Stem Cell-based Treatments Research Articles

Analyzing the Current Umbilical Cord-derived Mesenchymal Stem Cell Secretome Evidence for Erectile Dysfunction Management

Erectile dysfunction (ED) impacts millions of men, especially older men, and current treatment options, including tadalafil, phosphodiesterase type 5 inhibitors, and short-acting testosterone, are ineffective. This necessitates the immediate development of effective alternative ED treatments. In recent years, attention has been drawn to the secretome of umbilical cord-derived mesenchymal stem cells (UC-MSCs) due to its anti-inflammatory and immunomodulatory properties, which can reduce inflammation and promote tissue repair. The UC-MSCs secretome contains numerous growth factors, such as vascular endothelial growth factor, insulin-like growth factor 1 (IGF-1), and basic fibroblast growth factor (bFGF), which are essential for promoting endothelial cell proliferation and penile blood flow. This review seeks to examine the existing evidence on the use of stem cells, with a focus on UC-MSCs secretome, as a potential treatment modality for erectile dysfunction (ED). By reviewing the PubMed, Google Scholar, and Scopus databases, a comprehensive narrative review was conducted. Included among the search queries were "erectile dysfunction," "stem cells," "mesenchymal stem cells," "umbilical cord," and "secretome." Only research published in English within the past decade was included in the analysis. The findings indicate that the secretome of UC-MSCs has promise for treating ED. The secretome is composed of growth factors, cytokines, and other bioactive compounds that promote tissue repair and regeneration via paracrine effects on adjacent cells. The administration of UC-MSCs improved erectile function, penile blood flow, and smooth muscle content. In addition, discarded UC-MSCs serve as a cost-effective and copious source of ethically acceptable and immunogenic UC-MSCs with low immunogenicity. The secretome of UC-MSCs offers a potential therapeutic strategy for treating erectile dysfunction. However, further preclinical and clinical research must be done to determine the safety and efficacy of stem cell-based treatments for erectile dysfunction.

The Safety and Efficacy of Mesenchymal Stem Cells in the Treatment of Type 2 Diabetes- A Literature Review.

Type 2 diabetes (T2D) is the most common type of diabetes, affecting 6.28% of the population worldwide. Over the decades, multiple therapies and drugs have been developed to control T2D, but they are far from a long-term solution. Stem cells are promising as novel regenerative treatments, especially mesenchymal stem cells (MSCs), which are highly versatile in their regenerative and paracrine capabilities and characteristics. This makes them the most commonly used adult stem cells and ideal candidates to treat diabetes. To assess the safety and efficacy of mesenchymal stem cells (MSCs) in treating Type 2 diabetes (T2D) in humans. Mesenchymal stem cell-based treatments were studied in 262 patients. A total of 6 out of 58 trials fit our inclusion criteria in the last five years. The treatment of patients with MSCs reduced the dosage of anti-diabetic drugs analyzed over a follow-up period of 12 months. The effective therapy dosage ranged from 1×106 cells/kg to 3.7×106 cells/kg. After treatment, HbAc1 levels were reduced by an average of 32%, and the fasting blood glucose levels were reduced to an average of 45%. The C-peptide levels were decreased by an average of 38% in 2 trials and increased by 36% in 4 trials. No severe adverse events were noted in all trials. This analysis concludes that MSC treatment of type 2 diabetes is safe and effective. A larger sample size is required, and the trials should also study the effect of differentiated MSCs as insulin-producing cells.

The potential therapeutic role of extracellular vesicles in critical-size bone defects: Spring of cell-free regenerative medicine is coming.

