Cellular Remodeling of ECM Scaffolds

ECM 支架的细胞重塑

• 批准号: 7574576
• 负责人: Stephen F. Badylak
• 金额: $ 31.18万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7574576
• 关键词: Address; Angiogenic Peptides; Animals; Antigen Presentation; Binding; Biology; Blood Vessels; Bone Marrow; Bone Marrow Cells; Bone Marrow Involvement; Cardiovascular system; Cell Lineage; Cell-Matrix Junction; Cells; Chemicals; Chemotactic Factors; Cicatrix; Clinical; Collagen; Complement; Deposition; Development; Dura Mater; Esophagus; Extracellular Matrix; Extracellular Matrix Degradation; Fibroblast Growth Factor; Fibroblast Growth Factor 2; Fibroblasts; Growth Factor; Hematopoietic; Hematopoietic stem cells; Heparitin Sulfate; Human; Inflammatory Response; Laboratories; Laminin; Ligands; Location; Lower urinary tract; Marrow; Mediating; Medicine; Modeling; Natural regeneration; Operative Surgical Procedures; Pattern; Peptides; Play; Population; Principal Investigator; Process; Property; Recruitment Activity; Regenerative Medicine; Relative (related person); Research Personnel; Rodent Model; Role; Signal Transduction; Site; Skin; Source; Stem Cell Development; Stem cells; Structure; Subcutaneous Tissue; Testing; Thick; Time; TimeLine; Tissue Engineering; Tissues; Transgenic Mice; Vascular Endothelial Cell; Work; Wound Healing; achilles tendon; angiogenesis; base; cell motility; clinical application; crosslink; implantation; in vivo; injured; migration; mouse model; neovascularization; pre-clinical; precursor cell; programs; reconstruction; repaired; scaffold; self assembly; soft tissue; stem cell biology; tissue reconstruction; transdifferentiation

DESCRIPTION (provided by applicant): Biologic scaffolds composed of extracellular matrix (ECM) have been successfully used as inductive templates for the constructive remodeling of many tissues including the lower urinary tract, skin, musculotendinous tissues and esophagus, among others in both preclinical animal studies and in human clinical applications. However, the mechanisms by which this constructive remodeling process occurs in diverse tissues is largely unknown. The source of cells that populate and participate in the ECM remodeling process is a source of controversy and the ability to control such a cell population would represent a significant technical advance in the field of regenerative medicine. The proposed work will address a very focused aspect of the cellular remodeling process. Specifically, we will examine the temporal and spatial patterns of ECM remodeling by two populations of cells: ciculating fibrocytes and local tissue fibroblasts. Circulating fibrocytes are a population of marrow derived cells of hematopoietic origin that have been shown to participate in wound healing, angiogenesis, antigen presentation, and tissue remodeling. To date, these cells have not been examined for their role in tissue reconstruction with an ECM based scaffold approach. We will examine both the bone marrow and surrounding soft tissue as potential sources of both circulating fibrocytes and local tissue fibroblasts during the remodeling process. Using chimeric and transgenic mouse models we will track selected cell populations during studies to accomplish two specific aims. The first specific aim will determine the involvement of bone marrow derived fibrocytes in the remodeling process of ECM biologic scaffolds. The second specific aim will determine the role of local tissue fibroblasts in the remodeling process. We have assembled a highly interdisciplinary team with expertise in medicine, surgery, tissue engineering, ECM biology, stem cell biology, and cellular differentiation. We have identified clearly defined specific aims with quantifiable end points and an efficient three year timeline to conduct this work.

