Placenta-Derived Stem Cells PDF

Dr. Mohamed Elkhawanky  Placenta is an extrafetal organ essential for fetal development.  Facilitates the exchange of nutrients, oxygen, and waste products.  It is a rich reservoir of stem cells, making it a significant contributor to advancements in regenerative me...

Dr. Mohamed Elkhawanky  Placenta is an extrafetal organ essential for fetal development.  Facilitates the exchange of nutrients, oxygen, and waste products.  It is a rich reservoir of stem cells, making it a significant contributor to advancements in regenerative medicine, immune modulation and disease modeling.  The placenta develops from fetal and maternal tissues.  Begins after implantation of the blastocyst into the uterine wall, from the trophoblast layer of the blastocyst.  Trophoblast layer differentiates into cytotrophoblasts and syncytiotrophoblasts.  Syncytiotrophoblasts infiltrate the uterine lining, establishing the early interface between maternal and fetal systems.  Cytotrophoblasts expand and differentiate, forming finger-like villi.  Chorionic Plate: The fetal side of placenta contains the umbilical arteries and vein.  Chorionic Villi: Embedded within the maternal blood pools, finger-like projections contain capillaries that facilitate nutrient and gas exchange.  Basal Plate: The maternal side of placenta, where maternal blood flows in proximity to fetal tissues. Within these layers the placenta microenvironment supports various types of stem cells.  p-SCs are in between embryonic and mesenchymal stem cells, sharing characteristics with both.  Non-carcinogenic  Potentially exceeds mesenchymal stem cells in its ability to differentiate into cells from other germ layers.  Not ethically restricted.  Placenta has a fundamental role in maintaining fetomaternal tolerance and, therefore, it has immunomodulatory properties.  Pluripotency is a characteristic of the ICM and is related to the expression Oct4. Oct4 is essential to prevent ICM from diverting towards the trophectoderm (TE) lineage.  Another transcription factor, Cdx2, is specifically expressed in TE. It inhibits the expression of Oct4 in TE. Moreover, Cdx2 null embryos exhibit high incidence of apoptosis.  Mesenchymal Stem Cells (PD-MSCs): can differentiate into osteoblasts, chondrocytes, adipocytes, and other mesodermal lineages. These cells are highly proliferative, immunomodulatory, and exhibit low immunogenicity, making them ideal for transplantation.  Hematopoietic Stem Cells (HSCs): can develop and differentiate into all types of blood cells, including white blood cells, red blood cells, and platelets.  Trophoblast Stem Cells (TSCs): TSCs contribute to the formation of the placenta itself, playing a role in early trophoblast development. They are crucial for understanding placental biology.  Amniotic Epithelial Cells (AECs): AECs are found on the fetal side of placenta.  Positive for markers 73, 90, and 166, and negative for 11b, 34, and 45.  Also positive for human leukocyte antigen class I (HLA-A, -B, -C) and negative for HLA class II (HLA- DR, -DP, -DQ). Low immunogenicity due to low expression of MHC class II molecules.  Ethical accessibility: The placenta is typically discarded after birth, making p-SCs a non-controversial source compared to ESCs, which are derived from embryos.  Immunomodulatory properties: p-SCs are less likely to trigger immune reactions, allowing for potential allogeneic transplantation without stringent immunosuppression.  High proliferative capacity: p-SCs proliferate rapidly in culture, enabling the generation of large cell quantities for research or therapeutic use.  Low tumorigenicity: Unlike ESCs and induced pluripotent stem cells (iPSCs), p-SCs are less prone to forming teratomas.  Paracrine effects: p-SCs secrete bioactive factors that promote tissue repair, angiogenesis, and anti-inflammatory responses, enhancing their therapeutic benefits.  Proper for clinical use: because of their stability in subcultures, availability, freezing resistance and high viability after thawing.  p-SCs maintain high cell division rates and a stable karyotype even at subculture 30.  In contrast, most other MSCs (adult or induced) lose replicative ability and show reduced cell survival around subcultures 8 to 10.  p-SCs (via intravenous administration) significantly increased vascular endothelial growth factor (VEGF), and brain derived neurotrophic factor (BDNF) levels in the ischemic brain compared to controls after middle cerebral artery occlusion.  Two different approaches that are currently used arbitrarily in various laboratories worldwide: one involving insertion of a monofilament via the common carotid artery (Koizumi et al.) and one via the external carotid artery (Longa et al.).  It was demonstrated that p-SCs transplanted into an Alzheimer’s disease mouse model modulated the properties of microglial cells toward the damaged neural cells and β-amyloid peptide plaque, inducing anti-inflammatory response.  p-SCs showed a great potential for hepatogenic differentiation and proliferation in vitro.  p-SCs could trigger autophagy to enhance regeneration in carbon tetrachloride injured rat liver model. CCl₄ is metabolized by liver enzymes producing reactive free radicals, leading to lipid peroxidation, protein and DNA damage, and eventual cell death in hepatocytes (liver cells).  p-SCs have the potential to differentiate into insulin- secreting β-cells, restoring normoglycemia when transplanted into streptozotocin-induced diabetic mice.  p-SCs were intramyocardial injected in a pig model, treated with hyaluronic acid.  Treated animals showed smaller infarct scar size and a significant improvement of the heart wall thickening. Techniques for injection into porcine tissue. Angling the needle parallel to myocardium will allow for penetration directly into myocardium without injection into the ventricle. Hydrogel injection into sites marked by titanium markers, finger placement to prevent leak of material after injection as the needle is withdrawn, and 9 injection sites marked by titanium markers following injection into the infarct.  P-SCs could be efficiently directed for potential therapeutic use in Duchenne muscular dystrophy, which is a X-linked disorder characterized by the absence of dystrophin at the sarcolemma of muscle fibers. Duchenne muscular dystrophy  On a mouse model of bleomycin-induced lung fibrosis, cellular therapy using p-SCs promoted a decrease in neutrophil infiltration and a significant reduction in the severity of fibrosis, compared to control.  It was demonstrated that intraperitoneal injection of p-SCs in osteogenesis imperfecta neonates reduced fractures and increased bone density.  Regenerative medicine using p-SC for bone disease (large lytic lesions) secondary to multiple myeloma was investigated.  It was found that p-SCs has inhibitory effects on myeloma bone disease and tumor growth were dose- dependent through intra-bone engraftment of p-SCs.  The p-SCs promote apoptosis in osteoclast precursors and inhibited their differentiation, indicating a promising therapeutic approach for myeloma osteolysis.  The utility of p-SCs for bone tissue engineering.  Transplantation of human p-SCs growing on a silk fibroin/hydroxyapatite scaffold into injured radius segmental bone in rabbits enhances bone regeneration.  On an elastic scaffold, p-SCs cultured for 14 days start differentiating toward a cardiomyogenic lineage.