权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Human macrophage immunophenotype modulated by biomaterial-encapsulated MSC

生物材料封装的 MSC 调节人巨噬细胞免疫表型

基本信息

批准号：
8444057
负责人：
WEIYUAN J KAO
金额：
$ 17.52万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-08-01 至 2015-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8444057
关键词：
3-Dimensional Accounting Acute Adult Allogenic Animal Model Anti-Inflammatory Agents Anti-inflammatory Antigen Presentation Beds Biocompatible Materials Biomechanics Blood Bone Marrow Cardiovascular Diseases Cell Fate Control Cell Therapy Cell Transplantation Cell physiology Cells Chemicals Chronic Clinic Clinical Clinical Research Coculture Techniques Collaborations Cutaneous Development Disadvantaged Disease Encapsulated Ethics Event Foreign-Body Reaction Goals Healed Hematopathology Hemostatic function Histocompatibility Testing Human Hydrogels Immune response Immunophenotyping Immunosuppressive Agents Impaired wound healing In Vitro Inflammation Inflammatory Injury Interleukins Knowledge Mediating Mediator of activation protein Mesenchymal Modeling Molecular Myocardial Infarction Pathology Pharmaceutical Preparations Phase Phenotype Platelet-Derived Growth Factor Process Property Proteins Recruitment Activity Refractory Regenerative Medicine Research Role Spinal cord injury Staging Stromal Cells Surface Tissue Engineering Tissues Translating Validation Vascular Endothelial Growth Factors Work Wound Healing age related analytical method base design embryonic stem cell graft vs host disease healing implantation improved in vivo loss of function macrophage monocyte pre-clinical public health relevance stem cell therapy tissue regeneration wound

项目摘要

DESCRIPTION (provided by applicant): Adult tissue-derived mesenchymal stromal cells (MSC) have demonstrated promise in treating various pathologies including myocardial infarction, graft versus host disease and other tissue injuries such refractory wounds. Much of current work on MSC-based therapies consists of the development of cell entrapment matrix to control cell function and fate after implantation. While MSC had shown to have immunomodulatory properties, the impact of the MSC-encapsulated biomatrix on the host macrophage immunophenotype and host foreign body reaction is less clear. We hypothesize that adult, human bone marrow-derived MSC (BM- MSC) that are encapsulated into a 3-D biomaterial will preferentially modulate the polarization of host primary macrophages from a pro-inflammatory state towards a pro-healing and anti-inflammatory phenotype. A clear understanding of this three-way interaction between encapsulated MSC, macrophages, and biomaterial using primary human cells is required for the development of effective MSC-hydrogel strategies in cell-based regenerative medicine. To achieve this, we will: (1) formulate well-characterized biomaterials with improved biomechanic properties including strength and lack of contraction over commercially-available cell-delivery matrices for BM-MSC encapsulation; (2) assess the immunophenotype of blood-derived primary macrophages as modulated by biomaterial-entrapped BM-MSC in 3-D co-cultures; (3) confirm the ability of 3-D biomaterial- entrapped BM-MSC to recruit and modulate macrophage pro-healing phenotype in a wound model.

描述（由申请人提供）：成人组织来源的间充质基质细胞（MSC）已被证明在治疗各种病理学方面具有前景，包括心肌梗塞、移植物抗宿主病和其他组织损伤（例如难治性伤口）。目前基于 MSC 的疗法的大部分工作包括开发细胞捕获基质来控制植入后的细胞功能和命运。虽然 MSC 已显示出具有免疫调节特性，但 MSC 封装的生物基质对宿主巨噬细胞免疫表型和宿主异物反应的影响尚不清楚。我们假设封装在 3D 生物材料中的成人人骨髓来源的 MSC (BM-MSC) 将优先调节宿主原代巨噬细胞的极化，从促炎状态向促愈合和抗炎表型转变。为了在细胞再生医学中开发有效的 MSC-水凝胶策略，需要清楚地了解封装的 MSC、巨噬细胞和使用原代人类细胞的生物材料之间的三向相互作用。为了实现这一目标，我们将：（1）配制具有改进的生物力学特性的特征良好的生物材料，包括与市售的用于 BM-MSC 封装的细胞递送基质相比强度和缺乏收缩； (2) 评估 3D 共培养物中生物材料包埋的 BM-MSC 调节的血源性原代巨噬细胞的免疫表型； (3) 确认 3D 生物材料包埋的 BM-MSC 在伤口模型中招募和调节巨噬细胞促愈合表型的能力。