by admin | Jun 28, 2023 | Mesenchymal Stem Cells, Stem Cell Research, Stem Cell Therapy
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, 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 | Jun 21, 2023 | Stem Cell Therapy, Regenerative Medicine, Stroke
Recent advances in medical accessibility, technology, and treatment have increased the average human life expectancy, while at the same time, increasing the risk for neurodegenerative diseases and other disorders – including stroke.
According to the CDC, nearly 800,000 people in the United States suffer a stroke each year, with 87% of these strokes being ischemic strokes. An ischemic stroke is a medical emergency that occurs when the blood supply to part of the brain is reduced or interrupted. Without the ability to deliver oxygen or nutrients, brain cells begin to die in a matter of minutes.
Even when identified and treated early, the lasting, long-term effects associated with stroke result in economic and social costs for patients, their families, and society in general. As an example, the CDC estimates that stroke-related costs, including those associated with healthcare and missed days of work, exceed $50 billion dollars in the U.S. each year.
While medical research continues to search for ways to prevent stroke by addressing underlying causes, primary stroke treatment continues to focus on managing stroke progression while also treating related symptoms.
Recently regenerative medicine, also known as stem cell therapy, along with rehabilitation therapy has been presented as an effective stroke treatment. In this review, Berlet, et al. explore the potential synergistic outcomes of stroke treatment observed when combining current advances in stem cell research with known stroke rehabilitation strategies. The authors also review research while considering the advantages and disadvantages of using the combination of stem cell transplantation and rehabilitation as a way to mitigate the devastating effects of stroke.
Combining stem cell treatment with rehabilitation therapy and outside strategies, such as an enriched environment (EE) may enhance functional stroke recovery and allow for an ideal long-term therapy for stroke patients. With the goal of enhanced brain plasticity, these therapies aim to introduce intrinsic or extrinsic stimuli to assist with the reorganization of the brain’s structure, functions, and connections.
The human brain has been demonstrated to be more plastic after experiencing an injury. With EE promoting improved stem cell survival and migration, and stem cell therapy creating the potential for an extended window of treatment, the combination is viewed as a potentially effective therapy when combined.
Preclinical experimentation has demonstrated stem cell therapies to be effective days after an ischemic stroke occurs, providing a very important window of time for critical stroke treatment to occur. While this is certainly promising information, the authors also point out that there has been a disappointing and frustrating disconnect between these preclinical findings and what is observed in clinical experimentation.
Considering this, the authors identify determining the optimal clinical stem cell route of administration, dosage, and timing as key areas of study to better understand – and maximize – the therapeutic potential of stem cells in the treatment of ischemic stroke.
While Berlet et al. calls for additional research into the ideal route of stem cell administration, type dosage, and timing to further confirm the efficacy of stem cell transplantation for the treatment of ischemic stroke, the authors conclude that the addition of stem cell therapy to rehabilitation has significant potential to create a conducive host microenvironment to facilitate the repair process.
Source: “Combination of Stem Cells and Rehabilitation Therapies for … – NCBI.” 6 Sep. 2021, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8468342/.
by admin | Jun 14, 2023 | Stem Cell Therapy, COPD, Regenerative Medicine
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease that causes obstructed airflow from the lungs. Affecting an estimated 15 million people in the United States alone, COPD is characterized by progressively worsening symptoms, including breathing difficulty, cough, mucus (sputum) production, and wheezing, and is most often the result of prolonged exposure to cigarette smoke.
Not just an issue for those in the U.S., COPD has been demonstrated to be a preventable and treatable global health challenge. With an estimated 3.5 million worldwide deaths attributed to COPD each year, the disease is currently the third leading cause of death.
While there have been medical advances in the treatment of COPD, these therapies focus primarily on symptomatic relief and not the reversal of lung function deterioration or improvement in patients’ quality of life.
Since stem cells are known to differentiate into a wide variety of cell types and have been previously used to regenerate lung parenchyma and airway structure, they are believed to be an evolving and promising therapeutic treatment option for those with COPD.
Supported by extensive studies exploring the mechanism of stem cells in the regulation of COPD, experts have demonstrated that stem cells possess multidirectional differentiation potential and are able to differentiate into specific forms of alveolar epithelial cells (type I and/or type II) and participate into the repair of lung tissue structure.
