*2.3.1. Parkinson's disease*

Parkinson's disease (PD) is a progressive neurodegenerative disease associated with a specific loss of dopaminergic neurons in the substantia nigra and depletion of dopamine levels in the striatum. The main therapeutic objective in PD is the recovery of dopaminergic neurotransmission in the striatum. Cellular replacement has been emerged as a suitable therapeutic strategy. First-trimester human PMSC differentiated to neural progenitors and transplanted into the striatum of a rat model of PD, underwent dopaminergic differentiation and showed an attenuation of the symptoms [69]. PD motor pathology is also accompanied by other disabilities, such as, mood disorders, constipation, and hyposmia. It is expected that besides the regenerative effects of PMSC, the secretion of trophic factors, their anti-inflammatory and antiapoptotic effects, could also alleviate these nonmotor symptoms.

#### *2.3.2. Alzheimer's disease*

Alzheimer's disease (AD) pathogenesis is characterized by a deposition of β-amyloid peptide and hyperphosphorylation of tau causing loss of the synaptic and neuronal activities and neuroinflammation. It has been demonstrated that PMSC, transplanted into an Alzheimer's disease mouse model, modulated the inflammatory response. Moreover, mice injected with PMSC presented higher levels of β-amyloid degrading enzymes, reduced levels of pro-inflammatory cytokines, and increased levels of anti-inflammatory cytokines (TGF-β and IL-10). The effect of PMSC injection resulted in an improvement of memory function [70].

abnormalities in which physiological bone regeneration is not sufficient. There are also other conditions, such as osteoporosis, in which regeneration is compromised. PMSC have the potential to differentiate into osteogenic lineage, and seem to be an appropriate therapeutic option for bone regeneration. The use of 3D scaffolds that support cell differentiation and improve engraftment has become habitual in PMSC-mediated bone regeneration therapy. Several published studies confirm that PMSC have potent in vivo bone-forming capacity and may be worthwhile candidates for in vivo bone tissue repair. So, when PMSC were subcutaneously injected into severe combined immunodeficiency (SCID) mice with hydroxyapatite/tricalcium phosphate particles as a vehicle, new bone formation was found throughout all implants [75]. Another study showed that PMSC administered in combination with nanobiphasic calcium phosphate ceramics in a rat model of femur bone defects produced complete healing of the

Human Placenta-Derived Mesenchymal Stromal Cells: A Review from Basic Research to Clinical Applications

http://dx.doi.org/10.5772/intechopen.76718

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Osteoarthritis (OA) is a degenerative process of the cartilage in joints. There is still no treatment available to improve or reverse the degenerative process and current pharmacological treatments are only palliative. Given the potential of PMSC to differentiate into musculoskeletal lineages including bone and cartilage, MSC have been proposed as an optimal regenerative cellular therapy for degenerative musculoskeletal conditions as OA. There are numerous data that support this hypothesis in preclinical models. PMSC embedded in a collagen I gel and transplanted in a rat model of femoral cartilage defect appeared to cover the tissue defects with soft tissue positive for toluidine blue suggesting in vivo differentiation of transplanted cells [77]. Also PMSC grown on silk fibroin and transplanted into the knee in rabbits with knee osteochondral defects resulted in newly created hyaline cartilage without inflammatory response [78]. Similarly, PMSC seeded onto poly lactic-co-glycolic acid (PLGA) and preconditioned in chondrogenic medium were well tolerated and found in the reparative tissue of OA

Cirrhosis is the common end-stage of most of the injuries affecting the liver such as virus infections, chronic alcoholism, metabolic diseases, or acute liver failure. A scar is formed by extracellular matrix, making the normal function of the liver difficult. Cirrhosis is an irreversible state that can become life-threatening and, frequently, liver transplantation is the only alternative for healing. Donor shortage and continuous need for immunosuppression are the main limitations to liver transplant and cell transplantation appears as a suitable alternative. In addition to fetal and adult hepatocytes, stem cells are considered for cell transplantation. PMSC can be helpful since their potential capacity to differentiate to hepatic-like cells and

Transplanted into animal models of disease, PMSC induced a significant reduction of fibrosis and of serum levels of transaminases. Liver regeneration has been proposed to be promoted by the induction of autophagy process [81], stimulation of liver cell proliferation [82], decreased apoptosis, and suppression of stellate cells activation [83]. Although no evidence of differentiation of the transplanted cells into hepatocytes was reported in a CCl4-induced fibrosis rat model [82], in other models, PMSC engraftment and expression of human albumin

defect in 3 months without evidence of fibrosis [76].

rabbit knees 8 weeks after transplantation [79].

and α-fetoprotein have been reported [83–85].

**2.5. Use of placental mesenchymal stem/stromal cells in liver diseases**

form functional three-dimensional structures have been reported [80].

#### *2.3.3. Amyotrophic lateral sclerosis*

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by loss of nerve cells in the brain and spinal cord, leading to muscle weakness, paralysis, respiratory problems, and eventually, death. Multiple intravenous injections of PMSC in a mouse model of ALS, resulted in a protection of motor neurons from inflammatory effectors delaying functional deterioration and increasing lifespan [71].