In recent years, the incidence of critical-size bone defects has significantly increased. Critical-size bone defects seriously affect patients' motor functions and quality of life and increase the need for additional clinical treatments. Bone tissue engineering (BTE) has made great progress in repairing critical-size bone defects. As one of the main components of bone tissue engineering, stem cell-based therapy is considered a potential effective strategy to regenerate bone tissues. However, there are some disadvantages including phenotypic changes, immune rejection, potential tumorigenicity, low homing efficiency and cell survival rate that restrict its wider clinical applications. Evidence has shown that the positive biological effects of stem cells on tissue repair are largely mediated through paracrine action by nanostructured extracellular vesicles (EVs), which may overcome the limitations of traditional stem cell-based treatments. In addition to stem cell-derived extracellular vesicles, the potential therapeutic roles of nonstem cell-derived extracellular vesicles in critical-size bone defect repair have also attracted attention from scholars in recent years. Currently, the development of extracellular vesicles-mediated cell-free regenerative medicine is still in the preliminary stage, and the specific mechanisms remain elusive. Herein, the authors first review the research progress and possible mechanisms of extracellular vesicles combined with bone tissue engineering scaffolds to promote bone regeneration via bioactive molecules. Engineering modified extracellular vesicles is an emerging component of bone tissue engineering and its main progression and clinical applications will be discussed. Finally, future perspectives and challenges of developing extracellular vesicle-based regenerative medicine will be given. This review may provide a theoretical basis for the future development of extracellular vesicle-based biomedicine and provide clinical references for promoting the repair of critical-size bone defects.

Development and Validation of Type 2 Diabetic Zebrafish Model for Cell-Based Treatments.

Diabetes mellitus can be categorized as one of the prolonged metabolic disorders that are associated with inappropriately elevated blood glucose levels. Among the subgroups of this disease, type 2 diabetes accounts for the most patients. Although pharmaceutical and non-pharmaceutical treatments have been employed to control the progression of the disease, as with any treatment approach, both therapeutic approaches are associated with side effects and challenges. Nowadays, the emergence of treatment methods based on stem cells has attracted the attention of researchers in order to treat diabetes fundamentally and provide a long-term solution. Since there are still blind spots regarding the positive and negative effects of these types of treatments, animal studies can give researchers a detailed insight into the effects of stem cell-based treatments. Recently, zebrafish has been proposed as a valuable animal model due to its outstanding genetic and physiological characteristics in biomedical studies including diabetes. Hereupon, in this protocol, the development and validation of type 2 diabetic zebrafish model for cell-based treatments have been explained.

Convergence of human and veterinary medicine: leveraging canine naturally occurring neurological disorders to develop regenerative treatments.

Convergence of human and veterinary medicine: leveraging canine naturally occurring neurological disorders to develop regenerative treatments.

Stem Cells Therapy for Diabetes Mellitus Type 1. An Update on Safety and Outcomes

Type 1 diabetes mellitus (T1DM) is the most prevalent chronic autoimmune illness in children and young adults. It is defined by the loss of pancreatic cells, which causes the body to produce insufficient amounts of insulin and lead to hyperglycemia. Patients with T1DM have a great chance of recovery with stem cell therapy. There have been advancements in stem cell-based therapies for T1DM with the development of research on stem cell treatment for a variety of conditions. Before stem cell therapy for diabetic patients is clinically viable, there are still a lot of unresolved problems. In this review, we highlight recent developments in stem cell-based treatments for T1DM as well as methods for creating insulin-producing cells (IPCs) from various precursor cells. The aim of this study is to investigate the safety and outcomes of stem cells therapy for T1DM.

Current overview on stem cells in dentistry

In recent times, stem cell therapy has developed as an advanced and much more promising scientific research topic, and also evoked great expectations in development of new treatment modalities. The two crucial properties of stem cells i.e., the capacity to self-regenerate for a long-period without senescence and pluripotency, the ability to divide into one or more types of specialized cells, makes it a very emerging and demanding tool of tissue engineering and regenerative medicine. The aim of stem cell-based treatments is to restore normal anatomy and function of damaged teeth or their components through a regenerative process. The goals of regenerative dentistry include regeneration of pulp tissues, continued root formation, assisted transplantation and replantation, root bioengineering, reconstruction of periodontal tissue, and tissue engineering of the pulp-dentin complex. In order to obtain stem cells from dental tissue, it is necessary to establish appropriate methods for obtaining, isolating, culturing, and replicating stem cells. One of the most commonly stored stem cells is SHEDs. This is because they are readily available and similar to cord blood cells. SHED banking is not subject to the same ethical constraints as embryonic stem cells and provides individuals and their immediate family with an autologous source of stem cells. New approaches should first be tested in subcutaneous or renal capsule implants, followed by confirmation of results in root canal models to identify problems and reduce costs.

