Induced pluripotent stem cells, a giant leap for mankind therapeutic applications

Induced pluripotent stem cells(iPSC)technology has propelled the field of stem cells biology,providing new cells to explore the molecular mechanisms of pluripotency,cancer biology and aging.A major advantage of human iPSC,compared to the pluripotent embryonic stem cells,is that they can be generated from virtually any embryonic or adult somatic cell type without destruction of human blastocysts.In addition,iPSC can be generated from somatic cells harvested from normal individuals or patients,and used as a cellular tool to unravel mechanisms of human development and to model diseases in a manner not possible before.Besides these fundamental aspects of human biology and physiology that are revealed using iPSC or iPSC-derived cells,these cells hold an immense potential for cell-based therapies,and for the discovery of new or personalized pharmacological treatments for many disorders.Here,we review some of the current challenges and concerns about iPSC technology.We introduce the potential held by iPSC for research and development of novel health-related applications.We briefly present the efforts made by the scientific and clinical communities to create the necessary guidelines and regulations to achieve the highest quality standards in the procedures for iPSC generation,characterization and long-term preservation.Finally,we present some of the audacious and pioneer clinical trials in progress with iPSC-derived cells.

CITED2 and the modulation of the hypoxic response in cancer

CITED2(CBP/p300-interacting transactivator with Glu/Asp-rich C-terminal domain,2)is a ubiquitously expressed protein exhibiting a high affinity for the CH1 domain of the transcriptional co-activators CBP/p300,for which it competes with hypoxia-inducible factors(HIFs).CITED2 is particularly efficient in the inhibition of HIF-1α-dependent transcription in different contexts,ranging from organ development and metabolic homeostasis to tissue regeneration and immunity,being also potentially involved in various other physiological processes.In addition,CITED2 plays an important role in inhibiting HIF in some diseases,including kidney and heart diseases and type 2-diabetes.In the particular case of cancer,CITED2 either functions by promoting or suppressing cancer development depending on the context and type of tumors.For instance,CITED2 overexpression promotes breast and prostate cancers,as well as acute myeloid leukemia,while its expression is downregulated to sustain colorectal cancer and hepatocellular carcinoma.In addition,the role of CITED2 in the maintenance of cancer stem cells reveals its potential as a target in non-small cell lung carcinoma and acute myeloid leukemia,for example.But besides the wide body of evidence linking both CITED2 and HIF signaling to carcinogenesis,little data is available regarding CITED2 role as a negative regulator of HIF-1αspecifically in cancer.Therefore,comprehensive studies exploring further the interactions of these two important mediators in cancer-specific models are sorely needed and this can potentially lead to the development of novel targeted therapies.