描述（由申请人提供）：在临床前动物研究和人类临床应用中，由细胞外基质（ECM）组成的生物支架已成功用作许多组织（包括下尿路、皮肤、肌腱组织和食管）的结构性重塑的诱导模板。然而，这种结构性重塑过程在不同组织中发生的机制在很大程度上是未知的。填充并参与ECM重塑过程的细胞的来源是争议的来源，并且控制这样的细胞群体的能力将代表再生医学领域的重大技术进步。拟议的工作将解决一个非常集中的方面的细胞重塑过程。具体来说，我们将研究ECM重塑的时间和空间模式的两个群体的细胞：循环纤维细胞和局部组织成纤维细胞。循环纤维细胞是造血来源的骨髓源性细胞群，其已显示参与伤口愈合、血管生成、抗原呈递和组织重塑。到目前为止，这些细胞还没有被检查其在组织重建与ECM为基础的支架方法的作用。我们将检查骨髓和周围软组织作为重塑过程中循环纤维细胞和局部组织成纤维细胞的潜在来源。使用嵌合和转基因小鼠模型，我们将在研究过程中跟踪选定的细胞群，以实现两个特定的目标。第一个具体目标将确定骨髓来源的纤维细胞参与ECM生物支架的重塑过程。第二个具体目标将确定局部组织成纤维细胞在重塑过程中的作用。我们组建了一支高度跨学科的团队，拥有医学，外科，组织工程，ECM生物学，干细胞生物学和细胞分化方面的专业知识。我们已经确定了明确定义的具体目标，可量化的终点和有效的三年时间轴来开展这项工作。

项目成果

Surface characterization of extracellular matrix scaffolds.

• DOI: 10.1016/j.biomaterials.2009.09.061
• 发表时间: 2010-01
• 期刊: BIOMATERIALS
• 影响因子: 14
• 作者: Brown, Bryan N.;Barnes, Christopher A.;Kasick, Rena T.;Michel, Roger;Gilbert, Thomas W.;Beer-Stolz, Donna;Castner, David G.;Ratner, BuddyD.;Badylak, Stephen F.
• 通讯作者: Badylak, Stephen F.

The effects of processing methods upon mechanical and biologic properties of porcine dermal extracellular matrix scaffolds.

• DOI: 10.1016/j.biomaterials.2010.07.083
• 发表时间: 2010-11
• 期刊: BIOMATERIALS
• 影响因子: 14
• 作者: Reing, Janet E.;Brown, Bryan N.;Daly, Kerry A.;Freund, John M.;Gilbert, Thomas W.;Hsiong, Susan X.;Huber, Alexander;Kullas, Karen E.;Tottey, Stephen;Wolf, Matthew T.;Badylak, Stephen F.
• 通讯作者: Badylak, Stephen F.

Macrophage phenotype as a predictor of constructive remodeling following the implantation of biologically derived surgical mesh materials.

• DOI: 10.1016/j.actbio.2011.11.031
• 发表时间: 2012-03
• 期刊: ACTA BIOMATERIALIA
• 影响因子: 9.7
• 作者: Brown, Bryan N.;Londono, Ricardo;Tottey, Stephen;Zhang, Li;Kukla, Kathryn A.;Wolf, Matthew T.;Daly, Kerry A.;Reing, Janet E.;Badylak, Stephen F.
• 通讯作者: Badylak, Stephen F.

Evidence of innervation following extracellular matrix scaffold-mediated remodelling of muscular tissues.

• DOI: 10.1002/term.200
• 发表时间: 2009-12
• 期刊: JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE
• 影响因子: 3.3
• 作者: Agrawal, Vineet;Brown, Bryan N.;Beattie, Allison J.;Gilbert, Thomas W.;Badylak, Stephen F.
• 通讯作者: Badylak, Stephen F.

Mechanical characterization of adult stem cells from bone marrow and perivascular niches.

• DOI: 10.1016/j.jbiomech.2012.01.032
• 发表时间: 2012-04-30
• 期刊: Journal of biomechanics
• 影响因子: 2.4
• 作者: Ribeiro AJ;Tottey S;Taylor RW;Bise R;Kanade T;Badylak SF;Dahl KN
• 通讯作者: Dahl KN