Osteogenic Enrichment of Adipose Derived Stromal Cells

脂肪源性基质细胞的成骨富集

• 批准号: 9127188
• 负责人: GEOFFREY C GURTNER
• 金额: $ 39.51万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-03 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9127188
• 关键词: Address; Adipose tissue; Adult; Age; Bioinformatics; Biomedical Engineering; Bone Marrow; Bone Tissue; Caliber; Calvaria; Case Study; Cell Separation; Cell Surface Receptors; Cell surface; Cells; Cellular biology; Cephalic; Child; Clinical Research; Clinical Trials; Complementary DNA; Complex; Computer Analysis; Craniofacial Abnormalities; Data; Defect; Developmental Biology; Disease; Effectiveness; Etiology; Future; Gene Expression; Gene Expression Profile; Gene Targeting; Genes; Genetic Transcription; Growth; Harvest; Healed; Health; Heterogeneity; Human; In Vitro; Incidence; Individual; Infection; Injury; Laboratories; Life; Mesenchymal; Methods; Microfluidic Microchips; Microfluidics; Molecular Profiling; Mus; Musculoskeletal System; Operative Surgical Procedures; Organogenesis; Osteogenesis; Parietal bone structure; Patients; Pilot Projects; Population; Population Heterogeneity; Procedures; Reaction; Reagent; Regenerative Medicine; Resolution; Reverse Transcriptase Polymerase Chain Reaction; Risk; Stem cells; Stromal Cells; Subgroup; Suction Lipectomy; Surface Antigens; Surgeon; Techniques; Therapeutic; Tissue Engineering; Tissues; base; bone; clinical application; cost; craniofacial; cranium; healing; immature animal; improved; in vivo; innovation; interest; mandible/maxilla; materials science; mature animal; novel; osteogenic; osteoprogenitor cell; prospective; reconstruction; regenerative; repaired; response; scaffold; skeletal; skeletal regeneration; stem; stem cell biology; tissue regeneration; tissue repair

DESCRIPTION (provided by applicant): Multiple lines of evidence suggest that human adipose-derived stromal cells (hASCs) hold promise for future use in craniofacial skeletal regeneration. Human ASCs are easily harvested by simple liposuction procedures and are readily expandable as compared to bone marrow mesenchymal cells. Moreover, human ASCs undergo rapid osteogenic differentiation. In our laboratory, we have observed convincingly that ASCs, whether derived from mouse or human origin, contribute to osseous healing of mouse calvarial defects. For example, a surgical defect in the mouse parietal bone (4mm in diameter) shows no healing when untreated even up to 16 weeks post injury. Upon direct hASC application with an osteoconductive scaffold, significant bony healing is observed in as little as 4 weeks post injury. Perhaps most exciting are those applications of hASCs to the human patient. In small pilot studies, defects of the cranium, maxilla, and mandible have been either healed or enabled to heal faster with the use of hASCs. The current understanding of ASC identity and function, however, remains insufficient to allow larger clinical trials and applications as they are a highly heterogeneous population of cells. While surface antigen expression is an important component to this understanding, it is likely that more in depth analysis will be required to fully characterize hASCs. We aim to provide this analysis through completion of the Specific Aims described in this proposal. We expect the results of these studies to move the field forward by providing a new understanding of the transcriptional diversity within hASCs. We anticipate that the findings from our innovative approach will help to define the relationship between transcriptional activity and cell surface markers on a single cell level. This understanding will allow us to more specifically enrich for a population of cells ideal for craniofacial skeletal regeneration.

描述（由申请人提供）：多种证据表明，人脂肪衍生的基质细胞（HASC）有望在颅面骨骼再生中使用未来。与骨髓间充质细胞相比，通过简单的吸脂手术很容易收获人类ASC。此外，人类ASC经历了快速的成骨分化。在我们的实验室中，我们令人信服地观察到，无论是源自小鼠还是人类来源，ASC都会导致小鼠颅骨缺陷的骨愈合。例如，小鼠顶骨（直径为4mm）中的手术缺陷在受伤后至16周没有治疗时没有愈合。直接施用带有整骨支架的HASC时，在受伤后短短4周内观察到明显的骨愈合。也许最令人兴奋的是HASC对人类患者的应用。在小型试点研究中，颅骨，上颌骨和下颌骨的缺陷已被治愈或可以通过使用HASC来更快地治愈。然而，目前对ASC身份和功能的理解仍然不足以允许更大的临床试验和应用，因为它们是高度异质的细胞群体。尽管表面抗原表达是这种理解的重要组成部分，但可能需要更多的深度分析才能充分表征HASC。我们旨在通过完成本提案中描述的具体目的来提供此分析。我们希望这些研究的结果通过对HASC中的转录多样性有了新的了解来推动该领域的前进。我们预计我们创新方法的发现将有助于定义单个细胞水平上转录活性与细胞表面标记之间的关系。这种理解将使我们能够更具体地为颅面骨骼再生的理想的细胞群体丰富。

项目成果

Magnetic Nanoparticle-Based Upregulation of B-Cell Lymphoma 2 Enhances Bone Regeneration.

• DOI: 10.5966/sctm.2016-0051
• 发表时间: 2017-01
• 期刊: Stem cells translational medicine
• 影响因子: 6
• 作者: Brett E;Zielins ER;Luan A;Ooi CC;Shailendra S;Atashroo D;Menon S;Blackshear C;Flacco J;Quarto N;Wang SX;Longaker MT;Wan DC
• 通讯作者: Wan DC

Stem and progenitor cells: advancing bone tissue engineering.

• DOI: 10.1007/s13346-015-0235-1
• 发表时间: 2016-04
• 期刊: Drug delivery and translational research
• 影响因子: 5.4
• 作者: Tevlin R;Walmsley GG;Marecic O;Hu MS;Wan DC;Longaker MT
• 通讯作者: Longaker MT

Commentary on the differential healing capacity of calvarial bone.

颅骨愈合能力差异的评论。

• DOI: 10.1097/scs.0b013e3182802256
• 发表时间: 2013
• 期刊: The Journal of craniofacial surgery
• 作者: Lo,DavidD;McArdle,Adrian;Senarath-Yapa,Kshemendra;Longaker,MichaelT
• 通讯作者: Longaker,MichaelT

The role of stem cells in limb regeneration.

干细胞在肢体再生中的作用。

• DOI: 10.1080/15476278.2016.1163463
• 发表时间: 2016
• 期刊: Organogenesis
• 影响因子: 2.3
• 作者: Zielins,ElizabethR;Ransom,RyanC;Leavitt,TrippE;Longaker,MichaelT;Wan,DerrickC
• 通讯作者: Wan,DerrickC

Enhanced Activation of Canonical Wnt Signaling Confers Mesoderm-Derived Parietal Bone with Similar Osteogenic and Skeletal Healing Capacity to Neural Crest-Derived Frontal Bone.

• DOI: 10.1371/journal.pone.0138059
• 发表时间: 2015
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Li S;Quarto N;Senarath-Yapa K;Grey N;Bai X;Longaker MT
• 通讯作者: Longaker MT