Could stem cell study in space avail patients and researchers on Earth?

With a growing proportion of people that are 65 years and older, age-linked cases like stroke, cancer, mentality, and degenerative illness lead to an escalating health load in the world. Regenerative medicine researchers are frequently acting to progress stem cell-based remedies that could assist cure patients with these situations. However, stem cell-based treatments require great numbers of stem cells that are hard to produce. The outgrowth media utilized in modality cell cultures do not supply perfect growth conditions, and even if stem cell amplification is effective, it is usually a slow operation. This triggers it defying tolerating stem cells into the big numbers required for clinical implementations. Cell cultures in a laboratory on Earth cultivate in a single layer –a 2D design– as gravity causes precipitation and the culture medium pushes downward on the cells. As an outcome, scientists want a template or scaffold to boost the up growing tissue in 3D tissue engineering and regenerative medicine are strategic zones of concentrate for the International Space Station (ISS) Lab. In a weightless milieu as space, cells could display selectively unstrapped expansion and gather into congregation 3-D builds. This could open the prospect of “macro-tissues” –organs – may to be created from these 3-D cell structures. Beside, in the trust of concluding several of the mysteries of how stem cells expand, split and compose into tissues. Aspire to stem cell research to be the zone that could be progressed in microgravity. Hope for the ISS National Lab to fit as an entirely realistic feasible practical robust down-to-earth space laboratory for workable and potentially safe to grow mesenchymal stem cells (MSCs) for potential future clinical applications on Earth.

Adipose-derived mesenchymal stem cells reduced transient cerebral ischemia injury by modulation of inflammatory factors and AMPK signaling

Stem cell-based treatments have been recommended as a feasible therapy for stroke victims due to their potential for angiogenesis, neurogenesis, and synaptic plasticity. The intracellular mechanisms of stem cells against cerebral hypoperfusion are not well recognized. In this study, by releasing the clips, the reperfusion period was extended to 96 h, and two hours after cerebral ischemia, animals received adipose-derived MSCs. MSCs were isolated from the inguinal fat pads of rats and injected into two-vessel occlusion (2VO) rats 1 h after ischemia induction. Ninety-six hours after 2VO induction, behavioral and molecular tests were assessed. Adipose-derived MSCs treatment improves neurological scores, passive avoidance memory, and novel object recognition tests in the 2VO model compared to 2VO rats (P < 0.001). MSCs treatment decreased TNF-α (P < 0.01) and IL-6 (P < 0.01) and apoptotic factors (Bax/Bcl-2 ratio and caspase-3 level (P < 0.01)) compared with ischemic rats. MSCs treatment of ischemic rats could enhance Klotho-α and AMPK-α compared with ischemic rats (P < 0.001). The study disclosed that adipose-derived MSCs could improve neurological damage and memory deficits by reducing neuronal death in cerebral ischemia. Data proposed that adipose-derived MSCs inhibit pro-inflammatory factors such as IL-6 and TNF-α, consequently decreasing apoptosis in the hippocampus of CCAO rats. Besides, the Klotho-α and AMPK-α measurements found that MSCs might induce intracellular neuroprotective pathways via activation of Klotho-α/AMPK-α signaling.

Stem Cell Therapy for Myocardial Infarction: A Mini-Review

Stem cells are undifferentiated cells that can proliferate, regenerate, develop into differentiated cells, and produce a variety of tissues. Embryonic stem cells, adult or somatic stem cells, and pluripotent stem cells are the three types of stem cells. Another classification of stem cells is totipotent, multipotent, and unipotent cells. Stem cell treatment has the possibility of treating degenerative disorders, cancer, and the restoration of damaged tissues, all of which now have no or restricted medicinal alternatives. Myocardial infarction is a potentially fatal condition caused by the permanent loss of cardiomyocytes and a deterioration in the heart's blood-pumping capacity. Throughout the last two decades, stem cell-based treatments for myocardial infarction therapy have been researched with encouraging results. Traditional therapy for myocardial infarction slows disease development but has little effect on healing. Because of their ability to initiate de novo cardiogenesis, embryonic stem cells are thought to be a potential candidate for cardiac regeneration.&#x0D;

An Infodemic of Misinformation on Stem Cell Therapy Among the Population of Saudi Arabia: A Cross-Sectional Study

