通过功能性分泌组分析对人脐带血（hUCB）中无限制体细胞干细胞（USSC）的再生表型进行表征。
Characterization of Regenerative Phenotype of Unrestricted Somatic Stem Cells (USSC) from Human Umbilical Cord Blood (hUCB) by Functional Secretome Analysis.
作者信息
Schira Jessica, Falkenberg Heiner, Hendricks Marion, Waldera-Lupa Daniel M, Kögler Gesine, Meyer Helmut E, Müller Hans Werner, Stühler Kai
机构信息
From the ‡Molecular Proteomics Laboratory (MPL), Institute for Molecular Medicine, Heinrich Heine University, Universitätsstr. 1, 40225 Düsseldorf, Germany; §Molecular Neurobiology Laboratory, Department of Neurology, Heinrich Heine University Medical Centre Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany;
From the ‡Molecular Proteomics Laboratory (MPL), Institute for Molecular Medicine, Heinrich Heine University, Universitätsstr. 1, 40225 Düsseldorf, Germany;
出版信息
Mol Cell Proteomics. 2015 Oct;14(10):2630-43. doi: 10.1074/mcp.M115.049312. Epub 2015 Jul 16.
Stem cell transplantation is a promising therapeutic strategy to enhance axonal regeneration after spinal cord injury. Unrestricted somatic stem cells (USSC) isolated from human umbilical cord blood is an attractive stem cell population available at GMP grade without any ethical concerns. It has been shown that USSC transplantation into acute injured rat spinal cords leads to axonal regrowth and significant locomotor recovery, yet lacking cell replacement. Instead, USSC secrete trophic factors enhancing neurite growth of primary cortical neurons in vitro. Here, we applied a functional secretome approach characterizing proteins secreted by USSC for the first time and validated candidate neurite growth promoting factors using primary cortical neurons in vitro. By mass spectrometric analysis and exhaustive bioinformatic interrogation we identified 1156 proteins representing the secretome of USSC. Using Gene Ontology we revealed that USSC secretome contains proteins involved in a number of relevant biological processes of nerve regeneration such as cell adhesion, cell motion, blood vessel formation, cytoskeleton organization and extracellular matrix organization. We found for instance that 31 well-known neurite growth promoting factors like, e.g. neuronal growth regulator 1, NDNF, SPARC, and PEDF span the whole abundance range of USSC secretome. By the means of primary cortical neurons in vitro assays we verified SPARC and PEDF as significantly involved in USSC mediated neurite growth and therewith underline their role in improved locomotor recovery after transplantation. From our data we are convinced that USSC are a valuable tool in regenerative medicine as USSC's secretome contains a comprehensive network of trophic factors supporting nerve regeneration not only by a single process but also maintained its regenerative phenotype by a multitude of relevant biological processes.
干细胞移植是一种很有前景的治疗策略，可促进脊髓损伤后的轴突再生。从人脐带血中分离出的无限制体细胞干细胞（USSC）是一种有吸引力的干细胞群体，可在符合药品生产质量管理规范（GMP）等级下获取，且不存在任何伦理问题。研究表明，将USSC移植到急性损伤的大鼠脊髓中可导致轴突再生和显著的运动功能恢复，但不存在细胞替代现象。相反，USSC可分泌营养因子，在体外促进原代皮质神经元的神经突生长。在此，我们首次应用功能分泌组学方法来表征USSC分泌的蛋白质，并使用原代皮质神经元在体外验证了候选神经突生长促进因子。通过质谱分析和详尽的生物信息学探究，我们鉴定出1156种代表USSC分泌组的蛋白质。使用基因本体论，我们发现USSC分泌组包含参与神经再生许多相关生物学过程的蛋白质，如细胞粘附、细胞运动、血管形成、细胞骨架组织和细胞外基质组织。例如，我们发现31种著名的神经突生长促进因子，如神经生长调节因子1、NDNF、SPARC和PEDF，涵盖了USSC分泌组的整个丰度范围。通过原代皮质神经元体外试验，我们验证了SPARC和PEDF显著参与USSC介导的神经突生长，从而强调了它们在移植后改善运动功能恢复中的作用。从我们的数据中，我们确信USSC是再生医学中的一种有价值工具，因为USSC的分泌组包含一个营养因子综合网络，不仅通过单一过程支持神经再生，还通过多种相关生物学过程维持其再生表型。
Zotero 插件