Impaired cardioprotective function of transplantation of mesenchymal stem cells from patients with diabetes mellitus to rats with experimentally induced myocardial infarction

Abstract

BackgroundDiabetes mellitus (DM) exacerbates coronary artery disease (CAD) morbidity and mortality. Mesenchymal stem cells (MSCs) play an important therapeutic role in myocardial ischemic injury. However, little is known about changes in the cardioprotective characteristics of MSCs from patients with DM.MethodsSternal bone marrow aspirates were taken at the time of coronary artery bypass graft surgery. The morphology and growth characteristics of hMSCs were observed in passage 3. Differences in gene expression profiling were measured by Affymetrix GeneChipHuman Genome U133 Plus 2.0 Arrays. Forty two adult male rats with experimentally CAD were randomized into three groups. MSCs from patients with CAD+DM or CAD were injected into the infarcted myocardium. Control animals received culture medium. Echocardiography, TUNEL, immunohistochemistry and Western-blot analysis were performed 4 weeks after transplantation.ResultsGrowth curves showed that proliferation of hMSCs in the CAD+DM group was significantly lower than in the CAD group. Nine transcripts of genes related to apoptosis containing Bcl-2 were found to differentiate the two groups. Transplantation of hMSCs in the infarcted border zone improved cardiac function, but DM partly impaired this effect. Similar results were observed from TUNEL, immunohistochemistry and Western-blot analysis.ConclusionshMSCs from patients with CAD+DM and CAD alone both have proliferative properties. Transplantation of hMSCs ameliorate heart function, but proliferative ability and myocardial protection decrease significantly in MSCs obtained from patients with CAD+DM compared with cultures from patients with CAD alone, possibly as a result of differences in Bcl-2 protein expression and reduced anti-apoptosis.

Umbilical Cord Mesenchymal Stromal Cells Affected by Gestational Diabetes Mellitus Display Premature Aging and Mitochondrial Dysfunction

“…GDM-UC-MSCs did not commonly grow above passage 6 or 7, whereas one of the N-UC-MSC lines from normal term pregnancies grew until passage 37 in our culture conditions (unpublished data). These results are consistent with the report of Liu et al, which stated that MSCs isolated from the sternal bone marrow of a DM patient group exhibit lower growth than those isolated from a control group [38]. Gene expression profiling of DM MSCs revealed increased expression of genes related to tumor necrosis factor-related apoptosis pathways and decreased expression of antiapoptotic genes such as Bcl-2.…”

Effects of autologous adipose-derived stem cell infusion on type 2 diabetic rats

“…The higher level of heterogeneity of ASC suggests that those cells do represent MSC that have more lineage capabilities than BM-MSC [16,17]. However, the effects of diabetes on ASC leads to a gradual depletion of the ASC pool, as with BM-MSC [18,19]. More studies have confirmed that MSC therapy could effectively ameliorate both type 1 and type 2 diabetes [20][21][22], while there are few reports on the effects of ASC on the late phase of type 2 diabetes.…”

Advanced Age Impairs Cardioprotective Function of Mesenchymal Stem Cell Transplantation from Patients to Myocardially Infarcted Rats

“…MSCs were isolated and cultured as previously reported [18]. Briefly, at the time of coronary artery bypass graft surgery (CABG), bone marrow was aspirated from the sternum and then mixed immediately with heparin.…”