The properties of hematopoietic stem and progenitor cells (HSPCs), including self-renewal and pluripotency, have been extensively studied. These features have been explored in the management of several haematological disorders and malignancies. Although their role as precursors of innate immune cells is well understood, little is known about their direct participation in host immune response. In this review, we explicate the direct role of HSPCs in the host immune response and highlight therapeutic options for the infectious disease burden that is currently ravaging the world, including COVID-19.
Stem cell therapy is widely used for the treatment of disorders of the blood and immune system but there is comparatively less research devoted to its efficacy in infectious diseases. Although several antibiotics and antivirals have been discovered for the treatment of infectious diseases, a new challenge is posed to the researchers due to the emergence of multiple drug resistance in infectious agents. Infectious agents like SARS COV-2, Mtb (Mycobacterium tuberculosis), HIV and Hepatitis can cause severe tissue and organ damage which can be irreparable. Stem cells, owing to their ability to pervade into the injured region, regenerate and modulate the immune function, can be used as a method to reverse this damage. With the dramatic increase in the number of cases caused by the COVID-19 pandemic, it has become crucial to manage the most severe symptoms such as Acute Respiratory Distress Syndrome (ARDS) and sepsis which have shown promising improvement with the administration of Mesenchymal Stem cells (MSCs) in ongoing clinical trials. This review discusses the scope of stem cell therapy to control some of the most fatal symptoms observed in various infectious diseases. © 2021 Nova Science Publishers, Inc.
Background and objectives: Drug delivery by nebulization has become a crucial strategy for treating different respiratory and lung diseases. Emerging evidence implicates stem cell therapy as a promising tool in treating such conditions, not only by alleviatingthe related symptoms but by improving the prognosis. However, delivery of human peripheral blood-derived stem cells (hPBSCs) to the respiratory airways remains an innovative approach yet to be realized. This study is an analytic, translational, and in vitro research to assess the viability and morphological changes of identified cell populations in hPBSCs cocktail derived from COVID-19 patients. Methods and results: Peripheral blood (PB) samples were obtained from patients enrolled in the SENTAD-COVID Study (ClinicalTrials.gov Reference: NCT04473170). hPBSCs cocktails (n=15) were provided by the Cells Processing Laboratory of Abu Dhabi Stem Cells Center, and were nebulized by three different methods of nebulization: compressor (jet), ultrasonic, and mesh. Our results reported that nucleated CD45(dim) cell count was significantly lower after the three nebulization methods, but nucleated CD45 - cells show a significant decrease only after mesh nebulization. Mesh-nebulized samples had a significant reduction in viability of both CD45(dim) and CD45 cells. Conclusions: This study provides evidence that stem cells derived from PB of COVID-19 patients can be nebulized without substantial loss of cell viability, cell count, and morphological changes using the compressor nebulization. Therefore, we recommend compressor nebulizers as the preferable procedure for hPBSCs delivery to the respiratory airways in further clinical settings.
Most epithelium tissues continuously undergo self-renewal through proliferation and differentiation of epithelial stem cells (known as homeostasis), within a specialized stem cell niche. In highly innervated epithelium, peripheral nerves compose perineural niche and support stem cell homeostasis by releasing a variety of neurotransmitters, hormones, and growth factors and supplying trophic factors to the stem cells. Emerging evidence has shown that both sensory and motor nerves can regulate the fate of epithelial stem cells, thus influencing epithelium homeostasis. Understanding the mechanism of crosstalk between epithelial stem cells and neurons will reveal the important role of the perineural niche in physiological and pathological conditions. Herein, we review recent discoveries of the perineural niche in epithelium mainly in tissue homeostasis, with a limited touch in wound repair and pathogenesis.
