# The Long and Winding Road to Cardiac Regeneration
## 3 Tissue Engineering  
The field of regenerative medicine has witnessed remarkable strides in recent years, with engineered cardiac constructs emerging as a promising approach for addressing the pressing need for effective treatments for heart diseases. These constructs, meticulously designed to mimic the intricacies of native cardiac tissue, hold the potential to revolutionize therapeutic approaches [165, 166]. Perclinical studies have laid the foundation for the development and optimization of engineered cardiac constructs. In vitro models, such as 3D cell cultures and tissue-engineered platforms, have provided invaluable insights into the behavior of these constructs under controlled conditions. These investigations have enabled researchers to fine-tune factors such as cell source, scaffold materials, and biomechanical cues to enhance construct functionality and integration. Moreover, animal models have served as vital testing grounds for engineered cardiac constructs, offering a bridge between in vitro exper \begin{table}
\begin{tabular}{c c c c c c} \hline \hline
**Stem Cells** & **Cell Type** & **Source** & **Advantages** & **Disadvantages** & **Refs.** \\ \hline \multirow{4}{*}{Skeletal Myoblasts (SMs)} & \multirow{4}{*}{Skeletal muscle biopsies} & High proliferation rate, resilient to myocardial ischemia, improve left ventricular function & Associated with increased risk of ventricular arrhythmias & [93, 94, 95, 96, 97] \\  & & & Abundant availability, ability to self-renew and differentiate into blood and cardiac cell lineages & Immunogenicity, low efficiency of differentiation into cardiac cell lineages & [98, 99, 100, 101, 102, 103, 104] \\  & & & & \\ \multirow{4}{*}{Hematopoietic stem cells (HSCs)} & Bone marrow of adult organisms & Abundant availability, ability to self-renew and differentiate into blood and cardiac cell lineages & Immunogenicity, low efficiency of differentiation into cardiac cell lineages & [98, 99, 100, 101, 102, 103, 104] \\  & & & & \\ \multirow{4}{*}{Endothelial progenitor cells (EPCs)} & Bone marrow, peripheral blood, umbilical cord & Immunomodulatory properties, angiogenic potential, capability to promote the recruitment of other regenerative cells to injured cardiac tissue & Low number and limited lifespan in the peripheral blood, reduced regenerative potential & [105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125] \\  & & & & \\ \multirow{4}{*}{**Adult stem cells**} & Bone marrow, adipose tissue, umbilical cord & Immunomodulatory properties, angiogenic potential, modulation of fibrosis and enhancement of the survival of existing cardiomyocytes & Heterogeneity, propensity to undergo senescence during expansion & [116, 117, 118, 119, 120, 121, 122] \\  & & & & \\ \multirow{4}{*}{Mesenchymal stem cells (MSCs)} & Bone marrow, adipose tissue, umbilical cord & Animal-inflammatory properties, angiogenic potential, modulation of fibrosis and enhancement of the survival of existing cardiomyocytes & Heterogeneity, lack of specific markers & [123, 124, 125, 126, 127, 128, 129, 130] \\  & & & & \\ \multirow{4}{*}{Cardiac progenitor cells (CPCs)} & Embryonic, fetal, and adult heart & Ability to differentiate into cardiomyocytes, endothelial cells and smooth muscle cells, secretion of growth factors and cytokines for tissue repair and remodeling & [131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141] \\  & & & & \\ \multirow{4}{*}{**Pluripot stem cells**} & Embryonic stem cells (ESCs) & Inner cell mass of the early-stage embryos & High regenerative and differentiative potential, self-renewal & Ethical concerns, immunogenicity and tumorigenicity & [134, 135, 136, 137, 138, 139, 141] \\  & & & & \\ \multirow{4}{*}{**Cells**} & Induced & \multirow{4}{*}{Adult somatic cells (iPSCs)} & Versatility, easy manipulation & Immunogenicity and tumorigenicity & [142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164] \\  & & & & \\ \hline \hline \end{tabular}
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