by admin | May 17, 2023 | Stem Cell Therapy, Kidney Disease, Mesenchymal Stem Cells, Stem Cell Research
Ischemic kidney diseases are serious health issues that lead to irreversible loss of kidney function and are commonly associated with high rates of mortality and morbidity. Many of the conditions captured under the term ischemic kidney disease occur as a result of decreased glomerular filtration rate (GFR) caused by vasoconstriction or loss of autoregulation. Ischemic kidney disease, or ischemic renal disease, is a contributing factor anywhere between 6% – 27% of end-stage kidney disease and is most common among patients 50 years old or older.
The progression of these types of kidney diseases is often multifaceted and involves complex hormonal-immunological cellular interactions. Since ischemic kidney disease often involves damage that occurs to many different types of cells, the conditions have often been demonstrated to be resistant to conventional therapy.
Considering mesenchymal stem cells (MSCs) provide renal protection, their anti-inflammatory and immunomodulatory properties are of interest in an effort to better understand how they can be therapeutically used to treat and prevent acute kidney ischemia (AKI).
In this review, Zhu et al. examine recent progress in the use of MSC to prevent kidney diseases, with a specific focus on chronic ischemic kidney disease (CIKD).
When used to treat CIKD, MSCs have been found to achieve renal cellular repair in a number of different ways. Initially, and upon infusion, MSCs home to the injury site and release homing receptors, growth factors, and anti-inflammatory cytokines to the injury site. They also release similar microparticles that promote kidney repair through internalization in other cells, allowing for reduced intrarenal inflammation and the promotion of vascular regeneration.
Examining the results of clinical trials exploring the use of MSC to treat CIKD, and considering patients with diabetes mellitus often develop chronic kidney issues, including diabetic nephropathy (DN), the authors believe the beneficial application of the anti-inflammatory, antioxidant, and immunomodulating features of MSC could help in the treatment of DN.
While Zhu et al. highlights the potential of MSCs in the treatment of CIKD in this review, they also identify potential limitations, including the potential for MSCs to form teratoma or other tumors (to date, no direct evidence of kidney tumor formation has been reported) and exactly how long the effects of MSC on kidney protection will last. As a way to address both potential limitations, the authors recommend longer follow-up times to ensure all potential detrimental effects of MSC use in humans are known and accounted for.
The review concludes that while further studies are needed to discern the chief elements of their actions and to define the optimal type (tissue source, preconditioning), dose, and delivery route, MSCs demonstrate remarkable potential for future treatment of ischemic kidney disease.
Source: “Concise Review: Mesenchymal Stem Cell Treatment for Ischemic ….” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3795813/.
by admin | May 10, 2023 | Stem Cell Therapy, Mesenchymal Stem Cells, Multiple Sclerosis, Stem Cell Research
Multiple sclerosis (MS) is a progressive disease of the central nervous system (CNS) that occurs as a result of the body’s immune system attacking the protective sheath, or myelin, responsible for covering nerve fibers. Characterized by progressive nerve deterioration and damage of the nerve fibers, MS is currently estimated to affect nearly 600,000 adults in the United States.
While a specific cause of MS has not yet been determined, recent findings have suggested interactions between environmental and genetic factors as contributors to the susceptibility to MS.
Current pharmaceutical treatments for MS have demonstrated the ability to slow symptoms associated with MS but have not demonstrated the ability to treat or prevent the disease itself.
Recent studies have identified mesenchymal stem cells (MSCs) as having anti-inflammatory properties that could potentially be an effective therapy option for preventing or managing overactivity and self-antigen attacks by T cells and macrophages that are commonly associated with MS.
As part of this review, Alanazi et al. examined the most relevant clinical trials that utilized MSCs from a variety of sources as part of their investigation into the effectiveness of these stem cells as a potential therapy for MS.
MSCs are able to be easily isolated from multiple sources of the human body, including bone marrow, adipose tissue, umbilical cord, and the placenta. These stem cells have also demonstrated the ability to be expanded in culture media and to be safely utilized as autologous treatment without the risk of rejection.
Regardless of their source, MSCs, in general, have been demonstrated to be highly proliferative, capable of self-renewal, and have immunomodulatory and neurodegenerative effects. In addition, MSCs demonstrate the ability to differentiate and secrete anti-inflammatory factors that allow them to control the progress of autoimmune diseases, including MS.
After examining numerous clinical trials utilizing MSCs from a range of sources, the authors conclude that MSCs – regardless of their source – will all work on inhibiting CD4+ and CD8+ T cell activation, T regulatory cells (Tregs), and macrophage switch into the auto-immune phenotype.
While there are many good sources of MSCs, Alanazi et al. also conclude that previously conducted clinical trials demonstrate umbilical cord MSCs (UCMSCs) to be the best option for the management of Multiple Sclerosis for several reasons. These reasons include faster self-renewal than other MSCs, the ability to differentiate into three germ layers, and the observed ability to accumulate in damaged tissue or inflamed areas.
