Mesenchymal Stem Cells from Diabetic Patients Show Impaired Abilities


When using a patient’s own stem cells to treat their diseases, there is a caveat to such a treatment. Things like great age, diabetes mellitus, or a heart attack can seriously compromise the quality of the patient’s stem cells.

To determine if a patient’s stem cells can potentially work under certain circumstances, it is necessary that we test them. With that in mind, Huishan Wang’s laboratory from Shenyang Northern Hospital in Liaoning, China, has extracted mesenchymal stem cells from the bone marrow of patients with type II diabetes. These bone marrow stem cells were used to treat rats that had suffered heart attacks. As a comparison, Wang and his associates used mesenchymal stem cells from the bone marrow of patients diagnosed with coronary artery disease, but not diabetes mellitus.

In these experiments, all patients were between the ages of 50 to 60 years of age, had type II diabetes for at least 10 years, previously suffered a heart attack, and had no signs of liver, kidney or infectious diseases, and no cancer. Bone marrow samples were taken from the breastbone (sternum) during coronary bypass surgery, and the mesenchymal stem cells (MSCs) were extracted from the bone marrow and grown in culture for up to three passages. Ten diabetic patients were selected and two non-diabetic patients were used as a control group.

Male rats (Sprague-Dawley rats for those who are interested) were given heart attacks and then the MSCs were injected into the heart tissue in the area of the heart scar and in the areas adjacent to the heart scar. One group of rats received injections of MSCs from the patients that had type II diabetes, the second group with MSCs from the non-diabetic patients, and a third group rats received only injections of culture medium. The rats were given shots on the drug cyclosporine to ensure that none of the mice rejected their grafted cells. Heart function was assessed with echocardiography, and the tissue was examined, post-mortem, with a “TUNEL” assay, to determine the number of dead cells in the heart, and protein expression was also determined with Western blots.

The MSCs were tested for growth characteristics in culture and gene expression patterns were assayed with microarray studies.

Wang and others found that the MSCs from diabetic patients grew noticeably slower in culture than MSCs from non-diabetic patients. Also, the gene expression profiles a few significant examples; levels of the anti-cell death protein Bcl-2 were significantly lower in MSCs from diabetics.

When it came to the heart function of rats that had received MSC injections after a heart attack, those rats that had received MSCs from diabetic patients fared far worse than those that had received the MSCs from non-diabetics. Also, hearts that had received MSCs from diabetic patients had great amounts of cell death, and expressed significantly lower amounts of growth factors, and the anti-cell death protein Bcl-2.

These data show that MSCs from diabetic patients are impaired in the proliferative ability, and in their survival. This poor survival is due to lower levels of the anti-cell death protein Bcl-2.

Bcl2 activity
Bcl2 activity

A consequence of these experiments is that autologous or self stem cell transplantations in type I diabetics will probably be unsuccessful. This means that allogeneic transplantations or transplants that use stem cells from donors who are not diabetics are a better strategy for treating diabetics.

Published by

mburatov

Professor of Biochemistry at Spring Arbor University (SAU) in Spring Arbor, MI. Have been at SAU since 1999. Author of The Stem Cell Epistles. Before that I was a postdoctoral research fellow at the University of Pennsylvania in Philadelphia, PA (1997-1999), and Sussex University, Falmer, UK (1994-1997). I studied Cell and Developmental Biology at UC Irvine (PhD 1994), and Microbiology at UC Davis (MA 1986, BS 1984).