Mesenchymal stem cells (MSCs) are multipotent fibroblast-like cells found throughout the body and have been found to have self-renewing and multilinear therapeutic potential by providing new cells for tissue repair by replacing damaged cells.
Thought to stimulate repair and control the immune response through an expression of growth factors and other cytokines, MSCs are at low risk of rejection and repair tissue damage through immunomodulation, not by their ability to differentiate.
While MSCs can be isolated from a number of tissue sources, including bone marrow, peripheral blood, adipose (fat) tissue, umbilical cord blood, and umbilical cord tissue (Wharton’s jelly). MSCs derived from the human umbilical cords (UCMSCs) have been found to have significant advantages over MSCs isolated from other sources. These advantages include higher proliferation and self-renewal capacity and multilineage differentiation capability.
Unlike many sources of MSCs, the umbilical cord is considered medical waste, making the collection of UCMSCs noninvasive and eliminating ethical concerns associated with the collection of MSCs from other sources. These UCMSCs have been developed as effective “off-the-shelf” cell therapy for a number of conditions, including autoimmune diseases, and as a treatment for a number of emergency medical conditions.
This Phase 1 clinical study, designed and conducted by Chin et al., intended to determine the safety and efficacy of intravenous allogeneic infusion of UCMSCs in healthy volunteers and to determine the effective dose at which an immunomodulatory effect is observed. The findings of this study are intended to serve as a guideline and benchmark for future CVL-100 clinical research.
Analyzing the results of this clinical study, the authors report that there was no observed complication resulting from the infusion and no significant adverse event in either dosage group in the 6 months of follow-up. These findings led Chin et al. to conclude that UCMSCs infusion was safe among healthy subjects, results that were consistent with other UCMSC treatment-based studies.
The authors also reported that UCMSCs infusion posed no significant adverse effects in patients with type 2 diabetes. Despite the relatively small sample group of this study (11 subjects), the authors reported demonstrating an initial transient proinflammatory effect followed by a significant and prolonged anti-inflammatory effect.
In addition, Chin et al. report found that high-dose (HD) CLV-1000 infusion provided a significant increase in both hemoglobin level and MCV level that falls within the normal range. Biomarker assessment results also indicated that the HD group demonstrated a significant steady increase of cytokine IL-1RA from baseline up until 6 months of posttreatment. This finding is especially important as IL-1RA is a naturally occurring antagonist to the proinflammatory cytokine 1L-1.
The authors conclude that this study clearly demonstrates a difference in immunomodulatory effect between the high-dose and low-dose treatment groups, with the HD group demonstrating a significantly greater reduction of proinflammatory cytokine TNF-α and an increased level of specific anti-inflammatory cytokines within 6 months and in relation to those in the low dose group. Considering this, Chin et al. conclude that a CLV-100 dosage of two million MSCs per kilogram of body weight represents the optimal dose level for overcoming inflammatory conditions by displaying the best improvement in all parameters tested, absence of side effects, and SAEs.
The data collected in this study also suggests that this is the first study to report a significant reduction of globulin observed over the course of the study. This is important because globulin serves an important role in immunity. Additionally, increases in serum globulins are associated with several immune-mediated diseases, including rheumatoid arthritis, chronic liver disease, diabetes mellitus, and cancer.
Considering these findings, the authors of this study conclude that high doses of allogeneic MSCs could help exert beneficial effects of repair and healing.
Currently, it’s estimated that nearly 1.5 million Americans are living with type 1 diabetes (T1D), a number that is expected to increase to over 2 million by the year 2040. In the U.S. alone, healthcare costs and lost wages directly related to T1D currently exceed $16 billion per year.
While the most common treatment for T1D continues to be regular injections of insulin and is effective in improving hyperglycemia, the treatment has proven ineffective in removing autoimmunity and regenerating lost islets. Additionally, islet transplantation, a recent and experimental treatment option for T1D, has demonstrated its own set of issues, primarily poor immunosuppression and a limited supply of human islets.
The rapid progression and recent advances in stem cell therapy, including mesenchymal stem cell (MSC) therapy, have created interest in using stem cells to help manage the symptoms of T1D. In this review, Hai Wu reviewed the properties of MSCs and highlighted the progress of using MSCs in the potential treatment of T1D.
Diabetes clinics have demonstrated progress using depleting antibodies as a way to treat T1D, but continue to find remission to typically last for only a short period of time. Additionally, treatment with these antibodies has shown not to discriminate between different types of T cells, meaning even T cells involved in maintaining normal immune function are depleted; this phenomenon has been shown to contribute to other serious health complications.