Cancer stem cells (CSCs) are a unique population of cells found within tumors that are able to self-renew, restore the original heterogeneity of a tumor following treatment, and show increased tumorigenic potential when compared to other cancer cells. It is thought that they are responsible for the recurrence of tumors as well as the resistance to treatment that is seen clinically. CSCs are known to be involved in head and neck cancer (HNCs) specifically, as evidence for their existence can be found in head and neck squamous cell carcinoma (HNSCC), mucoepidermoid carcinoma (MEC), and adenoid cystic carcinoma (ACC), among others. Here, findings from various approaches to identifying and targeting CSCs and their downstream effectors in HNC are summarized, with an emphasis on recent advancements. Prognostic and therapeutic markers are discussed for each specific type of HNC, and novel treatment strategies and current clinical trials involving CSCs are detailed as well. The information provided here is intended to further the research on this important topic and lead to clinical impact in the battle against HNC.
BACKGROUND:The recent newly appeared Coronavirus disease (COVID-19), caused by an enveloped RNA virus named "severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)", is associated with severe respiratory morbidity and mortality. Recent studies have shown that lymphopenia and a cytokine mass release represent important pathogenic features, with clinical evidence of dyspnea and hypoxemia, often leading to acute respiratory distress syndrome (ARDS), in severely ill patients, with a high death toll. Currently, stem cells are actively being investigated for their potential use in many "untreatable" diseases. In this regard and in particular, Mesenchymal Stem Cells (MSC), due to their intrinsic features, including either ability to impact on regulation of the immune system, or association with both anti-viral and anti-inflammatory properties, or potential for differentiation into several cell lineages, have become a promising tool for cell and molecular-based therapies. On this background, we wished to explore whether human umbilical cord-derived mesenchymal stem cells (hUCMS) would represent a potential viable therapeutic approach for the management of critically ill COVID19 patients.METHODS:We tested the hUCMS effects on peripheral blood mononuclear cell (PBMCs) retrieved from patients with COVID19 (Ethical Committee CEAS Umbria, Italy CER N°3658/20 7, May, 2020), both as free cell monolayers and after envelopment in sodium alginate microcapsules. Both cell systems, after priming with IFN-γ, proved able to produce several immunomodulatory molecules such as IDO1 and HLAG5, although only the microencapsulated hUCMS were associated with massive and dose-dependent production of these factors.RESULTS:The microencapsulated hUCMS improved allo-suppression in mixed lymphocytes reactions (MLRs), while also blunting T helper 1 and T helper 17 responses, that are involved with the cytokine storm and greatly contribute to the patient death. Moreover, we observed that both free and microencapsulated hUCMS permitted 5 days survival of in vitro culture maintained PBMCs extracted from very ill patients.CONCLUSION:We have provided evidence that microencapsulated hUCMS in vitro, seem to represent a powerful tool to impact on several immune pathways, clearly deranged in COVID19 patients. Further study is necessary to begin in vivo assessment of this experimental system, upon determining both, the most appropriate time of the disease onset for intervention, and cell dosage/patient of our experimental product.
Cell therapies could be the future of medicine. Many centers worldwide consider the use of stem cells to treat certain conditions. Well, proper homing remains the challenge, which means the ability to target the cells to the targeted site. Intraoperative transplantation of stem cells can overcome the homing challenge. However, it could be a double-edged sword, if a proper technique was not conducted. In this comment, a practical example of that is presented, where the use of stem cells in the vascular and neurovascular surgeries shows a promising potential, but the way in which the cells are processed and introduced is a critical step that should be given a lot of attention.
