Stromal Stem Cells of Human Placenta for the Treatment of Acute Lung Injury

人胎盘基质干细胞治疗急性肺损伤

• 批准号: 8518446
• 负责人: Fernando Viteri
• 金额: $ 18.24万
• 依托单位: PLASALUS, LLC
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8518446
• 关键词: Acute Disease; Acute Lung Injury; Acute respiratory failure; Address; Adult; Alveolar; Angiopoietins; Animal Model; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Bone Marrow; Cell Line; Cell Therapy; Cell physiology; Cell secretion; Cells; Characteristics; Chorion; Cicatrix; Critical Illness; Data; Development; Effectiveness; Endothelium; Endotoxins; Engraftment; Enzyme-Linked Immunosorbent Assay; Epithelial; Epithelium; Escherichia coli; Fetal Tissues; Fibroblast Growth Factor; Fibrosis; Future; Granulocyte-Macrophage Colony-Stimulating Factor; Growth; Growth Factor; Hematopoietic; Human; Infection; Inflammatory; Injury; Investigation; Knowledge; Liquid substance; Lung; Measures; Mediating; Mesenchymal; Mesenchymal Stem Cells; Mesenchyme; Modeling; Morphology; Mus; Nature; Organ; Outcome; Paracrine Communication; Patients; Phenotype; Placenta; Preparation; Production; Pulmonary Edema; Regenerative Medicine; Research; Source; Stem cells; Stromal Cells; Testing; Therapeutic; Therapeutic Use Study; Therapeutic Uses; Time; Transforming Growth Factor beta; Treatment Effectiveness; Treatment Efficacy; Type II Epithelial Receptor Cell; United States National Institutes of Health; base; blastomere structure; cell type; clinically relevant; cost; cytokine; fetal; fetal stem cell; human embryonic stem cell; human stem cells; improved; injured; lung development; lung injury; mouse model; novel; paracrine; placental stem cell; potency testing; programs; public health relevance; repaired; restoration; tissue regeneration

DESCRIPTION (provided by applicant): There is a need for new sources of multipotent, highly therapeutically effective, patient-specific stem cells. The placenta is a novel potential source of fetal stem cells. Studies of therapeutic use involving placental stem cells have not been conducted. We plan to address this need by accomplishing a research program with support from the NIH that will enable us to develop a therapeutic product utilizing selected placental stromal cells for the treatment of Acute Lung Injury. Acute Lung Injury is a major cause of acute respiratory failure in critically ill patients which requires development of novel modes of therapy This project will further contribute to the advances in knowledge of stem cell function and to the potential for regenerative medicine using stem cells derived from the placenta. Our hypothesis is that the chorion of human placenta contains large numbers of mesenchymal stem cells, which release several beneficial paracrine factors. This hypothesis is based on our recent discoveries that human placenta is a hematopoietic organ and term placenta is a niche of abundant numbers of hematopoietic cells. Other cells, sharing the phenotype of stromal cells and embryonic cells are present in the mesenchyme of human placental chorion. These cells are highly active in paracrine signaling and secrete abundant quantities of growth factors like HGF, KGF, TGF-beta, FGF, GM-CSF, and angiopoietins. Stromal cells from the placenta are effective in restoration of barrier function of injured epithelial layers. In Specific Aim 1, we will test th multipotency of mesenchymal chorionic cells derived from human placenta and their high paracrine activity. We will generate chorionic mesenchymal cell lines and characterize their proliferation and differentiation potential. Cells will be characterized by their morphology, abiliy to propagate in culture, expression of markers of human embryonic stem cells (SSEA-3, Oct-4, TRA-1-60), and embryoid body formation. We will also measure the paracrine activity of cells by ELISA. Cells for therapy will be selected from 20 placentas upon the levels of secretion of HGF, FGF, TGF-beta, GM-CSF, and angiopoietins. In Specific Aim 2, we will test the potential therapeutic value of selected placental stromal stem cells for their efficacy in animal and human lung models of acute lung injury. Cells will be tested for treatment of mice with acute lung injury and for development of lung fibrosis. Placental cells will be further investigated for their effectiveness in facilitation of repair of injured lung epithelium and endothelium in an ex vivo perfused human lung preparation. This project will provide abundant, non-controversial and inexpensive source of therapeutically active stromal stem cells, available for use in humans within a very short period of time (2-4 years).

描述(由申请人提供)：需要新的多潜能、高度治疗有效的、患者特有的干细胞来源。胎盘是一种新的潜在来源 胎儿干细胞。涉及胎盘干细胞的治疗用途的研究尚未进行。我们计划通过在美国国立卫生研究院的支持下完成一项研究计划来满足这一需求，该计划将使我们能够开发一种利用选定的胎盘基质细胞治疗急性肺损伤的治疗产品。急性肺损伤是重症患者急性呼吸衰竭的主要原因，需要开发新的治疗模式。该项目将进一步促进干细胞功能知识的进步，并促进使用来自胎盘的干细胞进行再生医学的可能性。我们的假设是，人胎盘的绒毛膜含有大量的间充质干细胞，它们释放出几种有益的旁分泌因子。这一假说是基于我们最近的发现，即人类胎盘是一个造血器官，而胎盘是一个含有大量造血细胞的利基市场。人胎盘绒毛膜间充质中存在与基质细胞和胚胎细胞表型相同的其他细胞。这些细胞在旁分泌信号中高度活跃，并分泌大量的生长因子，如HGF、KGF、转化生长因子-β、成纤维细胞生长因子、GM-CSF和血管生成素。胎盘基质细胞可有效修复受损上皮层的屏障功能。在具体目标1中，我们将检测人胎盘来源的间充质绒毛细胞的多能性及其高旁分泌活性。我们将建立绒毛膜间充质细胞系，并对其增殖和分化潜能进行鉴定。细胞的特征将包括其形态、在培养中增殖的能力、人类胚胎干细胞标志(SSEA-3、OCT-4、TRA-1-60)的表达以及类胚体的形成。采用酶联免疫吸附试验检测细胞旁分泌活性。治疗细胞将从20个胎盘中根据HGF、FGF、TGF-β、GM-CSF和血管生成素的分泌水平而选择。在特定的目标2中，我们将测试选定的胎盘基质干细胞在动物和人类急性肺损伤模型中的潜在治疗价值。细胞将被用于治疗急性肺损伤的小鼠 并对肺纤维化的发展起到促进作用。在体外灌流的人肺制剂中，胎盘细胞在促进受损的肺上皮和内皮修复方面的有效性将被进一步研究。该项目将提供丰富、无争议和廉价的治疗活性基质干细胞来源，在非常短的时间内(2-4年)可用于人类。