In addition to the immunomodulatory effects demonstrated by MSCs, they have also shown the ability to recruit and increase the immunosuppressive cells of host immunity. Recent results from clinical trials have shown that just a single treatment with MSCs provided a lasting reversal of autoimmunity and improved glycemic control in subjects with T1D.
While these results demonstrate the potential of MSCs for a wide range of autoimmune diseases, Wu points out that the small sample size of these studies necessitates further clinical trials before considering approval for use in clinical applications.
Studies of human islets and human islet transplantation have been limited because of a shortage of pancreas donors. Although unable to be definitively demonstrated, and considering their ability to differentiate into other cell types, there is a hypothesis that MSCs can transdifferentiate to insulin-producing cells. While not yet fully understood, this hypothesis is further supported by the observation of crosstalk between MSCs and the pancreas in diabetic animals.
Other in vivo studies examining this relationship has produced mixed results. For example, Chen et al. (2004) were unsuccessful in attempts to transdifferentiate MSCs into insulin-producing cells in vitro. On the other hand, several studies, including those by Timper et al. (2006) and Chao et al. (2008) demonstrate the formation of islet-like clusters from in vitro cultured MSCs and the possibility of using MSCs as a source of human islets in vitro.
Despite these promising findings, the author highlights that most of these studies failed to generate sufficient amounts of islets required for human transplantation and long-term stability. However, Wu notes recent advances in tissue engineering, including biocompatible scaffolds, might better support in vitro generation of islets from MSCs.
The author concludes that MSCs can be isolated from multiple tissues, are easily expanded and genetically modified in vitro, and are well-tolerated in both animal and human studies – making them a good candidate for future cell therapy. On the other hand, stem cell therapy alone might not be enough to reverse the autoimmunity of T1D, and co-administration of immunosuppressive drugs may be necessary to prevent autoimmunity.
MSCs have shown great promise in the field of regenerative medicine. While stem cells used as a potential treatment for T1D appear generally safe, the author calls for future in-depth mechanistic studies to overcome the identified scientific and manufacturing hurdles and to better learn how cell therapy can be used to treat – and eventually cure – T1D.
According to recent data from the CDC, an estimated 30 million Americans currently have type 2 diabetes mellitus (T2DM), and another 88 million are considered to be prediabetic.
Occurring most often as a result of being overweight and/or sedimentary and often resulting in severe kidney, heart, or vision issues, T2DM has demonstrated to be difficult to treat, often resulting in life-long insulin therapy as the primary method of treatment.
Considering the negative impacts associated with insulin treatment, and T2DM in general, Liu, et al.’s research explores the potential of specific mesenchymal stem cells (MSCs) in the treatment of the condition.
Recently, stem cell therapy has been shown to be beneficial in improving glycemic control and beta function. Building off of these findings, Liu, et. al designed this study to specifically examine the efficacy and safety of Wharton’s Jelly mesenchymal stem cells transplantation (WJ-MSC) as a therapeutic option for those with T2DM.
The authors’ single-center phase I/II study involved observing 22 patients with T2DM for 12 months after receiving two injections of WJ-MSC (one intravenously and one intrapancreatic endovascularly). Over the course of the 12-month observation period, the participants were monitored with primary endpoints observed including changes in the levels of glycated hemoglobin and C-peptide and secondary endpoints including insulin dosage, fasting blood glucose, post-meal blood glucose, inflammatory markers, and T lymphocyte counts.
At the conclusion of this study, Liu et al. found that both glycated hemoglobin and fasting glucose levels demonstrated a progressive decline after WJ-MSC transplantation and over the course of the 12-month follow-up period, the suggested potential of long-lasting effects of the WJ-MSC treatment. Researchers also observed a general improvement in fasting C-peptide levels. Secondary endpoint observations over the course of the 12-month follow-up included improved beta-cell function and reduced markers of systemic inflammation and T lymphocyte counts.
While there were no significant adverse observed effects associated with either of the WJ-MSC injections, the authors did note isolated and separate incidences of mild fever, nausea, and headache in a very small number of participants – all of which spontaneously resolved within a week of onset. The authors also noted a temporary decrease in levels of C-peptide and beta-cell function one month after treatment, possibly related to the intrapancreatic endovascular injection. As a result of these observations, the authors call for further investigation of the safety of intrapancreatic endovascular delivery of WJ-MSC.
As a result of this research, Liu et al. concluded that their findings suggest the possible therapeutic potential of WJ-MSC transplantation for treatment of T2DM and specifically with improved beta-cell function, systemic inflammation, and immunological regulation. The authors also call for further large-scale placebo-controlled clinical studies to fully understand the safety and efficacy of WJ-MSCs in the treatment of T2DM. Source: “PMC – NCBI.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4055092/
The Mediterranean diet emphasizes nutrient-rich eating from sources such as vegetables, healthy fats, whole grains, fruits, and lean protein. The dietary approach has been praised for its health benefits in recent years, including improved heart health. Now, it’s also been hailed as a beneficial diet for people with type 2 diabetes, thanks to its ability to improve several key biomarkers, such as inflammation, insulin resistance, body mass index (BMI), and HDL cholesterol.
