Engineered Delivery of Adult Versus Fetal Stem Cells for Bone Regeneration

描述（由申请人提供）：胎儿组织的强大再生潜力表明，发育生物学可能有助于指导成人组织再生的策略。子宫后再生能力的下降和年龄的增加可能是由于多种因素，然而，一个重要的贡献者可能是负责对损伤进行修复反应的干细胞的可用性和功能的变化。该生物工程研究伙伴关系的总体目标是表征和定量比较从人类发育的两个不同阶段（胎儿和成人）分离的干细胞的相对再生能力，并评估不同策略提供干细胞用于骨再生的有效性。本研究的核心假设是，增加损伤部位的活干细胞数量并促进其修复表型将以发育阶段依赖性方式显著增强骨缺损和脊柱融合的功能修复。为了验证这一假设，多学科团队将把干细胞生物学与组织工程原理和成熟的定量测试床模型相结合。该方法将采用定制的基因阵列分析来阐明来自羊水和成人骨髓的干细胞在基线和成骨分化期间的差异基因调控途径。将评价复合支架和生物补片技术有效输送干细胞用于节段性缺损修复和脊柱融合的能力。最后，一种新型的仿生涂层技术将被研究作为一种手段，以程序交付的干细胞向成骨表型。这项研究的独特之处在于，以前很少有研究定量比较不同干细胞来源的再生能力，特别是来自不同发育阶段的干细胞。这些研究的预期结果是鉴定有效的干细胞来源和递送方案，其可快速转化为缺乏足够内源性细胞修复机制的患者的新治疗选择。公共卫生相关性：受伤或退化的肌肉骨骼组织是世界范围内长期疼痛和残疾的最常见原因，促使人们努力开发新的组织再生疗法。使用新的细胞递送方法，该项目将定量比较来自不同发育阶段（胎儿和成人）的两种非胚胎干细胞来源在大骨缺损和脊柱融合的临床相关环境中的再生能力。

DESCRIPTION (provided by applicant): The robust regeneration potential of fetal tissue suggests that developmental biology may help guide strategies for tissue regeneration in adults. Decreases in regenerative capacity post-utero and with increasing age are likely due to multiple factors, however one important contributor may be changes in the availability and functionality of stem cells responsible for mounting a reparative response to injury. The overall objectives of this Bioengineering Research Partnership are to characterize and quantitatively compare the relative regenerative capacity of stem cells isolated from two distinct stages of human development (fetal and adult) and assess the effectiveness of different strategies for delivering stem cells for bone regeneration. The central hypothesis governing this research is that augmenting the number of viable stem cells at the injury site and promoting their reparative phenotype will significantly enhance functional repair of bone defects and spine fusion in a developmental stage dependent manner. To test this hypothesis, the multidisciplinary team will integrate stem cell biology with tissue engineering principles and well-established, quantitative test bed models. The approach will employ customized gene array analysis to elucidate differential gene regulation pathways of stem cells derived from amniotic fluid and adult bone marrow at baseline and during osteogenic differentiation. Composite scaffold and nanofiber mesh biomaterials technologies will be evaluated for their ability to effectively deliver stem cells for segmental defect repair and spine fusion. Finally, a novel biomimetic coating technology will be investigated as a means to program delivered stem cells towards the osteogenic phenotype. The proposed research is unique in that there has been very little to no previous research on quantitatively comparing the regenerative capacity of different stem cell sources, particularly from distinct developmental stages. The expected outcome of these studies is the identification of an effective stem cell source and delivery protocol that may be rapidly translated into new therapeutic options for patients lacking adequate endogenous cell repair mechanisms. PUBLIC HEALTH RELEVANCE: Injured or degenerated musculoskeletal tissues are the most common cause of long-term pain and disability world-wide, motivating efforts to develop new tissue regenerative therapies. Using novel cell delivery approaches, this project will quantitatively compare the regenerative capacity of two non-embryonic stem cell sources from different developmental stages (fetal and adult) in the clinically relevant settings of large bone defects and spine fusion.