COVID-19 is a pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which caused deaths of more than 300.000 people around the world within the first few months of 2020. SARS-CoV-2 uses ACE2 receptors to infect respiratory system cells and may cause pneumonia and severe lung damage. The virus can also spread other organs rapidly via ACE2 expressing endothelial cells and cause coagulopathy, and further damage to the organs. Another and probably more harmful effect of the virus is the overreaction of the immune system leading to hyperinflammation causing multiple organ failure and death. Therefore COVID-19 can be considered as a viral infection causing auto-immune disorders. Currently, no vaccine or effective pharmacological treatment established for the disease. On the other hand, Mesenchymal Stem Cells (MSCs) possess anti- inflammatory and immune-regulatory effects along with their regenerative abilities. In this article, we thoroughly evaluate the COVID-19 pandemic and the damage mechanisms on the cellular level which can be ameliorated with the cellular therapies. We also gathered previous and ongoing stem cell clinical trial data from diseases with similar symptoms. All these accumulated data and current clinical trial results indicate that the cellular therapies could be the most effective treatment option for COVID-19 patients to ameliorate the damaged tissues and save lives. © Nova Science Publishers, Inc.
BACKGROUND Autism spectrum disorders [ASD] is a lifelong disability mainly affecting the development, communication, social interaction and behavior of an individual. Cell transplantation is emerging as a potential therapeutic strategy for ASD. Our previously published proof of concept study showed beneficial effects of cell transplantation in ASD. This study shows effect of cell transplantation in a larger sample size of ASD patients. METHODS 254 patients diagnosed with ASD on DSM V criteria were enrolled in this open label non-randomized study. The intervention included intrathecal transplantation of autologous bone marrow mononuclear cells and neurorehabilitation. On mean follow up of 7.50 months, percentage analysis was performed on all symptomatic changes. Changes in outcome measures, Indian Scale for Assessment of Autism [ISAA] and Childhood Autism Rating Scale [CARS], were analyzed statistically using Wilcoxon Signed-Rank Test. Comparative analysis of Positron Emission Tomography [PET CT] scan brain, performed before and 6 months after intervention, was done in 86 patients to monitor the outcome at cellular level. Change in the standardized uptake values was statistically evaluated using T-Test [P≤0.05]. RESULTS Improvements were observed in eye contact, attention and concentration, hyperactivity, sitting tolerance, social interaction, stereotypical behavior, aggressiveness, communication, speech, command following and self-stimulatory behavior. Statistically significant improvement was observed in scores of ISAA and CARS after intervention. A significantly better outcome of the intervention was found in patients at younger age and with shorter duration of disease [<5 years from time of diagnosis]. 86 patients who underwent a repeat PET CT scan showed improved brain metabolism after intervention in areas which correlated to the symptomatic changes. No major procedure related adverse events were recorded. However, 5 patients, with history of seizure and abnormal EEG, had an episode of seizure which was managed using medications. Outcome of intervention in these patients was not affected by seizures as improvements were observed in them. CONCLUSION The results of this study indicate that autologous bone marrow mononuclear cells in combination with neurorehabilitation are a safe and effective treatment modality for ASD. It improves the quality of life of patients and helps them to integrate in mainstream lifestyle.
Introduction HspB5 (αB-crystallin) is known to be involved in a variety of cellular functions, including, protection of cells from oxidative damage and inhibiting apoptosis. Neural stem/progenitor cells (NSPCs) have significant therapeutic value, especially in the NSC/NPC transplantation therapy. However, the viability of the transplanted NSPCs remains low because of various factors, including oxidative stress. Objective The current investigation explored the possible role of HspB5 in the protection of mouse NSPCs (mNSPCs) against paraquat-induced toxicity. Methods The recombinant human HspB5 was expressed in E.coli and was purified using gel filtration and Ion-exchange chromatography. The biophysical characterization of HspB5 was carried out using DLS, CD, and Analytical Ultracentrifugation (SV); the chaperone activity of HspB5 was determined by alcohol dehydrogenase aggregation assay. We have subjected the mNSPCs to paraquat-induced oxidative stress and monitored the protective ability of HspB5 by MTT assay and Hoechst-PI staining. Furthermore, increase in the expression of the anti-apoptotic protein, procaspase-3 was monitored using western blotting. Results The recombinant HspB5 was purified to its homogeneity and was characterized using various biophysical techniques. The externally added FITC-labeled HspB5 was found to be localized within the cytoplasm of mNSPCs. Our Immunocytochemistry results showed that the externally added FITC-labeled HspB5 not only entered the cells but also conferred cytoprotection against paraquat-induced toxicity. The protective events were monitored by a decrease in the PI-positive cells and an increase in the procaspase-3 expression through Immunocytochemistry and Western blotting respectively. Conclusion Our results clearly demonstrate that exogenously added recombinant human HspB5 enters the mNSPCs and confers protection against paraquat toxicity.
