Osteogenic Enrichment of Adipose Derived Stromal Cells

脂肪源性基质细胞的成骨富集

• 批准号: 8908895
• 负责人: GEOFFREY C GURTNER
• 金额: $ 39.5万
• 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 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8908895
• 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; Heterogeneity; Human; In Vitro; Incidence; Individual; Infection; Injury; Laboratories; Life; Mesenchymal; Methods; 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; Science; 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; mature animal; novel; osteogenic; osteoprogenitor cell; prospective; public health relevance; 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，人类脂肪来源的基质细胞（hASCs）在颅面骨骼再生中具有未来的应用前景。与骨髓间充质细胞相比，人类ASCs很容易通过简单的吸脂程序获得，并且易于扩展。此外，人类ASCs经历快速成骨分化。在我们的实验室中，我们令人信服地观察到，无论是来自小鼠还是人类的ASCs，都有助于小鼠颅骨缺损的骨愈合。例如，在小鼠顶骨（直径4mm）的手术缺陷中，即使在受伤后16周，未经治疗也没有愈合。在骨导电性支架直接应用hASC后，在损伤后4周内观察到明显的骨愈合。也许最令人兴奋的是hasc在人类病人身上的应用。在小规模的初步研究中，头盖骨、上颌骨和下颌骨的缺陷已经愈合，或者使用hASCs能够更快地愈合。然而，目前对ASC身份和功能的了解仍然不足以进行更大规模的临床试验和应用，因为它们是一个高度异质性的细胞群。虽然表面抗原表达是这种理解的重要组成部分，但可能需要更深入的分析来充分表征hASCs。我们的目标是通过完成本提案中描述的具体目标来提供这种分析。我们期望这些研究的结果通过提供对hASCs转录多样性的新理解来推动该领域的发展。我们预计，我们的创新方法的发现将有助于在单细胞水平上定义转录活性和细胞表面标记物之间的关系。这种理解将使我们能够更有针对性地丰富颅面骨骼再生的理想细胞群。