Additionally, and besides being one of the few MSC sources without ethical concerns, UCMSCs offer benefits from a practical standpoint The separation of MSCs from the umbilical cord is easy and painless, the number of cells collected per unit is high, UCMSC transfusion is not expensive, and UCMSCs have been shown to be very safe to use in this application.
Considering the information presented in this review, Alanazi et al. recommend the clinical use of UCMSCs for regenerative medicine and immunotherapy.
Source: “Mesenchymal stem cell therapy: A review of clinical trials for multiple ….” 23 Aug. 2022, https://pubmed.ncbi.nlm.nih.gov/36092509/.
by admin | May 3, 2023 | Stem Cell Therapy, COPD, Mesenchymal Stem Cells, Stem Cell Research, Umbilical Stem Cell
Chronic obstructive pulmonary disease (COPD) is an incurable and debilitating disease characterized by chronic and progressive inflammation that leads to small airway obstruction and emphysema.
According to the World Health Organization, COPD is the third leading cause of death and is responsible for an estimated 3.2 million deaths each year. Between 80 and 90% of all COPD cases are caused by exposure to cigarette smoke, meaning it is also one of the most preventable diseases.
In addition to the increased risk of death, COPD significantly affects the overall quality of life and is often associated with difficulty breathing, chronic cough, lack of energy, lung infections, lung cancer, and heart disease.
A number of stem-cell-based approaches to address this issue are currently being explored. In this study, Ridzuan et al. uses an animal model to assess the potential anti-inflammatory effects of human umbilical cord mesenchymal stem cell (hUC-MSC)-derived extracellular vesicles (EVs) in cases of COPD.
EVs are small membrane vesicles of multivesicular bodies that are released by a variety of cells, including MSCs. Studies have demonstrated EVs isolated from MSCs mimic the therapeutic effects of MSCs.
Over the course of this study, and to mimic the symptoms observed with COPD, rats were exposed to cigarette smoke for up to 12 weeks, followed by transplantation of hUC-MSCs or application of hUC-MSC-derived EVs.
At the conclusion of this study, Ridzuan et al. found that both the transplantation of hUC-MSCs and the application of hUC-MSC-derived EVs reduced peribronchial and perivascular inflammation, slowed alveolar septal thickening, and decreased the number of goblet cells. Both applications also improved the loss of alveolar septa in the lung of COPD rats and regulated multiple pathways commonly associated with COPD.
Ridzuan et al. conclude that hUC-MSC-derived EVs effectively reduce COPD-induced inflammation and could have the potential to be a therapy for the management of COPD.
The authors also concluded that the selected treatment methods decreased the above-described symptoms at comparable rates. While there are still limited data demonstrating the regenerative and the anti-inflammatory effects of MSC-EVs to mitigate the inflammation in COPD, further study is needed to fully understand the anti-inflammatory effects of MSC-EVs and to better understand the specific mechanisms of action of all contents of MSC-EVs as they relate to the potential future treatment of COPD.
Source: “Human umbilical cord mesenchymal stem cell-derived extracellular ….” 12 Jan. 2021, https://stemcellres.biomedcentral.com/articles/10.1186/s13287-020-02088-6.
by admin | Apr 5, 2023 | Mesenchymal Stem Cells, Stem Cell Research
Cigarette smoking continues to be the leading contributor to preventable disease and death in the United States, including cancer, heart disease, stroke, lung diseases, diabetes, and chronic obstructive pulmonary disease (COPD). Smoking cigarettes also increases the risk of tuberculosis, certain eye diseases, chronic pain, and problems of the immune system, including rheumatoid arthritis.
An abundance of clinical research has clearly shown the detrimental effects cigarette smoke has on nearly every area of the body. However, while assumed to be equally dangerous in its effect on stem cells, there is surprisingly little research exploring the negative implications of cigarette smoking on stem cells.
In this review, Nguyen et al. share findings of recent studies on the effects of cigarette smoking and nicotine on mesenchymal stem cells (MSCs), with a specific focus on dental stem cells.
With their ability to self-renew, develop into specialized cell types, and migrate to potential sites of injury, stem cells have demonstrated the potential to build every tissue in the body and have also demonstrated great potential for tissue regeneration and associated therapeutic uses.
As the potential benefits and weaknesses of stem cells continue to be discovered, researchers have found that cigarette smoking negatively impacts the abilities of stem cells while also limiting stem cell viability for transplantation and regeneration.
While there has been a recent decline in the percentage of U.S. adults who smoke, over 34 million U.S. adults continue to be regular cigarette smokers. Interestingly, research has demonstrated the concentration of nicotine to be significantly higher in saliva than in blood plasma following nicotine administration via cigarette, e-cigarette, and nicotine patch – in some cases measuring up to eight times higher concentrations. Considering this research, and considering the established detrimental effects of e-cigarette vapor – and presumably nicotine – on teeth and dental implants, the authors of this review hypothesized that there would be a similar effect when dental stem cells are exposed to cigarette smoke.
