Umbilical Cord Stem Cells Normalize Blood Glucose Levels in Diabetic Mice

Diabetes mellitus results from an insufficiency of insulin (Type 1 diabetes) or an inability to properly respond to insulin (Type 2 diabetes). Type 1 diabetes is caused by an attack by the patient’s own immune system on their pancreatic beta cells, which synthesize and secrete insulin. It is a disease characterized by inflammation in the pancreas. This suggests that abatement of inflammation in the pancreas might provide relief and delay the onset of diabetes.

Mesenchymal stem cells isolated from umbilical cord connective tissue, which is also known as Wharton’s jelly (WJ-MSCs), have the ability to reverse inflammatory destruction and might provide a way to delay or even reverse the onset of Type 1 diabetes.

To test this possibility, Jianxia Hu, Yangang Wang, and their colleagues took 60 non-obese diabetic mice and divided them into four groups: a normal control group, a normal diabetic group, a WJ-MSCs prevention group that was treated with WJ-MSCs before the onset of diabetes, and a WJ-MSCs treatment group that was treated with WJ-MSCs after the onset of diabetes.

After their respective treatments, the onset time of diabetes, levels of fasting plasma glucose (FPG), fed blood glucose levels and C-peptide (an indication of the amount of insulin synthesized), regulation of cytokines, and islet cells were examined and evaluated.

After WJ-MSCs infusion, fasting and fed blood glucose levels in WJ-MSCs treatment group decreased to normal levels in 6-8 days and were maintained for 6 weeks. The levels of fasting C-peptide of the WJ-MSC-treated mice was higher compared to diabetic control mice. In the WJ-MSCs prevention group, WJ-MSCs protected mice from the onset of diabetes for 8-weeks, and the fasting C-peptide in this group was higher compared to the other two diabetic groups.

Other comparisons between the WJ-MSC-treated group and the diabetic control group, showed that levels of regulatory T-cells (that down-regulate autoinflammation), were high and levels of pro-inflammatory molecules such as IL-2, IFN-γ, and TNF-α. The degree of inflammation in the pancreas was also examined, and pancreatic inflammation was depressed, especially in the WJ-MSCs prevention group.

These experiments show that infusions of WJ-MSCs can down-regulate autoimmunity and facilitate the recovery of islet β-cells whether given before or after onset of Type 1 Diabetes Mellitus. THis suggests that WJ-MSCs might be an effective treatment for Type 1 Diabetes Mellitus.

See March 2014 edition of the journal Endocrine.

Umbilical Cord Stem Cells Preserve Heart Function After a Heart Attack in Mice

A consortium of Portuguese scientists have conducted an extensive examination of the effects of mesenchymal stromal cells from umbilical cord on the heart of mice that have suffered a massive heart attack. Even more remarkable is that these workers used a proprietary technique to harvest, process, and prepare the umbilical cord stem cells in the hopes that this technique would give rise to a commercial product that will be tested in human clinical trials,

Human umbilical cord tissue-derived Mesenchymal Stromal Cells (MSCs) were obtained by means of a proprietary technology that was developed by a biomedical company called ECBio. Their product,, UCX®, consists of clean, high-quality, umbilical cord stem cells that are collected under Good Manufacturing Practices. The use of Good Manufacturing Practice means that UCX is potentially a clinical-grade product. Thus, this paper represents a preclinical evaluation of UCX.

This experiments in this paper used standard methods to give mice heart attacks that were later received injections of UCX into their heart muscle. The same UCX cells were used in experiments with cultured cells to determine their effects under more controlled conditions.

The mice that received the UCX injections into their heart muscles after suffering from a large heart attack showed preservation of heart function. Also, measurements of the numbers of dead cells in the heart muscle of heart-sick mice that did and did not receive injections of umbilical cord cells into their hearts showed that the umbilical cord stem cells preserved heart muscle cells and prevented them from dying. Additionally, the implanted umbilical cord MSCs induced the growth and formation of many small blood vessels in the infarcted area of the heart. This prevented the heart from undergoing remodeling (enlargement), and preserved heart structure and function.