How the Mediterranean Diet Helps with Type 2 Diabetes
The Mediterranean diet is a flavorful eating pattern based on the dietary habits of people in countries near the Mediterranean Sea. It offers filling meal options that prioritize the nutrients bodies need to perform their best, while also limiting additives such as refined carbohydrates, red meat, and added sugars.
According to research published by the American Journal of Clinical Nutrition, participants of the Mediterranean diet had the best A1C scores, which measure blood sugar over a three-month period. They also lost more weight and had the best cardiovascular health, including improved cholesterol levels, compared to peers who participated in high-protein, high-fiber, vegetarian, vegan, or low-carbohydrate diets.
While this heart-healthy diet can’t reverse diabetes, it can help reduce the risk of complications related to the disease. By reducing cholesterol, it protects the heart, thereby limiting the risk for serious issues such as heart attack and stroke. The diet also has anti-inflammatory and antioxidant properties, which can reduce the risk of cardiovascular events by as much as 30%.
Which Foods Can You Eat on the Mediterranean Diet?
Fortunately, the Mediterranean diet isn’t restrictive and is quite simple. The idea is to incorporate as many fresh fruits and vegetables into your diet as possible and prioritize lean meat or plant-based protein, such as skinless chicken, fish, and legumes. Here are a few examples of which foods are commonly eaten in the diet:
Whole Grains: Choose whole-grain bread and pasta products, as well as quinoa, brown rice, barley, and farro.
Nuts, Seeds, & Beans: Heart-healthy nuts like almonds, walnuts, cashews, and pistachios are excellent choices. You can also have sunflower and sesame seeds, beans such as kidney, white, black, and cannellini beans, chickpeas, and lentils.
Vegetables: Eat a variety of vegetables such as bell peppers, Brussels sprouts, asparagus, leafy greens, broccoli, cabbage, artichokes, carrots, beets, fennel, onions, and zucchinis, among others.
Fruits: While fruits do naturally contain sugars, they are also nutrient-rich and can be enjoyed in moderation. Consider snacking on melons, figs, dates, grapes, citrus fruits, berries, and apples.
Healthy Fats: Olive oil is a great source of healthy fats, and can be used for cooking or salads.
Fresh Fish & Seafood: Salmon, shrimp, halibut, mackerel, herring, trout, and other seafood rich in healthy fats are among the best protein sources.
Dairy & Poultry: Reduced-fat cheese, low-fat yogurt and milk, eggs, and lean poultry are all welcome choices on the Mediterranean diet.
While switching to an entirely new eating style can be overwhelming, you might consider taking small steps to work towards a full Mediterranean dietary lifestyle. For instance, you might start by reducing or eliminating processed foods, then aim to incorporate vegetables with most of your meals. Making healthy dietary choices can deliver numerous wellness benefits and is a worthwhile endeavor, even if it takes some time to adapt.
For people with diabetes or pre-diabetes, making healthy
dietary choices is an important aspect of disease management. In particular,
patients should avoid foods that are known to spike blood sugar to keep their
levels within a healthy range. Even for individuals who aren’t diabetic,
limiting or avoiding these foods can help to prevent against serious health
issues, including insulin resistance, obesity, and heart disease. Discover some
of the worst culprits behind elevated blood sugar below.
White Grain Products
While limiting your consumption of grain products may have
certain health benefits, you don’t have to skip rice and bread products altogether.
Simply steer clear of white rice and bread, and opt for whole-grain varieties
instead. In particular, eating white
rice regularly has been associated with an increased risk of type 2
diabetes. This could be a result of the food’s lack of fiber, which helps to
regulate blood sugar levels. White bread, too, is linked to a higher risk of
type 2 diabetes and heart disease.
It’s made from refined flour, which is digested too quickly and can therefore
spike blood sugar.
Too much red meat increases the likelihood of developing
diabetes, especially when it’s processed. Even just two slices of bacon or one
hot dog eaten daily can increase a person’s risk of type 2 diabetes by as much
Red meat has also been linked to higher levels of colorectal cancer and cardiovascular
disease. Researchers suspect that while the saturated fat found in red meat is
one part of the problem, the high level of sodium, which can increase blood
pressure and create insulin resistance, is also to blame.
