Abstract
Efficient cardiac repair and ultimate regeneration still represents one of the main challenges of modern medicine. Indeed, cardiovascular disease can derive from independent conditions upsetting heart structure and performance: myocardial ischemia and infarction (MI), pharmacological cardiotoxicity, and congenital heart defects, just to name a few. All these disorders have profound consequences on cardiac tissue, inducing the onset of heart failure over time. Since the cure is currently represented by heart transplantation, which is extremely difficult due to the shortage of donors, much effort is being dedicated to developing innovative therapeutic strategies based on stem cell exploitation. Among the broad scenario of stem/progenitor cell subpopulations, fetal and perinatal sources, namely amniotic fluid and term placenta, have gained interest due to their peculiar regenerative capacity, high self-renewal capability, and ease of collection from clinical waste material. In this review, we will provide the state-of-the-art on fetal perinatal stem cells for cardiac repair and regeneration. We will discuss different pathological conditions and the main therapeutic strategies proposed, including cell transplantation, putative paracrine therapy, reprogramming, and tissue engineering approaches.
Highlights
Reviewed by: Debora Lo Furno, Università di Catania, Italy Sribalasubashini Muralimanoharan, University of Texas Southwestern Medical Center, United States
Cardiovascular disease and heart failure are the main killers in the Western countries representing a significant economic burden for the national health systems, as more than 1 million hospitalizations are annually reported in the EU alone
A major breakthrough for cardiac regenerative medicine has been provided by mounting evidence suggesting that the heart retains an endogenous regeneration programme, very limited, based on cardiac progenitor cell (CPC) activation and cardiomyocyte proliferation
Summary
Upon attachment and invasion into the uterine wall, the embryonic trophoblast concomitant with the embryoblast start differentiating, and together with maternal endometrial transition forming the placental tissues. These tissues establish implantation, support the fetus and maintain pregnancy by orchestrating the maternal adaption. The placenta is further unique in its immunoregulatory functions allowing maternal tolerance and support of the growing embryo/fetus throughout pregnancy (Mori et al, 2016; Vinketova et al, 2016) This highly active organ has been recognized as rich source of human progenitor cells, extracellular matrix and bioactive compounds. With the beginning of the twenty first century, researchers started to realize that cells of placental tissues show distinct stem cell qualities, such as expression of markers of pluripotency (Miki et al, 2007) and the potential to differentiate into lineages of all three germ layers (Kakishita et al, 2003; Takashima et al, 2004; Miki et al, 2005; Portmann-Lanz et al, 2006), as well as paracrine properties such as anti-inflammatory, antibacterial and anti-fibrotic activities, which recommend these cells for regenerative medicine and wound healing applications (Cargnoni et al, 2009, 2014; Lopez-Espinosa et al, 2009; Hong et al, 2010; De et al, 2011; Choi et al, 2013; Ricci et al, 2013; SantAnna et al, 2016)
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