In this review, Chen et al. summarize the most relevant findings of eight clinical trials that explore the treatment of COPD with mesenchymal stem cells (MSCs).
These clinical trials, conducted between the years of 2009 – 2020, examined using different modes and doses of a variety of autologous or allogeneic MSCs, including bone marrow-derived stem cells (BM-MSCs), adipose tissue-derived stem cells (AD-MSCs), and umbilical cord-derived stem cells (UC-MSCs), in the treatment of COPD.
Examining the different types of MSCs used for these clinical trials, the authors conclude that while all types of MSCs have benefits in this application, AD-MSCs and UC-MSCs are very promising, primarily because the source is easily available; additionally, the process of collecting UC-MSCs is non-invasive. Looking at trends in recent clinical trials, the authors find a general increase in the shift toward using AD-MSCS and UC-MSCs and away from BM-MSCs, primarily for the reasons mentioned previously.
Analyzing results of these clinical trials related to mode, schedule, and dosage of administration, the authors found that stem cells administered intravenously into the body concentrated in the lungs for thirty minutes before gradually migrating to the liver; the inability of stem cells to keep stem cells in the lungs for a longer period of time was noted as a potential barrier that could limit the effectiveness of stem cell therapy for this condition.
To address this concern, the authors recommend adjusting the schedule and/or mode of administration, indicating that prior research suggests multiple doses and administration via airway injection using a bronchoscope is a good way to deliver stem cells directly to the lungs.
Chen et al. found that regardless of what type of MSCs and what mode of administration was used, stem cell therapy for the management of COPD has been proven to be safe and without evidence of any adverse events. However, only 2 of the eight clinical trials evaluated for this review demonstrated that MSCs could improve pulmonary function. The results of the other six indicated that MSCs had no effect on pulmonary function.
Considering these findings, and in view of the small number of patients in the two clinical trials demonstrating therapeutic improvement on pulmonary function, the authors call for further research to better understand the effects of MSCs on improvements of pulmonary function.
In closing, Chen et al. indicate that stem cell therapy may have a significant role in the future treatment of COPD and other respiratory diseases and offer a number of suggestions for future clinical trials. The recommendations provided by the authors for future clinical trials examining the therapeutic effects of MSCs when treating COPD include expanding the sample size, extending the follow-up time to a minimum of 2 years, selecting patients with different grades of COPD, considering using AD-MSCs and UC-MSCs (rather than BM-MSCs); and further exploring the effects of MSC on change in other inflammatory, immune, and metabolic indicators.
Source: “Stem cell therapy for chronic obstructive pulmonary disease – PMC.” 15 Jun. 2021, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280064/.
by admin | Jun 7, 2023 | Stem Cell Therapy, Mesenchymal Stem Cells, Osteoarthritis, Regenerative Medicine
Osteoarthritis (OA) is the most common form of arthritis and is estimated to affect over 500 million people worldwide. A result of the progressive deterioration of the protective cartilage that cushions the ends of the bones, OA most commonly affects the hands, knees, hips, and spine and is characterized by pain, stiffness, and loss of mobility in and around the affected areas.
Without a known way to treat and/or prevent OA from occurring, current conventional treatment of the condition typically involves a combination of prescription and OTC drugs, physical therapy, and lifestyle adjustments in an effort to treat and slow the progression of the symptoms associated with OA.
As the beneficial applications of stem cells continue to emerge, and considering their ability to replace and repair cells and tissues throughout the body, researchers believe that they can be used to treat joint disorders, including OA. The majority of the current stem cell therapies being investigated for use in treating OA use mesenchymal stem cells (MSCs), primarily due to their multilineage differentiation towards cell types in the joints and for their immunoregulatory functions.
In this review, Kong et al. provide detailed information on OA and MSCs, share updated information on pre-clinical and clinical trials and related applications of MSCs, and discuss additional efforts on cell-based therapy for treating OA and other joint and bone diseases.
Several preclinical models have investigated MSCs in treating OA and have demonstrated success in generating cartilage from MSCs. In addition, several animal models have demonstrated the beneficial effect of MSCs on cartilage, including protecting existing cartilage, repairing defects of joint cartilage, regenerating and enhancing cartilage, and even preventing OA.
