Abstract
Heart disease is the most common cause of death in developed countries, but the medical treatments for heart failure remain limited. In this context, the development of cardiac regeneration therapy for severe heart failure is important. Owing to their unique characteristics, including multiple differentiation and infinitive self-renewal, pluripotent stem cells can be considered as a novel source for regenerative medicine. Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signaling plays critical roles in the induction, maintenance, and differentiation of pluripotent stem cells. In the heart, JAK/STAT3 signaling has diverse cellular functions, including myocardial differentiation, cell cycle re-entry of matured myocyte after injury, and anti-apoptosis in pathological conditions. Therefore, regulating STAT3 activity has great potential as a strategy of cardiac regeneration therapy. In this review, we summarize the current understanding of STAT3, focusing on stem cell biology and pathophysiology, as they contribute to cardiac regeneration therapy. We also introduce a recently reported therapeutic strategy for myocardial regeneration that uses engineered artificial receptors that trigger endogenous STAT3 signal activation.
Highlights
Pluripotent stem cells (PSC) are a cell type characterized by unlimited self-renewal and pluripotency
There are two major states of pluripotency observed in mouse embryonic stem cells (ESCs) and epiblast stem cells (EpiSCs): the former is isolated from the pre-implantation embryo and is termed the naïve PSC; the latter is derived from the post-implantation epiblasts and termed the primed PSC
The link between the LIF receptor (LIFR)/JAK/STAT3 signaling pathway and the core circuitry of pluripotency-associated transcription factors composed of OCT4, SOX2, KLF4, and NANOG has been thoroughly analyzed in a previous paper [13]
Summary
Pluripotent stem cells (PSC) are a cell type characterized by unlimited self-renewal and pluripotency Owing to these cellular properties, PSCs, including embryonic stem cells (ESCs), epiblast stem cells (EpiSCs), and induced pluripotent stem cells (iPSCs), have been extensively studied for advancing regenerative medicine, including cell therapy with or without gene engineering. Determining the gene expression profiles during embryonic development and how they are dynamically changed afterward is promising for the identification of the novel molecules or signal pathways involved in the pluripotency signature, other than Oct, Sox, and Nanog, which are common markers of PSCs. One critical pathway is the Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) pathway, which has been utilized for the acquisition and maintenance of pluripotency in culture. An in-depth understanding of cellular pluripotency is necessary for utilizing PSCs in clinical applications
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