Background: In bone tissue engineering, biphasic calcium phosphate (BCP) with different hydroxyapatite (HA)/s-tricalcium phosphate (s-TCP) ratios can be combined with regeneration-competent stem cells, and bioscaffolds like fibrin that trigger neovascularization. We have shown recently that human adipose stem cells (hASCs) on BCP with a HA/s-TCP ratio of 20/80 (BCP20/80) incorporated in fibrin gel show enhanced osteogenic and/or vasculogenic differentiation potential compared to BCP with a HA/s-TCP ratio of 60/40 (BCP60/40) in vitro. A hypoxic microenvironment for the cells might occur in these hASC-seeded BCP-based composites after implantation in vivo. This limits oxygen supply which is essential for successful bone tissue engineering. Objectives: Here we aimed to test the effect of hypoxia on osteogenic and/or vasculogenic differentiation of hASC-seeded BCP60/40 or BCP20/80 scaffolds in fibrin gels as well as fibrin gel degradation. Methods: BCP60/40-based composites and BCP20/80-based composites were cultured under normoxia (20% O2) or hypoxia (1% O2) for 12 days, and total DNA content, alkaline phosphatase activity, nitric oxide production, vascular endothelial growth factor production, and fibrin gel degradation were assessed during culture. Results: Hypoxia similarly decreased total DNA content at day 7 (1.3-fold) and 12 (1.2-fold) in both composites. It also decreased alkaline phosphatase activity at day 5 (5.0 and 4.7-fold), day 7 (4.5 and 6-fold), and 12 (7.1 and 6.8-fold) in BCP60/40-based composites and BCP20/80-based composites. Hypoxia similarly increased vascular endothelial growth factor production at day 5 (3.9-fold) and day 7 (2.6-fold) by both BCP-based composites. Hypoxia did not affect nitric oxide production and fibrin gel degradation in both BCP-based composites at all-time points. Conclusion: Hypoxia decreased osteogenic differentiation but enhanced vasculogenic differentiation of cultured BCP-based composites. These in vitro results implicate that cell-seeded BCP-based composites implanted in vivo, might enhance vascular endothelial growth factor production resulting in sprouting and tube formation leading to increased survival of cells in these composites, and stimulation of bone formation.
The combined EVOP-MSCs is a therapeutic technique that should be soon applied in the practice of solid organ transplants. However, certain remarks should be considered on the pre-clinical levels before taking the studies further into the clinical levels. Although the present report will focus on the lung transplant, the ideas and the remarks are also to be considered for all other solid organ transplants, such as heart, liver and kidney.
Stem cells are self-renewing and undifferentiated cell types that can be differentiate into functional cells. Stem cells can be classified into two main types based on their source of origin: Embryonic and Adult stem cells. Stem cells also classified based on the range of differentiation potentials into Totipotent, Pluripotent, Multipotent, and Unipotent. Multipotent stem cells have the ability to differentiate into all cell types within one particular lineage. There are plentiful advantages and usages for multipotent stem cells. Multipotent Stem cells act as a significant key in procedure of development, tissue repair, and protection. Multipotent Stem cells have been applying in treatment of different disorders such as spinal cord injury, bone fracture, autoimmune diseases, rheumatoid arthritis, hematopoietic defects, and fertility preservation.