In recent years, the industry of unproven stem cell-based therapies has been on the rise around the globe, putting patients at great risk of potential harm. In this cross-sectional study, we aimed to assess the level of knowledge and awareness of the general public, including patients and/or their relatives, in Saudi Arabia on stem cell therapy and to assess the degree of willingness to try stem cell-based treatment options, should it be offered to them.MethodsA voluntary questionnaire of 16 questions was distributed randomly through social media outlets.ResultsIn the survey of this study, 2,030 individuals participated. A total of 1,292 (63.6%) stated that they would accept stem cell therapy or would recommend it to their friends and relatives. Alarmingly, 72.1% of participants were unaware that using unapproved stem cell-based treatments may lead to serious health complications including cancer. More than 20% believed that stem cell therapy is already approved for organ/tissue regeneration. Worryingly, 60.6% of the physicians and 56.4% of the medical students stated that they would recommend stem cell treatment for their patients.ConclusionsThere is a concerning spread of misinformation among the Saudi population, including physicians, regarding stem cell therapy. This calls for a targeted effort to raise awareness about the current status of stem cell treatment in the general public and among health care practitioners.

Co-Administration of Menstrual Blood-Derived Stem Cells and Remdesivir for the Treatment of Severe Coronavirus Disease 2019 (COVID-19) Induced Pneumonia: A Research Protocol

Introduction: Remdesivir (Veklury), a viral ribonucleic acid (RNA)-dependent RNA polymerase inhibitor designed by Gilead Sciences, has shown reductions in recovery time for coronavirus disease 2019 (COVID-19) patients, although its efficacy remains controversial. It has been proposed that combining remdesivir with immunomodulators may improve clinical efficacy. Mesenchymal stem cells (MSCs) exert immunomodulatory properties, which resolve COVID-19-induced pneumonia in early-phase trials. Menstrual blood-derived stem cells (MenSCs) present a novel MSC source, superior in availability, proliferative ability, and ethicality than traditional stem cell sources. This study aims to investigate the efficacy of remdesivir-MenSC combination therapy in resolving severe COVID-19-induced pneumonia. Methods: A randomized, double-blind, controlled study will be performed to assess two primary endpoints: time of recovery, defined as no longer requiring ongoing medical care, and normalization of the immune system, defined as the change in the concentration of key cytokines from baseline. Safety will also be measured as the frequency of treatment-related adverse events (AE). The study will aim to recruit 400 eligible subjects, aged 18 to 75, hospitalized with severe COVID-19, and they will be assigned to either receive intravenous (IV) infusions of MenSCs and remdesivir, or receive only remdesivir. A stratified log-rank test will be conducted to compare the time of recovery between study arms, with stratification by disease severity (baseline ordinal score). Two-way repeated measures ANOVA will be used to compare cytokine levels over time in the treatment group compared to the control group. Discussion: We expect remdesivir-MenSC combination therapy to surpass remdesivir in clinical efficacy and safety profile by improving clinical status, lowering duration of hospitalization, reducing mortality, and lowering the incidence of treatment-related AEs. Conclusion: Investigating this promising approach is an essential step in determining the feasibility of stem cell-based treatments in improving current COVID-19 therapeutics and patient outcomes. In particular, evaluating the clinical potential of MenSCs may provide insight into future therapeutic research as the literature has shown that MenSCs are superior to traditional MSC sources.

Mesenchymal stem cell-based treatments for COVID-19: status and future perspectives for clinical applications.

