Cardiac Restoration Stemming From the Placenta Tree: Insights From Fetal and Perinatal Cell Biology

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.

Message in a Bottle: Upgrading Cardiac Repair into Rejuvenation

“…Indeed, foetal and perinatal MSCs are immature progenitors with high self-renewal potential, have significant immunomodulatory properties and distinct pro-angiogenic, cytoprotective and anti-inflammatory paracrine profile. Foetal and perinatal sources include amniotic fluid and term umbilical cord and placenta, respectively, from which MSC can be easily isolated without any ethical concern [198]. EVs from umbilical cord-derived MSCs (UC-MSC-EVs) have been recently broadly scrutinised in terms of their beneficial effects in different preclinical animal models of myocardial injury.…”

Comprehensive Profiling of Secretome Formulations from Fetal- and Perinatal Human Amniotic Fluid Stem Cells

“…From a translational perspective, on top of cell modulatory potential, isolation feasibility and elevated self-renewal are key aspects for the ideal source of therapeutic EVs and soluble factors. In such a scenario, fetal- and perinatal MSC may offer an interesting option given their proliferative potential, and developmentally immature profile with intermediate features between embryonic and adult somatic progenitors [ 10 , 11 ]. Fetal MSC can be isolated from extra-embryonic annexes during gestation as left-over sampling obtained during prenatal screening (i.e., chorionic villi [ 12 , 13 , 14 ] and amniotic fluid [ 15 , 16 ]) or obtained as perinatal progenitors at birth, from clinical waste material (i.e., amniotic and placenta membranes [ 17 , 18 , 19 , 20 , 21 ], umbilical cord components [ 22 , 23 , 24 ] and term amniotic fluid [ 25 , 26 ]).…”

Clinical-based Cell Therapies for Heart Disease—Current and Future State

“…Many of these cells display MSC-like characteristics, such as adherence to plastic and immunomodulation. Furthermore, in vitro, they inhibit cardiomyocyte apoptosis and are pro-angiogenic (reviewed by Bollini et al 117 ).…”