Stem Cell Integral Membrane Transporter ABCB5 and Dermal Regeneration

干细胞整体膜转运蛋白 ABCB5 和真皮再生

• 批准号: 10494660
• 负责人: Markus H. Frank
• 金额: $ 58万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-30 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10494660
• 关键词: Address; Adult; Age; Age-Years; Aging; Allogenic; Animal Model; Anti-Inflammatory Agents; Autologous; Binding; Biology of Aging; Cell Compartmentation; Cell Differentiation process; Cell Maintenance; Cell Therapy; Cell membrane; Cell surface; Cells; Chronic; Clinical Trials; Data; Dermal; Dermis; Development; Disease; Documentation; Elasticity; Employment; Epidermis; Epigenetic Process; Family member; Foundations; Frequencies; Functional disorder; Genetic; Germany; Hair; Health; Homeostasis; Human; Immune; Impaired wound healing; Impairment; Inflammaging; Institutes; Investigation; Knockout Mice; Membrane Proteins; Membrane Transport Proteins; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Modeling; Molecular; Mus; Natural regeneration; Organism; Pathway interactions; Patients; Pharmaceutical Preparations; Prevention; Prospective Studies; Receptor Protein-Tyrosine Kinases; Regenerative Medicine; Regenerative capacity; Research; Role; Signal Pathway; Signal Transduction; Skin; Skin Aging; Skin injury; Somatic Cell; Stem cell transplant; Testing; Therapeutic; Tissue Differentiation; Varicose Ulcer; Venous Insufficiency; adult stem cell; age related; angiogenesis; appendage; base; chronic wound; experimental study; immunoregulation; mouse model; non-healing wounds; novel; older patient; pre-clinical; rational design; regenerative; regenerative tissue; repaired; self-renewal; skin disorder; skin regeneration; skin wound; stem cell aging; stem cell biology; stem cell population; stem cells; tongue papilla; translational impact; translational potential; vasculogenesis; wound; wound healing

PROJECT SUMMARY Project 3 will test the central hypotheses that (1) ABCB5(+) dermal mesenchymal stem cells (DMSC) are required for normal adult skin homeostasis and regeneration; (2) ABCB5(+) DMSC decline is responsible for impaired skin homeostasis and regenerative wound healing during aging; and (3) ABCB5(+) DMSC transplantation possesses therapeutic potential to restore age-related impairment of skin homeostasis and regeneration. The overall significance of this study are the potential shifts in research paradigms resulting from successful completion of this research: (1) The proposed experiments will answer a fundamental question in stem cell biology and aging that has not been addressed as-of-yet in prospective studies – To what extent is selective dysfunction in an adult stem cell compartment (vis-à-vis dysregulation of differentiated tissues) responsible for organismal aging?; and (2) Documentation of the regenerative capacity of ABCB5(+) DMSC along with demonstration of their decline as a cause age-related impairment of skin regenerative capacity will lay the foundation for targeted employment of this candidate cell therapeutic for the treatment of cutaneous wounds in aging patients.

项目摘要 项目3将测试以下中心假设：（1）ABCB 5（+）真皮间充质干细胞（DMSC）是 正常成人皮肤稳态和再生所需;（2）ABCB 5（+）DMSC下降负责 用于老化期间受损的皮肤稳态和再生伤口愈合;和（3）ABCB 5（+）DMSC 移植具有恢复与年龄相关的皮肤稳态损伤的治疗潜力， 再生这项研究的总体意义是研究范式的潜在转变， 从成功完成这项研究：（1）拟议的实验将回答一个基本的 干细胞生物学和衰老的问题，尚未解决的前瞻性研究- 成体干细胞区室中的选择性功能障碍（维斯于 分化组织）负责有机体老化？（2）记录再生 ABCB 5（+）DMSC的能力沿着其下降是年龄相关性损伤的原因 皮肤再生能力的提高将为有针对性地使用这种候选细胞奠定基础 用于治疗老年患者的皮肤伤口的治疗剂。