As a result of cross-species transmission in December 2019, the coronavirus disease 2019 (COVID-19) became a serious endangerment to human health and the causal agent of a global pandemic. Although the number of infected people has decreased due to effective management, novel methods to treat critical COVID-19 patients are still urgently required. This review describes the origins, pathogenesis, and clinical features of COVID-19 and the potential uses of mesenchymal stem cells (MSCs) in therapeutic treatments for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients. MSCs have previously been shown to have positive effects in the treatment of lung diseases, such as acute lung injury, idiopathic pulmonary fibrosis, acute respiratory distress syndrome, lung cancer, asthma, and chronic obstructive pulmonary disease. MSC mechanisms of action involve differentiation potentials, immune regulation, secretion of anti-inflammatory factors, migration and homing, anti-apoptotic properties, antiviral effects, and extracellular vesicles. Currently, 74 clinical trials are investigating the use of MSCs (predominately from the umbilical cord, bone marrow, and adipose tissue) to treat COVID-19. Although most of these trials are still in their early stages, the preliminary data are promising. However, long-term safety evaluations are still lacking, and large-scale and controlled trials are required for more conclusive judgments regarding MSC-based therapies. The main challenges and prospective directions for the use of MSCs in clinical applications are discussed herein. In summary, while the clinical use of MSCs to treat COVID-19 is still in the preliminary stages of investigation, promising results indicate that they could potentially be utilized in future treatments.

Adipose Stem Cell-Based Treatments for Wound Healing.

Wound healing is one of the most complex physiological regulation mechanisms of the human body. Stem cell technology has had a significant impact on regenerative medicine. Adipose stem cells (ASCs) have many advantages, including their ease of harvesting and high yield, rich content of cell components and cytokines, and strong practicability. They have rapidly become a favored tool in regenerative medicine. Here, we summarize the mechanism and clinical therapeutic potential of ASCs in wound repair.

Therapeutic angiogenesis in Buerger's disease: reviewing the treatment landscape.

A review of available and emerging treatments for improving blood flow and wound healing in patients with Buerger's disease, a rare disorder of blood vessels Buerger's disease is a rare disorder of the small- and medium-sized blood vessels in the arms and legs that almost exclusively develops in young smokers. Buerger's disease causes inflammation in arteries and veins, which leads to blockage of these vessels and reduces blood flow to and from the extremities. Decreased blood flow to the arms and legs can lead to development of nonhealing wounds and infection for which some patients may eventually require amputation. Unfortunately, traditional medical and surgical treatments are not effective in Buerger's disease, so other methods for improving blood flow are needed for these patients. There are several different ways to stimulate new blood vessel formation, both in humans and animal models. The most common treatments involve injection of DNA or viruses that express genes related to blood vessel formation or, alternatively, stem cell-based treatments that help regenerate blood vessels and repair wound tissue. This review explores how safe and effective these various treatments are and describes recent research developments that may lead to better therapies for patients with Buerger's disease and other vascular disorders.

Safety and efficacy of bone marrow derived-mesenchymal stem cells transplantation in patients with amyotrophic lateral sclerosis.

Stem cell-based treatments have emerged as potentially effective approaches to delay the progression of amyotrophic lateral sclerosis (ALS). This study was designed as a single-center, prospective, and open-label study without a placebo control group to assess the safety and efficacy of concurrent intrathecal (IT) and intravenous (IV) administration of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) in patients with ALS. Autologous BM-MSCs were isolated and expanded under standard conditions. Fifteen patients were neurologically examined before BM-MSCs transplantation (1 × 10 6 cells/kg BW) to evaluate the rate of pre-treatment disease progression. To assess the safety and efficacy, patients were examined at 1, 3, and 6 months following the treatment with BM-MSCs. Adverse reactions were assessed, and the clinical outcome was determined by the evaluation of the ALS functional rating scale-revised (ALSFRS-R) and forced vital capacity (FVC). No serious adverse reaction was observed after combined IT and IV administration of BM-MSCs. The mean ALSFRS-R and FVC values remained stable during the first 3 months of the treatment. However, a significant reduction in ALSFRS-R and FVC levels was observed in these patients 6 months after BM-MSCs administration. Our study revealed that the concurrent IT and IV application of BM-MSCs in patients with ALS is a safe procedure. Furthermore, our data indicate a temporary delay in the progression of ALS after a single combined IT and IV administration of BM-MSCs. Further studies are required to explore if the repeated applications of BM-MSCs could prolong survival and delay the progression of ALS.

Potential therapeutic applications of mesenchymal stem cells for the treatment of eye diseases.

