Toward the latest advancements in cardiac regeneration using induced pluripotent stem cells (iPSCs) technology: approaches and challenges

Abstract

A novel approach to treating heart failures was developed with the introduction of iPSC technology. Knowledge in regenerative medicine, developmental biology, and the identification of illnesses at the cellular level has exploded since the discovery of iPSCs. One of the most frequent causes of mortality associated with cardiovascular disease is the loss of cardiomyocytes (CMs), followed by heart failure. A possible treatment for heart failure involves restoring cardiac function and replacing damaged tissue with healthy, regenerated CMs. Significant strides in stem cell biology during the last ten years have transformed the in vitro study of human illness and enhanced our knowledge of the molecular pathways underlying human disease, regenerative medicine, and drug development. We seek to examine iPSC advancements in disease modeling, drug discovery, iPSC-Based cell treatments, and purification methods in this article.

Keywords: Cardiac regeneration; Regenerative medicine; Signaling pathways; Stem cell-based therapy; iPSC.

Fig. 1

The graphical representation of Wnt/β-Catenin-dependent signaling. (A) When Wnt ligand is absent (off state), β catenin is phosphorylated by kinases (GSK3 and CK1) of the Destruction complex. Then, phosphorylated β-catenin ubiquitinate to be targeted for degradation in the proteasome. (B) Binding of Wnt ligand to Frizzled receptor and LRP5/6 (on state), allows the Destruction complex to decompose which induce the stabilization of β-catenin. β-catenin accumulates in cytoplasm and then is transferred to the nucleus and starts gene transcription. This figure adapted from Fig. 1 of reference number 25 [25]

Fig. 2

The roles of Wnt/β-catenin signaling in development of cardiomyocytes. Activation of this pathway is essential for mesodermal specification and suppression of this pathway is required during cardiomyocytes differentiation. This figure adapted from Fig. 2 of reference number 30 [30]

Fig. 3

This figure depicts two clusters of TGFβ family signaling, BMP signaling and TGFβ signaling. BMPs (on the right site) bind to BMP type receptor or activin IIA or IIB which send signals via ALK1 or ALK 2, 3 ,6. As a result, SMAD 1, 5, 8 are phosphorylated and by joining SMAD4, this new made complex translocates to the nucleus. On left site, binding of TGFβ 1, 2, 3 to TGFβ receptor II and binding of Nodal, activing and inhibin to activing receptor IIA, respectively activate signaling through ALK5 and ALK4. This signaling leads to phosphorylation of SMAD 2, 3 and then SMAD4 binds to phosphorylated SMAD 2, 3. This complex enters the nucleus and cause gene transcription. This figure adapted from Fig. 1 of reference number 33 [33]

Fig. 4

Various applications of iPSC-derived cardiomyocytes