iPSCs are somatic cells that have been reprogrammed to become ESC-like.Therefore,iPSCs are pluripotent and can give rise to any germ line.To generate iPSCs,cells are forced to express genes fortranscription factors that are required for pluripotency and self-renewal。
As with VSELs,the development of iPSCs for therapeutics has the advantage that they can potentially be used for autologous transplantation and so immunocompatibility is not a problem,because the cells to be reprogrammed can be obtained from the patient。
iPSCs were first generated by introducing the transcription factors Oct3/4,Sox2,Klf4,and c-Myc into cells maintained in the same culture conditions used for ESC(Takahashi and Yamanaka,2006)。ast iPSC cell lines have been generated using viral transduction by retroviruses or lentiviruses.(For more information,iPSC section in隔离和维护)。
Insome iPSC lines,there is incomplete silencing of integrated viral genes upon differentiation,which increases the risk of tumor development.When iPSCs are injected into immune-deficient mice,they readily form teratomas.It has been suggested that iPSCs are more tumorigenic than ESCs(Gutier2010)。Additionally,as with ESCs,adaptation to culture and passaging increases the likelihood of development of mosaic populations and chromosomal abnormalities。
Although iPSCs potentially have many advantages for in vivo stem cell treatments,there are still a number of technical hurdles to overcome.For instance,one consideration for iPSCs is epigenetic memory.During development,patterns ofgenomic DNAchange.There is evidence that reprogramming of somatic cells may not reverse all changes in methylation that occurred during differentiation and maturation.This can mean that some iPSCs are not truly pluripotent,since they retain lineage or tissue specificity.However,this could potentially be exploited renerative,apy, by using iPSCs generated from cells in the same lineage as the target cell type。
One area where iPSCs are proving very valuable is for models of development,tissue differentiation,and disease.Most research on diseases relies on animal models,which may,or may not, accurately mimic a disease.The ability to be able to generate cultures of human or animal iPSC cultures provides new ways to follow cell differentiation and the direction of changes in cellular and molecular mechanism in normal tissues and in disease progression.The availability of populations of cells with finefifined of fetyes andrs cheaper,better,and more targeted drug development and preclinical testing(see)Stem Cells as Modelson the,on theStem Cells in Therapeutics and Researchpage)。
Chimeric mice produced by injection of MEF iPS cells into heterologous blastocysts。Image courtesy of Dr.Miguel Esteban,Stem Cell and Cancer Biology Group,Key Laboratory of Regenerative Biology,South China Institute for Stem Cell Biology and Regenerative Medicine,Guangzhou Institues of Biomedicine and Health,Chines Academy of Sciences,Guangzhou510663,China,mouse embryonic fibroblasts.)
Somatic Cell Nuclear Transfer(SCNT)is the transfer of a somatic nucleus to an enucleated egg(i.e.an isolated nucleus from a differentiated cell inserted into an egg without a nucleus)。This technique was used to make Dolly the sheep(Wilmut et al.1997)。The somatic nucleus is reprogrammed by the egg to become pluripotent.These cells are effectively iPSCs and can be used to generate cell lines.Though this technique has been used in animal stem cell research formany years,thought only recently has human SCNT been reported(Tachibaet al.2013)。