Stem cell-based treatments have been extensively explored in the last few decades to develop therapeutic strategies aimed at providing effective alternatives for those human pathologies in which surgical or pharmacological therapies produce limited effects. Among stem cells of different sources, mesenchymal stem cells (MSCs) offer several advantages, such as the absence of ethical concerns, easy harvesting, low immunogenicity and reduced tumorigenesis risks. Other than a multipotent differentiation ability, MSCs can release extracellular vesicles conveying proteins, mRNA and microRNA. Thanks to these properties, new therapeutic approaches have been designed for the treatment of various pathologies, including ocular diseases. In this review, the use of different MSCs and different administration strategies are described for the treatment of diabetic retinopathy, glaucoma, and retinitis pigmentosa. In a large number of investigations, positive results have been obtained by in vitro experiments and by MSC administration in animal models. Most authors agree that beneficial effects are likely related to MSC paracrine activity. Based on these considerations, many clinical trials have already been carried out. Overall, although some adverse effects have been described, promising outcomes are reported. It can be assumed that in the near future, safer and more effective protocols will be developed for more numerous clinical applications to improve the quality of life of patients affected by eye diseases.

Current Stem Cell Research Status on Hepatic and Pulmonary Sclerosis in COVID-19

Since 2019, Coronavirus Disease (COVID-19) has changed the concept of systemic sclerosis caused by viral infectious diseases. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative organism of COVID-19, has infected more than 1.36 billion people in 188 countries, and nearly 2.29 million have died. Although we have rapidly developed vaccines against COVID-19, the struggle to treat COVID-19 patients who exhibit complicated multiple organ sclerosis has continued ever since. Studies have reported that preexisting liver disease in 3-8% of patients increases metabolic dysfunction and mortality by 4-6-fold in association with the severity of COVID-19. Moreover, both confirmed and cured COVID-19 patients have been reported to develop pulmonary fibrosis, which is often related to poor prognosis of the complications. Therefore, in the present study, we summarize the possible mechanisms underlying the development of hepatic and pulmonary fibrosis caused by SARS-CoV-2 infection, based on recently published data. Furthermore, since stem cell-based treatments have been developed as a novel approach to treat COVID-19 patients with Systemic Sclerosis (SS), we discuss the implementation of stem cell-based treatments as a powerful regenerative tool owing to their notable immunomodulatory and anti-fibrotic effects.

VIVID: In Vivo End-to-End Molecular Communication Model for COVID-19.

As an alternative to ongoing efforts for vaccine development, scientists are exploring novel approaches to provide innovative therapeutics, such as nanoparticle- and stem cell-based treatments. Thus, understanding the transmission and propagation dynamics of coronavirus inside the respiratory system has attracted researchers’ attention. In this work, we model the transmission and propagation of coronavirus inside the respiratory tract, starting from the nasal area to alveoli using molecular communication theory. We performed experiments using COMSOL, a finite-element multiphysics simulation software, and Python-based simulations to analyze the end-to-end communication model in terms of path loss, delay, and gain. The analytical results show the correlation between the channel characteristics and pathophysiological properties of coronavirus. For the initial 50% of the maximum production rate of virus particles, the path loss increases more than 16 times than the remaining 50%. The delayed response of the immune system and increase in the absorption of virus particles inside the respiratory tract delay the arrival of virus particles at the alveoli. Furthermore, the results reveal that the virus load is more in case of asthmatic patients as compared to the normal subjects.

Bioactive micropatterned platform to engineer myotube-like cells from stem cells

Skeletal muscle has the capacity to repair and heal itself after injury. However, this self-healing ability is diminished in the event of severe injuries and myopathies. In such conditions, stem cell-based regenerative treatments can play an important part in post-injury restoration. We herein report the development of a bioactive (integrin-β 1 antibody immobilized) gold micropatterned platform to promote human mesenchymal stem cell (hMSC) differentiation into myotube-like cells. hMSCs grown on bioactive micropattern differentiated into myotube-like cells within two weeks. Furthermore, the up-regulation of myogenic markers, multi-nucleated state with continuous actin cytoskeleton and the absence of proliferation marker confirmed the formation of myotube-like cells on bioactive micropattern. The prominent expression of elongated integrin-β 1 (ITG-β 1) focal adhesions and the development of anisotropic stress fibers in those differentiated cells elucidated their importance in stem cell myogenesis. Together, these findings delineate the synergistic role of engineered cell anisotropy and ITG-β 1-mediated signaling in the development of myotube-like cells from hMSCs.