Department of Physiology, Biology School, Universidad Complutense of Madrid, Spain.
Thromb Res. 2011 Jul;128(1):8-13. doi: 10.1016/j.thromres.2011.01.010. Epub 2011 Mar 10.
Human induced pluripotent stem cells (iPSCs) have revolutionized the stem cell field. These iPSCs from somatic cells have been reprogrammed with the introduction of transcription factors and are capable to differentiate into cells from all three germ layers. These strategies require retrovirus transduction or transfection of plasmid vectors strategy without viral transduction. Another promising strategy is based on direct delivery of the reprogramming proteins, addition of signal transduction inhibitors and chemical promoter cell survival. The main advantages of iPSCs cells are that they have not included in the debate over the ethics of embryonic stem cell. Current therapy of haemophilia is based on factor VIII (FVIII) or factor IX (FIX) replacement therapy including prophylactic or demand protocols of fixed-dose, and as future alternative, gene and cell therapy. Gene therapy can be made by using viral vectors, mainly lentiviral (LVV) and adeno-associated viruses (AAV) in adult stem cells and autologous fibroblasts, platelets or haematopoietic stem cells, and transfer using non-viral vectors (NVV). Cell therapy for haemophilia is based, mainly, in transplantation of healthy cells to replace the deficient function, for example, the transplantation of liver sinusoidal endothelial cells or endothelial progenitor cells derived from iPSCs. Recently, as first time in haemophilia, endothelial progenitor cells derived from iPSCs cells express FVIII protein effectively, engraft within the hepatic parenchyma, and functionally integrate to provide the therapeutic benefit for a phenotypic correction in haemophilia. Advanced therapies, gene and cell therapy and tissue engineering or iPSCs technology, can provide a potential clinical application in the treatment of haemophilia and other monogenic disorders. Because to date there are not relevant results for phenotypic correction in haemophilia, iPSCs technology could represent a potential alternative based on cellular therapy.
人类诱导多能干细胞 (iPSC) 彻底改变了干细胞领域。这些源自体细胞的 iPSC 通过引入转录因子进行了重编程，能够分化为来自三个胚层的细胞。这些策略需要逆转录病毒转导或质粒载体的转染策略，而无需病毒转导。另一种有前途的策略基于直接递送电穿孔蛋白，添加信号转导抑制剂和化学促进剂以维持细胞存活。iPSC 的主要优点是它们未包含在胚胎干细胞伦理争论中。目前血友病的治疗基于因子 VIII (FVIII) 或因子 IX (FIX) 替代疗法，包括预防性或按需固定剂量方案，以及作为未来的替代方案，基因和细胞疗法。基因治疗可以通过使用病毒载体（主要是慢病毒 (LVV) 和腺相关病毒 (AAV)）在成体干细胞和自体成纤维细胞、血小板或造血干细胞中进行，并使用非病毒载体 (NVV) 进行转导。血友病的细胞治疗主要基于移植健康细胞以替代功能缺陷，例如，移植肝脏窦内皮细胞或源自 iPSC 的内皮祖细胞。最近，在血友病中首次发现，源自 iPSC 的内皮祖细胞有效表达 FVIII 蛋白，在肝实质内植入，并进行功能整合，为血友病的表型校正提供治疗益处。先进疗法，基因和细胞疗法以及组织工程或 iPSC 技术，可以为血友病和其他单基因疾病的治疗提供潜在的临床应用。由于迄今为止在血友病的表型校正方面没有相关结果，因此 iPSC 技术可能基于细胞疗法代表一种潜在的替代方案。