OBJECTIVE:To report the safety and therapeutic effectiveness of application of concentrated bone marrow aspirate in three bedridden patients with weakness in both legs, and monitor potential improvement in neurological outcomes.DESIGN:Case report. Intervention: Five infusions of 3x108 mononuclear cells were administrated with 12 week intervals. Bone marrow (240ML) were obtained from the posterior superior iliac spine and Bone marrow mononuclear cells were enriched by standard manual close method under aseptic condition.RESULTS:During the follow-up study of one year after stem cell implantation, the conditions of all three patients were improved and were confirmed by physical assessment, muscle charting and Electromyography (EMG). One year after stem cell implantation patients who were bedridden before treatment could sit without support and walk with support up to 200 feet at a stretch.CONCLUSION:The local application of a cocktail of regenerative cell population found in an MNC fraction of bone marrow was safe and effective in improving quality of life and muscle strength in ALS patients. This case opens the need for further investigations on Autogenic stem cell transplant therapies for MND disease.
Cicatricial tissue, being the local center of sclerosis, replaces the wound or focus of cell death. Scarring is caused by various types of injuries, including operations, as well as by a number of diseases. Scarring often culminates in the formation of strictures and other complications. Integrated stimulation of regeneration that takes the role of the immune system into account, in conjunction with the prescription of enzyme preparations possessing proteolytic activity, can be used to reduce the severity of sclerosis of damaged tissues.
With age the quantity of pluripotent stem cells gradually decreases. It leads to violation of renewal of tissues, including tissues of endocrine organs, at people over 35-40 years old. Artificial formation of the chimeral individual may be used for recovery of the pool of pluripotent stem cells in patients older than 40-50 years old. Transfusions of mononuclear fraction of peripheral blood procured from young donors 18-23 years old with the same blood groups and sex as the recipient (patent of the Russian Federation № 2350340), allows people over 40 years old to reestablish the pool of pluripotent stem cells, the process of tissue renewal and the production of sex hormones, and can also be seen as a promising way to reduce biological age, while providing a significant prolongation of life and while maintaining a high quality of life. Transfusions of mononuclear fraction of peripheral blood are required to be carried out multiple times before the restoration of the numerical strength of the recipients' pool of pluripotent stem cells is complete. The effectiveness of regeneration reconstitution in individuals older than 40 years old upon receiving transfusions of allogeneic pluripotent stem cells depends on the difference in age between the recipient and the young donor. When there is a major difference in age between young donors and recipients over 40 years old, the proliferative potential of pluripotent stem cells of donors (their ability to maintain the number of own pool) is higher than the proliferative potential of the recipient. In response to the formation of colony-stimulating growth factors, this leads to the dominance of transfused and formed colonies in the bone marrow of the donor's pluripotent stem cells over the analogous cells of recipients when renewing all of their tissues. The latter occurs mainly due to the donors' stem cells.
The majority of populations of differentiated cells are subject to renewal. Progenitor cells (cells-predecessors) and differentiated cells, having started the differentiation pathway or having finished it, can divide a limited number of times and are not capable of ensuring tissue regeneration during the whole period of ontogenesis. Renewal of tissues over such a long period is impossible without the participation of a specialized system which is responsible for regeneration. The given system is represented by pluripotent stem cells. Pluripotent stem cells, which conduct regeneration of all body tissues during ontogeny, are formed during implementation of the development program of the fertilized ovum, along with the formation of tissues and organs of the new organism. Being a separate direction of differentiation of embryonic cells, pluripotent stem cells are not embryonic cells. The immune system takes part in the formation of tissue-specific receptors among pluripotent stem cells. The latter remain pluripotent until the formation of tissue-specific receptors in them, and become committed (tissue-specific stem cells) after the formation of such receptors. Committed stem cells (tissue-specific stem cells) that migrate through the extracellular matrix replenish the progenitor cells of all tissues. Mesenchymal stem cells are the precursors of fibroblasts, and they only create conditions in the extracellular matrix for the migration and differentiation of committed (tissue-specific) stem cells in the places of cell death.
