织系统和人类多能干细胞生物学方面获得新的技术技能。这将通过额外的基本课程以及提案目的详细介绍的实验室协议和技术的指导来实现。职业发展机制将包括启发性研讨会，并在授予写作，学术工作面试，实验室管理和手稿准备方面提供指导。咨询委员会将评估我的科学和职业发展里程碑的完成，并促进我向独立调查员的过渡。 最近，使用了用自体平滑肌细胞（SMC）种子的3D支架（SMC）开发了膀胱的组织工程方法。这些策略导致在短期临床试验中部分恢复器官功能。但是，这些构建体对完全缺陷修复的功效可能受到常规生物材料载体的次优性能以及功能合理的细胞源的可用性的限制。基于丝绸的生物材料提供了非常适合支持膀胱功能的物理特征的特殊特征的特殊组合，因此可以解决与当前脚手架材料相关的局限性。多能干细胞群，例如胚胎干细胞（ESC）和/或诱导的多能干（IPS）细胞可能满足能够产生器官和患者特异性SMC的替代细胞源的需求。为了解决膀胱功能组织工程（FTE）的当前局限性，我们将挑战以下整体假设：使用基于丝绸或干细胞衍生的SMC的丝绸基于基于丝绸的生物材料的FTE模式将促进平滑肌缺陷整合和膀胱功能的恢复。该研究的具体目的是：目标1：确定用一级SMC播种的丝基生物材料对膀胱平滑肌组织再生的功效。 AIM 2：评估ESC和IPS衍生的SMC的效用，作为功能性膀胱组织工程的细胞来源。 公共卫生相关性：预计该提案的结果将产生新的组织再生策略，这些策略将克服当前的生物材料和细胞源限制，以解决膀胱重建。这项研究将提供比我们的特定目标更广泛的新信息，并且可能适用于修复其他泌尿生殖组织（例如尿道）和其他空心器官。