![]() ![]() This includes highly efficient technologies for the transgene-free reprogramming of easily accessible cell sources, such as blood ( 6), efficient and safe site-specific genetic engineering of iPSCs ( 7), and the development of technologies for the expansion and differentiation of iPSCs at clinical scale ( 8). ![]() Intense research has driven forward dramatic progress in virtually all areas of iPSC technology. The availability of human pluripotent stem cells (PSCs), including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) ( 4), with their far-reaching potential for proliferation and differentiation, now offers novel opportunities for basic research, disease modeling and drug discovery ( 5), as well as for the development of cellular therapies. ![]() Instead, introduction of therapeutic or reporter transgenes into adult stem and progenitor cells is usually achieved through viral vectors with their well-known drawbacks, including limited transient transgene expression, insertional mutagenesis, and in vivo immunogenicity ( 3). Another limitation for experimental evaluation and clinical application of different adult stem and progenitor cells is the typical inability to achieve efficient targeted genome engineering, for instance, to introduce therapeutic transgenes or to correct disease-causing mutations, followed by subsequent isolation of defined transgenic single cell clones. Whereas the application of adult stem and progenitors is promising or has already proven successful in case of tissue types that show considerable endogenous potential for regeneration, such as bone or the hematopoietic system ( 2), treatment of diseases that affect less regenerative organs, such as the brain and the heart ( 1), has not shown significant therapeutic effects, or the observed therapeutic benefit was due to paracrine effects. Major limitations of the various adult stem and progenitor cell types that had been applied include the restricted potential for culture expansion and especially differentiation into the desired therapeutic cell lineages. Stem-cell-based concepts are widely considered as promising, but recent experimental and clinical studies applying various adult stem cells, for instance, for cardiac repair ( 1), have yielded for the most part disappointing results, in many cases without evidence of any considerable functional improvement or therapeutic effects. On the other hand, the increasing frequency of chronic and age-related diseases, lifestyle diseases, or diseases caused by environmental pollution have created new challenges for medical research, including a clear need to develop novel regenerative therapies. Modern medical technologies with the countless number of available drugs, new diagnostic procedures, and therapeutic applications including complex surgical interventions greatly contributed to a substantially increased life expectancy not only in industrialized countries. Nevertheless, PSC technologies obviously have come of age and matured to a stage where various clinical applications of PSC-based cellular therapies have been initiated and are conducted. Moreover, current hurdles such as low survival rates and insufficient functional integration of cellular transplants remain to be overcome. It is noteworthy, however, that for many applications critical requirements such as the targeted specification into distinct cellular subpopulations and a proper cell maturation remain to be achieved. Major progress has already been achieved with regard to reprogramming technology, but also regarding targeted genome editing and scalable expansion and differentiation of iPSCs and ESCs, in some cases yielding highly enriched preparations of well-defined cell lineages at clinically required dimensions. Induced pluripotent stem cells (iPSCs) combine the advantages of adult stem cells with the hitherto unique characteristics of embryonic stem cells (ESCs). Stem-cell-based therapies are considered to be promising and innovative but complex approaches.
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