When subjected to a battery of tests on cultured cells, UCX activated cardiac stem cells, which are the resident stem cell population in the heart. Implanted UCX cells activated the proliferation of cardiac stem cells and their differentiation into heart muscle cells. There was no evidence that umbilical cord MSCs differentiated into heart muscle cells and engrafted into the heart. Rather UCX seems to help the heart by means of paracrine mechanisms, which simply means that they secrete healing molecules in the heart and help the heart heal itself.

In conclusion, Diana Santos Nascimento, the lead author of this work, and her colleagues state that, “the method of UCX® extraction and subsequent processing has been recently adapted to advanced therapy medicinal product (ATMP) standards, as defined by the guideline on the minimum quality data for certification of ATMP. Given that our work constitutes a proof-of-principle for the cardioprotective effects UCX® exert in the context of MI, a future clinical usage of this off-the-shelf cellular product can be envisaged.”

Preclinical trials with larger animals should come next, and after that, hopefully, the first human clinical trials will begin.

Human Umbilical Cord Mesenchymal Stem Cells and Rheumatoid Arthritis

A collaborative study between physicians at the Hospital of Chinese People’s Liberation Army and the University of Oklahoma Health Sciences Center has examined the efficacy of umbilical cord mesenchymal stem cell treatments in combination with drugs in patients with active rheumatoid arthritis (RA).

RA may exist in 0.5-1.0% of the general population. In 2005, an estimated 1.5 million US adults aged ≥ 18 (0.6%) had RA. RA is characterized by chronic inflammation of the joints that causes cartilage and bone damage and deformity. It occurs in women two to three times more often than men.

Treatment of RA requires the administration of disease-modifying antirheumatic drugs (DMARDs), Unfortunately, these drugs have sizable side effects, and less debilitating treatments would be a welcome addition to the treatment options for RA patients.

A paper by Liming Wang and colleagues that was published in Stem Cells and Development examines the efficacy of combining DMARDs with infusions of umbilical cord mesenchymal stem cells (MSCs). Since MSCs have the ability to suppress an overactive immune response, such treatments might provide relief from the symptoms of RA and decrease the dependence on DMARDs.

In this study, Wang and others enrolled 172 RA patients and divided them into two groups: 36 of them were treated with DMARDs alone and 136 were treated with DMARDs plus umbilical cord MSCs (UC-MSCs). Of these 136 patients, 76 were treated for 3 months, 45 for 6 months, and 15 for 8 months. Each of these groups consisted of patients who could and who could not tolerate DMARDs. All patients in the second group received 4 x 10[7] UC-MSCs in 40 milliliters of liquid, but the first group received stem cell “solvent” (whatever that is) without UC-MSCs.

The results clearly showed that UC-MSCs treatments are safe. Patients blood work-ups before and after treatment show no significant differences. Secondly, the DMARD-only group did not show any improvements, but they did not get worse either. The DMARD + UC-MSC group showed quantifiable improvements. These patients reported feeling better in health assessment questionnaires, their serum levels of C-reactive protein and rheumatoid factor went down and their numbers of regulatory T-cells went up. The joint evaluations of these patients also improved (the so-called DAS28 score). All of these are measures of the severity of RA, and in the DMARD + UC-MSC groups, all the these markers improved.

Other markers of RA severity such as IL-6 and TNF-alpha also decreased in the DMARD + UC-MSC patients.

From these data, Wang and others conclude that “UC-MSCs are suitable pllications in the clinic and provide an additional choice to many RA patients.”

The data in this paper are rather clear. The benefits of a single UC-MSC treatment are significant. For this reason, umbilical cord MSCs should be regarded as a potential adjuvant treatment for RA patients.