Additionally, there have been several animal models evaluating the effects of intra-articular injection of MSCs for treating OA with researchers noting marked regeneration of tissue and decreased degeneration of articular cartilage.
Clinical trials using MSCs to treat human joint cartilage defects have found that MSCs could be used to repair cartilage defects, improve joint function, reduce pain, and have demonstrated the potential to use MSC therapy for cartilage repair and regeneration as a way to reduce signs and symptom commonly associated with OA.
Although these studies have demonstrated the tremendous potential associated with the use of MSCs for treating OA, they have also highlighted some potential concerns associated with MSC-based therapy. These concerns include determining the specific number and type of MSCs best suited for treating OA, a better understanding of the timing and delivery strategies for the administration of MSCs, and identifying the stages of disease best suited for MSC therapy.
Further concerns highlighted by the authors include the potential of genetic influences when using autologous MSC cells for treatment, the potential for the overall quality of MSC cells used in older patients to be too low, and the overall safety of stem cell therapy as a therapeutic treatment option for OA.
Despite the concerns identified above, Kong et al. conclude that the advancement of regenerative medicine and innovative stem cell technology offers a unique and exciting opportunity to treat OA.
Source: “Role of mesenchymal stem cells in osteoarthritis treatment – NCBI.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5822967/.
by admin | May 31, 2023 | Stem Cell Therapy, Regenerative Medicine
Neuropathic pain (NP) is a complex, wide-ranging, and often debilitating condition that contributes to chronic pain. Caused by a number of different factors and contributors, the condition most commonly involves disease, chronic condition, or injury to the nervous system.
Defined by the International Association for the Study of Pain (IASP) as pain that occurs as a direct consequence of a lesion or disease affecting the somatosensory system, NP is responsible for 20 to 25% of patients who experience chronic pain and is estimated to affect 8% of the population.
While there have been significant improvements in pharmacological and nonpharmacological treatment for NP, these practices only provide consistent and lasting pain relief to a small percentage of patients. Recently regenerative medicine, also known as stem cell therapy, is being explored as a safe and effective NP therapy option.
In this review, Joshi et al. explore the possibilities of using stem cells in NP patients and discuss the relevant challenges associated with their uses in this application.
After identifying and defining the nine most common conditions associated with chronic, persistent, or recurring NP, the authors begin this review by pointing out that NP, to date, has been poorly recognized, poorly diagnosed, and poorly treated. A review of relevant literature has also demonstrated that the treatment of NP has consistently been a significant challenge for physicians, with most attempting to manage NP by targeting clinical symptoms rather than causative factors.
Most often, pharmacological treatment approaches for managing NP have included a variety of first-line drugs (tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, and gabapentinoids) and opioid analgesics (tramadol) as second-line drugs. Third-line pharmacological NP treatment includes stronger opioids, such as morphine and oxycodone. Nonpharmacological NP treatment options for drug-refractory NP include interventional therapies (peripheral nerve blockade and epidural steroid injection), physical therapies (massage and ultrasound), and psychological therapies (cognitive behavioral therapy).
Long believed to arise from neurons, recent studies have demonstrated the important role of immune system response in the development of NP. Specifically, immune cells were found not only to be the source of pain mediators but also to produce analgesic molecules. These findings led researchers to believe that neutrophils and macrophages could each have a major role in early NP development.
Research has indicated that nerve injuries trigger an organized series of events to mount an inflammatory response. As part of this response to injury, pain following nerve damage has been shown to be mitigated by cytotoxic natural killer cells that selectively clear out partially damaged nerves. Additionally, this research has increasingly demonstrated that the immune system interacts with the sensory nervous system, contributing to persistent pain states.
Pharmacological and nonpharmacological treatment approaches have only produced temporary pain relief in patients with NP. Recently, stem cell transplantation has demonstrated significant potential for repairing nerve damage in NP and has emerged as a potential alternative therapeutic treatment approach. While the exact mechanism underlying stem cell-mediated pain relief remains unclear, specific stem cells (human mesenchymal stem cells, or hMSCs) have demonstrated the potential to provide trophic factors to the injured nerve as well as the ability to replace injured or lost neural cells.
While stem cell-based therapies have been shown to protect against neurodegeneration and promote neuroregeneration, the authors point out several issues that need to be addressed. These outstanding issues include identifying the optimal dosing for stem cell transplantation in the treatment of NP, sourcing of stem cells, considerations of autologous versus allogeneic transplants, precommitment to neuronal lineage, and specific dosing requirements.