Reviewing the effect that cigarette smoke has on MSCs, the authors found that exposing MSCs to cigarette smoke extract (CSE) and nicotine impaired cell migration, increased early and late osteogenic differentiation markers, decreased cell proliferation, and significantly inhibited the ability of MSCs to differentiate to other types of cells.
Nguyen et al. reviewed research that determined cigarette smoke produced a negative impact on the proliferation and differentiation of dental pulp stem cells (DPSCs). Specifically, this research demonstrated a significantly higher depression of alkaline phosphatase (ALP) and osteocalcin (OC) genes in smokers when compared to nonsmokers. Additional studies found that smokers demonstrated reduced calcium deposition levels and production of ALP when compared to nonsmokers.
Cigarette smoke and nicotine were also found to negatively affect the migration capability of dental stem cells, slowing the migration rate by up to 12% in smokers while also producing a smaller reduction of scratch wound areas when compared to nonsmokers.
While there are not many studies directly comparing the effects of cigarette smoke and nicotine on MSCs and dental stem cells, the authors conclude that dental stem cells exhibit similar characteristics to bone marrow MSCs and that both of these types of stem cells demonstrate similar negative responses upon their exposure to nicotine.
While the authors call for further research to better understand the specific effects of cigarette smoke on dental stem cells, the authors conclude that the findings demonstrating similar responses to cigarette smoke and nicotine between dental stem cells and MSCs can be used to inform future dental stem cell studies. These findings will help dentists better identify which patients might be at an increased risk of poor healing in the oral cavity and if smoking cessation should be considered before undergoing any invasive or traumatic dental procedure, such as tooth extraction.
Source: Comparison of the effect of cigarette smoke on mesenchymal stem ….” https://journals.physiology.org/doi/10.1152/ajpcell.00217.2020.
by admin | Mar 17, 2023 | Mesenchymal Stem Cells, Stem Cell Research, Stem Cell Therapy
An estimated 100 million people in the U.S. have some form of acute or chronic liver disease. Many factors, including viral and bacterial infections, substance abuse, diabetes, and fat deposition, contribute to conditions that harm the liver.
Left untreated, these liver conditions often progress to more serious diseases that often require a liver transplant. Historically, a host of issues – including a low number of tissue donors, a high rate of tissue rejection, medicine-induced immunosuppression, and high associated medical costs – has limited access to, and the effectiveness of, liver transplantation as a viable solution.
Considering the limited options available for the successful treatment of liver disease, identifying alternative treatment options has become very important. Recently, the potential treatment of acute and chronic liver disease using regenerative medicine, also known as stem cell therapy, has garnered an increased amount of attention.
While a number of different types of stem cells have been used to treat liver disease, mesenchymal stem cells (MSCs) have been the most studied and successful in reducing the need for liver transplantation.
MSCs have been used to repair liver tissue through a number of different methods, including co-culturing with HSCs to reduce and prevent the progression of fibrosis and the proliferation of disease-causing cells through the production and secretion of specific inflammatory factors.
Treatment of liver disease with MSCs has also been shown to increase endothelial precursor cell proliferation while suppressing apoptosis in LSECs and hepatocytes, and by lowering serum transaminase enzyme levels. MSCs have also been shown to compensate for hepatocyte reduction resulting through liver-disease induced apoptosis by differentiating into hepatocyte-like cells.
Considering the observed role of MSCs in liver tissue repair and regeneration, Hazrati et al concluded that the use of MSCs induces the repair and regeneration of liver tissue through immune response modulation, differentiation into HLCs, increased proliferation and decreased apoptosis in hepatocytes, increased apoptosis and reduced function of HSCs and improve the function of LSECs.
The authors also point out that, as of publication, there were 61 active clinical trials using MSCs to treat a variety of liver-related diseases, including cirrhosis, fibrosis, and liver failure. The associated advantages of MSCs in the treatment of acute and chronic inflammatory liver disease include ease of isolation and culture, pluripotency, immunomodulatory and anti-inflammatory properties, extracellular signaling, and their ability to differentiate.
The authors conclude this review by summarizing the observed benefits of using MSCs, and specifically MSC-EVs to improve liver function and support the repair of damaged liver tissue. The authors also point out that while there have been numerous clinical trials using MSCs to treat liver disease, there have been no clinical trials performed on the use of MSC-EVs and call for additional research to investigate the long-term effects of treating liver disease with MSC-EVs.
Source: “Mesenchymal Stromal/Stem Cells and Their Extracellular Vesicles ….” https://www.frontiersin.org/articles/10.3389/fimmu.2022.865888/full.
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