Good manufacturing practices production of human placental derived mesenchymal stem cells for therapeutic applications: focus on multiple sclerosis.

BACKGROUND: Among neurological diseases, multiple sclerosis (MS) affects mostly young adults and can cause long-term disability. While most medications with approval from regulatory agencies are very effective in treating MS disease, they are unable to repair the tissue damage found in the central nervous system (CNS). Consequently, Cell-based therapy particularly using mesenchymal stem/stromal cells (MSCs), holds promise for neuroprotection and tissue repair in MS treatment. Furthermore, placenta-derived MSCs (PLMSCs) have shown the potential to treat MS due to their abundance, noninvasive isolation from discarded tissues, no ethical problems, anti-inflammatory, and reparative properties. Accordingly, good manufacturing practices (GMPs) plays a crucial part in clinical SCs manufacturing. The purpose of our article is to discuss GMP-grade PLMSC protocols for treating MS as well as other clinical applications. METHODS AND RESULTS: Placental tissue obtained of a healthy donor during the caesarean delivery and PLMSCs isolated by GMP standards. Flow cytometry was used to assess the expression of the CD markers CD34, CD105, CD90, and CD73 in the MSCs and the mesodermal differentiation ability was evaluated. Furthermore, Genetic evaluation of PLMSCs was done by G-banded karyotyping and revealed no chromosomal instability. In spite of the anatomical origin of the starting material, PLMSCs using this method of culture were maternal in origin. CONCLUSIONS: We hope that our protocol for clinical manufacturing of PLMSCs according to GMP standards will assist researchers in isolating MSCs from placental tissue for clinical and pre-clinical applications.

Assessment of the relationship between the dopaminergic pathway and severe acute respiratory syndrome coronavirus 2 infection, with related neuropathological features, and potential therapeutic approaches in COVID-19 infection.

Dopamine is a known catecholamine neurotransmitter involved in several physiological processes, including motor control, motivation, reward, cognition, and immune function. Dopamine receptors are widely distributed throughout the nervous system and in immune cells. Several viruses, including human immunodeficiency virus and Japanese encephalitis virus, can use dopaminergic receptors to replicate in the nervous system and are involved in viral neuropathogenesis. In addition, studies suggest that dopaminergic receptors may play a role in the progression and pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. When SARS-CoV-2 binds to angiotensin-converting enzyme 2 receptors on the surface of neuronal cells, the spike protein of the virus can bind to dopaminergic receptors on neighbouring cells to accelerate its life cycle and exacerbate neurological symptoms. In addition, recent research has shown that dopamine is an important regulator of the immune-neuroendocrine system. Most immune cells express dopamine receptors and other dopamine-related proteins, indicating the importance of dopaminergic immune regulation. The increase in dopamine concentration during SARS-CoV2 infection may reduce immunity (innate and adaptive) that promotes viral spread, which could lead to neuronal damage. In addition, dopaminergic signalling in the nervous system may be affected by SARS-CoV-2 infection. COVID -19 can cause various neurological symptoms as it interacts with the immune system. One possible treatment strategy for COVID -19 patients could be the use of dopamine antagonists. To fully understand how to protect the neurological system and immune cells from the virus, we need to study the pathophysiology of the dopamine system in SARS-CoV-2 infection.

The effects of prolactin on the immune system, its relationship with the severity of COVID-19, and its potential immunomodulatory therapeutic effect.

Prolactin (PRL) is an endocrine hormone secreted by the anterior pituitary gland that has a variety of physiological effects, including milk production, immune system regulation, and anti-inflammatory effects. Elevated levels of PRL have been found in several viral infections, including 2019 coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), a viral pathogen that has recently spread worldwide. PRL production is increased in SARS-CoV2 infection. While PRL can trigger the production of proinflammatory cytokines, it also has several anti-inflammatory effects that can reduce hyperinflammation. The exact mechanism of PRL's contribution to the severity of COVID-19 is unknown. The purpose of this review is to discuss the interaction between PRL and SARS-CoV2 infection and its possible association with the severity of COVID-19.

The role of DNA methylation in progression of neurological disorders and neurodegenerative diseases as well as the prospect of using DNA methylation inhibitors as therapeutic agents for such disorders.

