Stem-ulating research

Two branches of stem cell research discover the impact on both diabetes and cardiac damage

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Stem cells are enjoying a renaissance lately, and preclinical research is applying them to everything in sight—from Alzheimer’s disease, eye diseases and cancer to orthopedics, Parkinson’s disease and stroke therapy.
One new study elucidates how adipose-derived stem cells can improve metabolic balance. Meanwhile, at the Icahn School of Medicine at Mount Sinai, researchers have recently discovered that placental stem cells from mice can target heart injuries, and start to repair damage.
An article in Experimental Biology and Medicine suggests a new therapeutic strategy for type 2 diabetes and obesity. The study led by Dr. Bing Wang, a professor in the department of general surgery at Shanghai Ninth People’s Hospital and Shanghai Jiao Tong University School of Medicine in China, reports that transplantation of adipose tissue-derived mesenchymal stem cells (ADSCs) improves metabolic balance and reduces inflammation in an animal model.
Sedentary lifestyles, along with high-fat and sugar diets, have increased the prevalence of diabetes. The World Health Organization estimates that 90 percent of the 347 million people worldwide with diabetes have type 2 diabetes (T2D). Obesity can be a contributing factor for T2D diabetes, and the inflammation that occurs in obesity exacerbates insulin resistance.
A preliminary clinical study showed that transplantation of mesenchymal stem cells improves metabolic balance in patients with T2D. ADSCs are abundant and can be harvested with minimally invasive procedures, but their ability to improve metabolic function in T2D or obesity was not known.
In the new study, Wang and colleagues assessed the ability of ADSCs to alleviate insulin resistance in high-fat diet (HFD)-fed mice. HFD-fed mice receiving ADSCs exhibited reduced blood glucose levels and enhanced insulin sensitivity. ADSCs overexpressing neuregulin 4, a growth factor with beneficial effects in obesity and T2D, were the most effective in reducing blood glucose and insulin resistance.
“Our study shows that neuregulin overexpression could improve the efficacy of ADSCs in ameliorating insulin resistance and other obesity-related metabolic disorders and may provide a new therapeutic strategy for the treatment of obesity, insulin resistance and T2D,” said Wang, senior author of the study.
These protective effects were due to the suppression of inflammation and augmentation of glucose uptake in skeletal muscle and adipose tissues. Collectively, these studies demonstrate that ADSC transplantation improves glucose tolerance and metabolic balance in HFD-fed mice by multiple mechanisms.
Dr. Steven R. Goodman, editor-in-chief of Experimental Biology & Medicine, pointed out that “Wang and colleagues have provided a potential new therapeutic option for type 2 diabetics who are obese. If future clinical trials using this approach are efficacious, this will provide a valuable new treatment for Type 2 diabetics.”
And not long ago in May, researchers at the Icahn School of Medicine at Mount Sinai discovered that stem cells derived from the placenta known as Cdx2 cells can regenerate healthy heart cells after heart attacks in animal models. Cdx2 cells can migrate through the circulatory system and target heart injuries. Once there, the cells transform into beating heart cells and start the repair process.
The findings, published in Proceedings of the National Academy of Sciences (PNAS), could represent a novel treatment for cardiac regeneration. Researchers were able to isolate Cdx2 cells from full-term human placentas too, raising the possibility of being able to harvest the treatment from placentas that would normally be discarded, noted principal investigator Dr. Hina Chaudhry, director of Cardiovascular Regenerative Medicine at the Icahn School of Medicine at Mount Sinai.
“Cdx2 cells have historically been thought to only generate the placenta in early embryonic development, but never before were shown to have the ability to regenerate other organs, which is why this is so exciting. These findings may also pave the way to regenerative therapy of other organs besides the heart,” added Chaudhry. “They almost seem like a super-charged population of stem cells, in that they can target the site of an injury and travel directly to the injury through the circulatory system and are able to avoid rejection by the host immune system.”
The Mount Sinai research team had previously discovered that a mixed population of placental stem cells helped the hearts of pregnant female mice recover after an injury that could otherwise lead to heart failure. The current study aimed to determine what type of stem cells made the heart cells regenerate. The investigators looked at Cdx2 cells, and found them to comprise the highest percentage (40 percent) of those assisting the heart from the placenta.
To test the Cdx2 cells’ regenerative properties, the researchers induced heart attacks in three groups of male mice. Magnetic resonance imaging was used to analyze mice immediately after the heart attacks, and three months after induction with cells or saline. They found that every mouse in the group with Cdx2 stem cell treatments had significant improvement and regeneration of healthy heart tissue. Three months post-treatment, the stem cells had migrated directly to the heart injury and formed new blood vessels and cardiomyocytes.
Researchers found that Cdx2 cells have all the proteins of embryonic stem cells, and additional proteins which give them the ability to travel directly to the injury site—something embryonic stem cells cannot do. Cdx2 cells also appear to avoid the host immune response, and did not reject the cells when administered from the placenta to another animal.
“These properties are critical to the development of a human stem cell treatment strategy, which we have embarked on, as this could be a promising therapy in humans. We have been able to isolate Cdx2 cells from term human placentas also; therefore we are now hopeful that we can design a better human stem cell treatment for the heart,” explained Chaudhry. “Past strategies tested in humans were not based on stem cell types that were actually shown to form heart cells, and use of embryonic stem cells for this goal is associated with ethics and feasibility concerns. Placentas are routinely discarded around the world and thus almost a limitless source.”
“These results were very surprising to us, as no other cell type tested in clinical trials of human heart disease was ever shown to become beating heart cells in petri dishes, but these did and they knew exactly where to go when we injected them into the circulation,” stated first author Dr. Sangeetha Vadakke-Madathil, postdoctoral fellow in medicine (cardiology) at the Icahn School of Medicine at Mount Sinai.

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