Fried, greasy foods may look appetizing, but they’re among
the worst offenders on this list. Most varieties have soaring calorie, fat, and
salt counts, all of which spike blood sugar. Salty fast food is particularly
dangerous, as it can increase blood pressure. Because diabetes patients already
face a higher risk of heart
disease, controlling blood pressure is critically important to their health.
Commercially prepared baked goods and other packaged snacks
should be avoided, or at least eaten in moderation. Many of these options have
harmful additives and are high in trans fats, which can impact your cholesterol
and lead to inflammation. Snacking on whole foods, such as a handful of
almonds, vegetable sticks, roasted chick peas, and hard-boiled eggs will
deliver more nutritious benefits in between meals.
As mentioned above, saturated fat can lead to insulin
resistance, or the body’s inability to use insulin for energy. When this
happens, insulin builds up in the blood, leading to higher blood sugar levels.
While not all dairy contributes to this issue, whole milk and other full-fat
dairy products are particularly high in saturated fats. For this reason,
diabetics should choose reduced or nonfat dairy products, including yogurts and
cheeses, whenever possible.
Making necessary diet changes to keep the blood sugar levels under control is key especially for those with diabetes. Focus on consuming foods that improve your condition and keep your diabetes under control. There are some key foods identified by researchers that are known to improve the condition and reduce the risk:
The tiny berries are a source of daily good carbs and research also shows that eating blueberries improves sensitivity to insulin. The phytochemicals present in blueberries also have special anti-inflammatory properties that are known to reduce the risk of cardiovascular diseases especially the ones associated with diabetes type 2.
Incorporate more clementines, grapefruits, and oranges in your daily diet. Research shows that consuming citrus fruits can have a long-term positive effect on blood sugar and cholesterol levels. Research conducted at Harvard University showed that consuming the whole fruit with the pulp rather than just the juice reduces the risks of diabetes type 2. This is due to the presence of their soluble fiber and the compound called hesperidin which is an anti-inflammatory by nature.
Is it possible that a sweet treat like chocolate can control glucose levels? Yes, studies show that high-quality dark chocolate if consumed daily can decrease blood pressure and fasting insulin levels. This is achieved due to the presence of the compound called polyphenols. Try replacing unhealthy carbs with a high-quality low sugar dark chocolate to improve the glucose levels while also satisfying your taste buds.
Chickpeas are quite well-known for having a low glycemic index, making it very beneficial for diabetes. New research also suggests that consuming legumes has a very therapeutic effect on the body. Compared to others, people who consume a cup of legumes daily showed a significant decrease in blood pressure and hemoglobin values.
Replacing unhealthy fats with good healthy fats is suggested for everybody but especially for those who have diabetes type 2. Consumption of extra virgin olive oil has been proven to be associated with the decreased risk of diabetes and improves glucose levels because of its anti-inflammatory properties. Try to incorporate olive oil as much as possible in your diet like including it as a dressing for your salads.
It is observed that vegetarians have a lower risk of diabetes 2 development. A study published in 2012 showed that a diet that is mainly centered around fresh fruits, nuts, vegetables, and legumes has a major positive effect on people who are diabetic. Some participants who strictly followed this diet showed a significant decrease in hemoglobin type A1, blood pressure, HDL levels, and triglycerides. Almost 60% of the participants resulted with glucose levels within the normal range.
Diabetes patients who had a high intake of non-starchy leafy green vegetables showed a significant decrease in the levels of hemoglobin and risk of cardiovascular diseases. Advanced research is being carried out to see whether these effects were specifically due to the presence of vitamins A, C, and E in the dense green leafy vegetables. It is also observed that best results were obtained when people consumed a minimum of 200 grams of vegetables daily. This included around 70g of green vegetables.
Nuts and Peanut Butter
Having 5 servings of nuts a week showed a major reduction in the stroke risk and heart disease in women with diabetes type 2. A study published also showed that diabetic patients consuming 2 ounces of nuts daily as a substitute to regular carbohydrates had improved blood sugar levels and blood lipids. Try incorporating daily carbs like almonds, walnuts and peanut butter instead of unhealthy carbs. Be sure to watch the sodium intake and portion size.
Many studies have shown that including good bacteria in your diet has a positive effect on glucose regulation. Consuming food such as probiotic yogurt significantly improves the HgbA1 and glucose levels when consumed for eight weeks or longer.
Cinnamon increases the sensitivity to insulin which in turn reduces blood sugar. The science behind how this spice does the job is still under study however, a majority of the studies conducted thus far have shown cinnamon as an aid to controlling the glucose level of blood if consumed regularly and long term. You can incorporate cinnamon in your diet by sprinkling it on foods you regularly eat like nuts, oatmeal, butter and yogurt.
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