Genome-wide studies related to neurological disorders and neurodegenerative diseases have pointed to the role of epigenetic changes such as DNA methylation, histone modification, and noncoding RNAs. DNA methylation machinery controls the dynamic regulation of methylation patterns in discrete brain regions. Objective: This review aims to describe the role of DNA methylation in inhibiting and progressing neurological and neurodegenerative disorders and therapeutic approaches. Methods: A Systematic search of PubMed, Web of Science, and Cochrane Library was conducted for all qualified studies from 2000 to 2022. Results: For the current need of time, we have focused on the DNA methylation role in neurological and neurodegenerative diseases and the expression of genes involved in neurodegeneration such as Alzheimer's, Depression, and Rett Syndrome. Finally, it appears that the various epigenetic changes do not occur separately and that DNA methylation and histone modification changes occur side by side and affect each other. We focused on the role of modification of DNA methylation in several genes associated with depression (NR3C1, NR3C2, CRHR1, SLC6A4, BDNF, and FKBP5), Rett syndrome (MECP2), Alzheimer's, depression (APP, BACE1, BIN1 or ANK1) and Parkinson's disease (SNCA), as well as the co-occurring modifications to histones and expression of non-coding RNAs. Understanding these epigenetic changes and their interactions will lead to better treatment strategies. Conclusion: This review captures the state of understanding of the epigenetics of neurological and neurodegenerative diseases. With new epigenetic mechanisms and targets undoubtedly on the horizon, pharmacological modulation and regulation of epigenetic processes in the brain holds great promise for therapy.

Molecular signaling pathways, pathophysiological features in various organs, and treatment strategies in SARS-CoV2 infection.

Cytokine storms and extra-activated cytokine signaling pathways can lead to severe tissue damage and patient death. Activation of inflammatory signaling pathways during Cytokine storms are an important factor in the development of acute respiratory syndrome (SARS-CoV-2), which is the major health problem today, causing systemic and local inflammation. Cytokine storms attract many inflammatory cells that attack the lungs and other organs and cause tissue damage. Angiotensin-converting enzyme 2 (ACE2) are expressed in a different type of tissues. inhibition of ACE2 activity impairs renin-angiotensin (RAS) function, which is related to the severity of symptoms and mortality rate in COVID-19 patients. Different signaling cascades are activated, affecting various organs during SARS-CoV-2 infection. Nowadays, there is no specific treatment for COVID-19, but scientists have recognized and proposed several treatment alternatives, including applying cytokine inhibitors, immunomodulators, and plasma therapy. Herein, we have provided the detailed mechanism of SARS-CoV-2 induced cytokine signaling and its connection with pathophysiological features in different organs. Possible treatment options to cope with the severe clinical manifestations of COVID-19 are also discussed.

A focus on allogeneic mesenchymal stromal cells as a versatile therapeutic tool for treating multiple sclerosis.

Multiple sclerosis (MS) is a central nervous system (CNS) chronic illness with autoimmune, inflammatory, and neurodegenerative effects characterized by neurological disorder and axonal loss signs due to myelin sheath autoimmune T cell attacks. Existing drugs, including disease-modifying drugs (DMD), help decrease the intensity and frequency of MS attacks, inflammatory conditions, and CNS protection from axonal damage. As they cannot improve axonal repair and show side effects, new therapeutic options are required. In this regard, due to their neuroprotection properties, immunomodulatory effects, and the ability to differentiate into neurons, the transplantation of mesenchymal stromal cells (MSCs) can be used for MS therapy. The use of adipose-derived MSCs (AdMSCs) or autologous bone marrow MSCs (BMSCs) has demonstrated unexpected effects including the invasive and painful isolation method, inadequate amounts of bone marrow (BM) stem cells, the anti-inflammatory impact reduction of AdMSCs that are isolated from fat patients, and the cell number and differentiation potential decrease with an increase in the age of BMSCs donor. Researchers have been trying to search for alternate tissue sources for MSCs, especially fetal annexes, which could offer a novel therapeutic choice for MS therapy due to the limitation of low cell yield and invasive collection methods of autologous MSCs. The transplantation of MSCs for MS treatment is discussed in this review. Finally, it is suggested that allogeneic sources of MSCs are an appealing alternative to autologous MSCs and could hence be a potential novel solution to MS therapy.

Standard Operating Procedure for the Good Manufacturing Practice-Compliant Production of Human Endometrial Stem Cells for Multiple Sclerosis.

Multiple sclerosis (MS) is the most common cause of neurological diseases. Although, there are some effective medications with regulatory approval for treating MS, they are only partially effective and cannot promote repairing of tissue damage directly which occurs in the central nervous system. Therefore, there is an essential need to develop novel therapeutic approaches for neuroprotection or repairing damaged tissue in MS. Accordingly, cell-based therapies as a novel therapeutic strategy have opened a new horizon in treatment of MS. Each setting in cell therapy has potential benefits. Human endometrial stem cells as an invaluable source for cell therapy have introduced treatment for MS. In this respect, good manufacturing practice (GMP) has a pivotal role in clinical production of stem cells. This chapter tries to describe the protocol of GMP-grade endometrial stem cells for treatment of MS.