Stem Cell Morphogen Delivery via Engineered Biomaterials

通过工程生物材料输送干细胞形态原

• 批准号: 8334391
• 负责人: Todd C McDevitt
• 金额: $ 37.63万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-16 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8334391
• 关键词: Address; Adult; Binding; Biocompatible Materials; Biology; Cell Survival; Cell Therapy; Cells; Cellularity; Chronic; Complex; Defect; Degenerative Disorder; Dermal; Development; Developmental Biology; Disease; Dose; Embryo; Engineering; Engraftment; Environment; Evaluation; Extracellular Matrix; Extracellular Matrix Proteins; Fetal Development; Fright; General Population; Glycosaminoglycans; Goals; Growth Factor; Hindlimb; In Vitro; Individual; Injury; Label; Laboratories; Lead; Mammals; Mediating; Methods; Modification; Molecular; Morphogenesis; Mus; Natural regeneration; Normal tissue morphology; Phenotype; Pluripotent Stem Cells; Population; Process; Rattus; Regenerative Medicine; Research Personnel; Retrieval; Safety; Signal Transduction; Site; Staging; Stem cell transplant; Stem cells; Structure; Therapeutic; Time; Tissues; Translating; Transplantation; Work; Wound Healing; base; bone; cell type; chemical synthesis; embryonic stem cell; engineering design; extracellular; functional improvement; improved; in vivo; injured; insight; interest; mimetics; morphogens; multidisciplinary; paracrine; regenerative; stem cell differentiation; stem cell population; stem cell therapy; tissue regeneration; tissue repair; trait; tumorigenic; wound

DESCRIPTION (provided by applicant): Functional tissue regeneration remains an elusive goal for the treatment of a variety of traumatic injuries and chronic degenerative diseases that afflict a significant portion of the general population. Although mammals successfully regenerate tissues during early stages of fetal development, this trait is irreversibly lost as mammals mature. The contrast between embryonic and adult wound healing mechanisms suggests that the microenvironment that facilitates proper tissue regeneration in embryos is distinctly different from that of adult somatic tissues. Therefore, obtaining and introducing the molecular constituents of embryonic microenvironments to sites of adult tissue injury or disease may alter the course of endogenous tissue repair, yielding functional neo-tissues. A number of stem cell therapies are being developed in an attempt to restore the cellularity of damaged tissues, and in most instances, despite low levels of engraftment and differentiation into mature cell types, transplanted stem cells evoke significant functional improvements in the regenerative potential of tissues, indicating that the factors produced by stem cells may in fact directly impact tissue morphogenesis. This concept suggests a potential paradigm shift in the development and application of regenerative stem cell therapies - from cell replacement substitutes to biocatalytic agents of tissue regeneration. Thus, the objective of this proposal is to develop engineered biomaterials capable of sequestering morphogenic factors produced by differentiating embryonic stem cells (ESCs) and to deliver ESC-derived morphogens to adult wound sites in order to enhance tissue regeneration. These studies will provide new insights into the regenerative function of pluripotent stem cells and mechanisms of mammalian tissue repair, as well as directly lead to the development of a new class of regenerative molecular therapeutics to treat a variety of traumatic injuries and degenerative diseases.

描述（由申请人提供）：功能性组织再生仍然是一个难以实现的目标，用于治疗各种创伤性损伤和慢性退行性疾病，这些疾病困扰着相当一部分普通人群。虽然哺乳动物在胎儿发育的早期阶段成功地再生组织，但随着哺乳动物的成熟，这种特征不可逆转地消失了。胚胎和成人伤口愈合机制之间的对比表明，促进胚胎适当组织再生的微环境与成人体组织的微环境明显不同。因此，获得胚胎微环境的分子成分并将其引入成人组织损伤或疾病的部位可能会改变内源性组织修复的过程，产生功能性新组织。许多干细胞疗法正在开发中，试图恢复受损组织的细胞性，并且在大多数情况下，尽管移植和分化成成熟细胞类型的水平较低，但移植的干细胞引起组织再生潜力的显著功能改善，表明干细胞产生的因子实际上可能直接影响组织形态发生。这一概念表明再生干细胞疗法的开发和应用的潜在范式转变-从细胞替代替代品到组织再生的生物催化剂。因此，本提案的目的是开发能够隔离由分化的胚胎干细胞（ESC）产生的形态发生因子的工程生物材料，并将ESC衍生的形态发生因子递送至成人伤口部位以增强组织再生。这些研究将为多能干细胞的再生功能和哺乳动物组织修复机制提供新的见解，并直接导致一类新的再生分子疗法的发展，以治疗各种创伤性损伤和退行性疾病。