Joshi et al. conclude that while NP is a chronic heterogeneous condition of the sensory nervous system with no current curative treatment, stem cells present exciting therapeutic prospects for NP. While further research to understand the exact mechanism underlying stem cell-mediated pain relief is required, current literature provides evidence of the potential of stem cells in slowing the degeneration process while promoting the survival and recovery of damaged nerves.
Source: Stem Cell Therapy for Modulating Neuroinflammation in … – NCBI.” 3 May. 2021, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124149/.
by admin | May 24, 2023 | Stem Cell Therapy, Mesenchymal Stem Cells, Stem Cell Research, Stroke
With nearly 15 million people affected worldwide each year, stroke continues to be the most prevalent cerebrovascular disease. Responsible for over 5 million deaths and another 5 million individuals suffering long-term disabilities, stroke also is the leading cause of mortality and morbidity worldwide.
Although there have been significant advances in both pharmacological and surgical therapies designed to treat the effects of stroke, effective therapy remains limited and primarily focused on managing the symptoms associated with a stroke rather than treating the causing factors or preventing the stroke at the onset.
Recently regenerative medicine, also known as stem cell therapy, and specifically mesenchymal stem cell (MSC)-based therapy has been identified as a potentially effective strategy for a wide range of diseases and health conditions, including stroke.
In this review, Li et al. examine current preclinical and clinical data from trials using MSCs in the treatment of stroke, the mechanisms underlying MSC-based therapy for stroke, and the challenges associated with the timing and delivery of MSCs.
Initial preclinical studies of the application of MSCs in the treatment of stroke demonstrated that transplantation of MSCs following ischemic stroke promoted improvement of cerebral function protected the ischemic neurons, and repaired brain damage. However, these studies were conducted in young and healthy subjects and failed to factor in the presence of comorbidities, such as diabetes and hypertension, more commonly observed in ischemic stroke patients.
Considering that 75% of strokes occur in the elderly and/or those with the previously mentioned comorbidities, the authors of this review focused their review on studies that incorporated these two factors into their trials.
While these preclinical studies of MSC-based therapy for stroke demonstrated promising results, including improved blood-brain barrier integrity, increased white matter remodeling, and improved neural repair, the authors point out that there has been a limited number of preclinical studies conducted and call for additional preclinical studies specifically utilizing the comorbidity model.
Although treatment of stroke using MSCs has been established to be safe and feasible in phase I and II clinical trials, there have been mixed findings as to the therapy’s efficacy. As a result of these varied findings, the overall efficacy in the treatment of ischemic stroke remains controversial. The authors consider several reasons for the inconsistency of results observed in these trials, including the varied number of patients, doses, and type of cell delivery, the timing of the cell therapy, and the treatment modalities used in these trials; the authors also call attention to the different locations, extent, and severity of lesions used in these trials.
As a result of the inconclusive results surrounding the effectiveness of MSC-based therapy for the treatment of stroke in these clinical trials, the authors call for more optimized and well-designed large-sample multicenter studies to evaluate the therapeutic efficacy of MSCs more thoroughly in ischemic stroke.
While the underlying mechanisms of MSC-based therapy for stroke have not been fully explained or understood, a review of several studies has demonstrated that MSCs protect against stroke through multiple mechanisms, including direct differentiation, paracrine effects, and mitochondrial transfer.
Before MSCs can be widely applied in clinical practice, Li et al. highlight several challenges that need to first be considered. These challenges include determining the optimal time for MSC administration during the acute stroke stages, further understanding the best treatment, conditions, and strategies to maximize the regenerative potential of MSCs, identifying the simplest and safest route of MSC delivery, and identifying the best source of MSCs for stroke treatment.
The authors conclude this review by recommending future preclinical and clinical studies that consider the adoption of a well-designed randomized controlled study design and method rigor and intervention measures to determine the effect of MSC therapy in the treatment of stroke.
Even with considering the above recommendations, MSCs continue to demonstrate exciting potential as a means to protect neurons and improve outcomes and overall quality of life for stroke patients.
Source: “Mesenchymal Stem Cell-Based Therapy for Stroke – NCBI.” 9 Feb. 2021, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899984/.
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