Page 56 - BH-2-4

Brain & Heart Stem cells in cardiovascular disease

presents an overview of clinical trials evaluating stem cell Decellularized scaffolds, mimicking the healthy cardiac
therapies for ischemic heart disease. 9-12 tissue, help preserve the native structure ECM and show
Finally, but importantly, there is a recently discovered promise in reducing LV remodeling and improving heart
population of stem cells that have garnered increasing function when engineered into biocompatible materials
16
attention due to their unique properties. Very small such as injectable hydrogels. When combined with
embryonic-like stem cells (VSELs) are small (3–5 μm cardiac patches – laboratory-grown pieces of heart tissue
designed to replace damaged cardiac areas, these scaffolds
smaller than red blood cells) and exhibit pluripotency support heart tissue regeneration and prevent further
similar to that of ESCs. These cells are believed to be damage. 16
13
remnants of ESCs that persist into adulthood, typically
17
remaining in a quiescent state, which may protect them from Prat-Vidal et al. reported the first human application of
environmental damage and teratoma formation. Various an allogeneic decellularized pericardial matrix bioimplant
preclinical models have demonstrated their regenerative with Wharton’s jelly-derived MSCs in patients with
potential, including the regeneration of myocardial myocardial infarction, reducing the scar size by 9% without
post-infarction tissue. Ratajczak, the pioneer in VSEL’ causing adverse effects such as myocarditis. Moreover,
18
research, and his group, have successfully differentiated Sun et al. improved heart function, cell survival, and
13
VSELs in vitro from murine BM into CMs, indicating engraftment by co-transplanting human iPSC (hiPSC)-
their potential for cardiac regeneration. Gounari et al. CMs with preformed microvessels from adipose tissue.
14
successfully differentiated human UCB(hUCB)-VSELs Gene editing is another innovative tool for cardiac care.
into hematopoietic cells in vitro, thereby demonstrating The clustered regularly interspaced short palindromic
their potential for cardiac differentiation through similar repeat system, originally discovered as a bacterial immune
signaling pathways. mechanism, has become a crucial method for disease
19
3. Engineering simulates the 3D cardiac modeling and therapy. It has been used to correct in vitro
mutations in conditions such as Duchenne muscular
environment dystrophy and has improved MSC reparative function for
19
Cardiac tissue engineering addresses previous challenges heart repair both in vitro and in vivo by targeting genes
20
using scaffolds – synthetic, natural, or decellularized – such as TLR4. Furthermore, editing PCSK9 in mice was
21
to support cell growth. These scaffolds can be improved found to significantly reduce cholesterol levels, whereas
with cytokines, growth factors, or peptides to mimic the patient-specific iPSC-derived organoids have been used to
6
physiological conditions of cardiac tissue. This method replicate the heart muscle thickening observed in HCM.
promotes cell attachment and differentiation while These approaches provide novel strategies to prevent heart
protecting cells from the hostile environment of the failure by improving the function of stem cells used for
infarcted myocardium. heart repair.
When comparing natural and synthetic materials, 4. Challenges in stem cell applications for
each has distinct advantages and disadvantages. Natural cardiac care
materials (e.g., fibrin and collagen) are valued for
their biological origin, biocompatibility, and adhesive Stem cells can be transplanted into injured myocardium
sequences that promote cell adhesion and differentiation; either directly or after in vitro differentiation. Furthermore,
however, they often suffer from inadequate mechanical methods such as chemical and drug-based treatments can
properties, rapid degradation, and a risk of contamination, improve cell survival and retention in the myocardium.
which increase production costs. In contrast, synthetic Tissue engineering may further optimize conditions
15
materials (e.g., poly(lactic-co-glycolic) acid) are cost- by better mimicking the natural cardiac environment.
effective and provide consistent mechanical properties; Finally, stem cell-derived exosomes exhibit potential for
however, they have limited scale-up potential, lack cardiac repair. Figure 2 summarizes the pathways for
2,7,22-24
biocompatibility, and pose the risk of biodegradation- improving stem cell efficacy in cardiac regeneration.
related side effects. Therefore, ideally, the scaffold Nonetheless, challenges exist at every step of the process.
15
architecture (surface topography and pore size) should Regarding the appropriate stem cell type, ESC-CM
balance these factors, supporting cell attachment, transplants face significant hurdles, including ventricular
nutrient exchange, cell–extracellular matrix (ECM) arrhythmias, ethical concerns, teratoma formation, and
interactions, and differentiation, along with providing immune rejection. 25,26 Before iPSCs can replace traditional
biocompatibility, mechanical integrity, and controlled PSCs sources, it is essential to investigate the impact of
biodegradability. 15 residual epigenetic and transcriptional anomalies on their

Volume 2 Issue 4 (2024) 6 doi: 10.36922/bh.4521