# The Long and Winding Road to Cardiac Regeneration
## 2 Stem Cell Therapy  
Stem cell therapy has garnered significant attention in recent years for its potential to revolutionize the treatment of cardiac diseases. Stem cells possess a remarkable capability to divide and transform into specialized cells, making them ideal for repairing damaged tissues. Specifically, in case of heart failure and other cardiac diseases, stem cells can regenerate cardiac tissues, offering a promising avenue for treatment [58; 59; 60; 61]. One of the primary advantages of utilizing stem cell therapy for cardiac regeneration lies in its potential to restore lost cardiac function [62; 60; 63; 64]. Recent studies have demonstrated that stem cells can enhance heart function in patients suffering from heart failure by regenerating tissue and reinstating blood flow. For instance, studies published in _The Lancet_[65; 66] and in _Physiological Review_[67] showed that cardiac stem cells improved heart function and reduced scar tissue in patients with heart failure. Furthermore, stem cell therapy has the potential to reduce or even reverse the progression of cardiac diseases. A study published in _Circulation Research_[68] reported that injecting bone marrow-derived stem cells into the hearts of patients with severe heart failure resulted in a significant reduction in major adverse cardiovascular events. Another notable benefit of stem cell therapy for cardiac regeneration is the relative safety of the procedure. Stem cells can be derived from various sources, including the patients' own body, and carry a low risk of triggering immunological reactions [69; 70]. Additionally, stem cell therapy is minimally invasive and could be performed as an outpatient procedure, minimizing the burden on patients [71]. While the potential of stem cell therapy for cardiac regeneration is immense, there are still certain limitations to be addressed. Several studies have revealed drawbacks in current stem cell-based therapies. These limitations include significant cell death and apoptosis,insufficient cell engraftment, limited cardiac regeneration post cell transplantation, and the need for careful monitoring of potential autoimmune adverse reactions [72]. To overcome these limitations, various strategies have been developed. These strategies aim to improve cell survival and engraftment, as well as induce transformation of somatic cells directly into functional cardiomyocytes to stimulate endogenous cardiac regeneration [73]. One such study, published in _Nature_[74], demonstrated successful reprogramming of fibroblasts into cardiomyocyte-like cells using a combination of transcription factors. Cell types used for cardiac regeneration can be broadly categorized into two groups: adult stem cells and pluripotent stem cells [75]. Adult stem cells, such as skeletal myoblasts (SMs), hematopoietic stem cells (HSCs), endothelial progenitor cells (EPCs), mesenchymal stem cells (MSCs), and cardiac progenitor cells (CPCs), can be isolated from different tissues, including skeletal muscle, adipose tissue, peripheral blood, bone marrow, and heart tissue [76; 77]. In addition, pluripotent stem cells, such as embryonic stem cells and induced pluripotent stem cells (reprogrammed somatic cells), possess a clear potential to differentiate into functional cardiomyocytes, setting them apart from adult stem cells [78; 79; 65]. Notably, an important difference between these two categories of cells is that while adult stem cells have a variable cardiogenic transdifferentiation capacity, pluripotent stem cells have an unequivocal potential to differentiate into functional cardiomyocytes [80]. Extensive research has been conducted utilizing these cell types in cardiac regeneration studies, demonstrating their tremendous potential for treating cardiovascular diseases. Adult stem cells and pluripotent stem cells are typically administered via intravascular injections, injections into the pericardium, or infusion of cardiac patches [81].