Induced Pluripotent Stem (iPS) Cells Inhibit Apoptosis and Fibrosis in Streptozotocin-Induced Diabetic Rats

Huang

Evidence-Based Complementary and Alternative Medicine

et al. 2018

Aims. To study the effect of the Chinese herb Yi-qi-huo-xue on cardiomyopathy in diabetic rats. Methods. Rats were fed a high fat and high glucose diet and injected with 50 ml/kg streptozotocin (STZ) to induce diabetic cardiomyopathy (DCM), followed by treatment with Yi-qi-huo-xue for 4 weeks. We measured the rats' heart weight index, observed the myocardial morphology using hematoxylin eosin (HE) staining, and determined the content of collagen types I and III in the myocardium using enzyme-linked immunosorbent assay (ELISA). We determined Bcl-2, Bax, and P53 protein expression by Western blot analysis and the cardiomyocyte apoptosis rate via a flow cytometry assay. Results. Compared with the rats in the control group, the diabetic rats gained weight and had increased blood sugar levels, an enhanced heart weight index, and increased myocardial pathophysiological damage. There was a decrease in their Bcl-2 expression, and their Bax and P53 expression increased. The Bcl-2/Bax ratio was enhanced, and there was an increase in the content of collagen types I and III in the myocardium. After treatment with Yi-qi-huo-xue, all levels listed above returned to normal. Conclusion. The Chinese herb Yi-qi-huo-xue degraded the myocardial interstitial collagen types I and III to protect the myocardium of the diabetic rats, thus delaying the role of myocardial fibrosis. Yi-qi-huo-xue could play an important role in protecting the myocardium of DCM rats by enhancing the expression of the Bcl-2 protein, inhibiting the expression of the Bax and P53 proteins, increasing the ratio of Bcl-2/Bax, and inhibiting the apoptosis of cardiomyocytes.

Section: Discussionsupporting

confidence: 66%

The Chinese Herb Yi‐Qi‐Huo‐Xue Protects Cardiomyocyte Function in Diabetic Cardiomyopathy

Huang

Evidence-Based Complementary and Alternative Medicine

et al. 2018

The Journal of Pathology

“…Recently, iPSCs have been generated from cardiac ventricular specific cell types instead of the commonly used mouse and human fibroblasts. These cells were effective in reducing fibrosis and the infarct zone following MI [47], and in diabetes-induced cardiomyopathy [48], probably through autocrine or paracrine mechanisms that remain to be determined. More recently, it has been reported that transcription factors such as GATA4, HAND2, MEF2C, and TBX5 (GHMT) can reprogram cardiac fibroblasts into functional cardiac-like myocytes in vitro and in vivo.…”

Section: Induced Pluripotent Stem Cells (Ipscs)mentioning

confidence: 97%

Stem cell transplantation as a therapy for cardiac fibrosis

Elnakish

Kuppusamy

Khan

2012

Cardiac fibrosis is a fundamental constituent of most cardiac pathologies and represents the upshot of nearly all types of cardiac injury. Generally, fibrosis is a scarring process, characterized by accumulation of fibroblasts and deposition of increasing amounts of extracellular matrix (ECM) proteins in the myocardium. Therapeutic approaches that control fibroblast activity and evade maladaptive processes could represent a potential strategy to attenuate progression towards heart failure. Currently, cell therapy is actively perceived as an alternative to traditional pharmacological management of myocardial infarction (MI). The majority of the studies applying stem cell therapy following MI have demonstrated a decline in fibrosis. However, it was not clearly recognized whether the decline in cardiac fibrosis was due to replacement of dead cardiomyocytes or because of the direct effects of paracrine factors released from the transplanted stem cells on the ECM. Therefore, the main focus of this review is to discuss the impact of different types of stem cells on cardiac fibrosis and associated cardiac remodelling in a variety of experimental models of heart failure, particularly MI.

“…Induced pluripotent stem cells (iPSCs) may be used to treat a number of diseases, as they possess the potential for self-renewal and multi-differentiation ( 6 ). It has previously been suggested that transplanted iPSCs were able to inhibit vascular apoptosis and fibrosis, thus improving cardiac function in diabetic rats ( 7 ). However, little is known about the mechanisms by which iPSCs, or factors released from these cells, inhibit adverse cardiac remodeling ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

Protective effects of human induced pluripotent stem cell‑derived exosomes on high glucose‑induced injury in human endothelial cells

et al. 2018

Exosomes are a family of extracellular vesicles that are secreted from almost all types of cells and are associated with cell-to-cell communication. The present study was performed to investigate the effects of human induced pluripotent stem cell-derived exosomes (hiPSC-exo) on cell viability, capillary-like structure formation and senescence in endothelial cells exposed to high glucose. Exosomes were isolated from the conditional medium of hiPSCs and confirmed by transmission electron microscopy, nanoparticle tracking analysis and western blot analysis using Alix and cluster of differentiation-63 as markers. hiPSC-exo were labeled with PKH26 for tracking, and it was determined that spherical exosomes, with a typical cup-shape, were absorbed by human umbilical vascular endothelial cells (HUVECs). Cultured HUVECs were treated with high glucose (33 mM) with or without hiPSC-exo (20 µg/ml) for 48 h, and cell viability, capillary tube formation and senescence were assessed. When exposed to high glucose, viability and tube formation in HUVECs was significantly reduced (P<0.0001), whereas the proportion of senescent cells was higher compared with that in control HUVECs (P<0.0001). Furthermore, hiPSC-exo restored cell viability and capillary-like structure formation, and reduced senescence in HUVECs exposed to high glucose (P<0.0001). However, hiPSC-exo had minimal effects on normal HUVECs. These findings suggest that stem cell-derived exosomes are able to promote cell proliferation, enhance capillary-like structure formation and reduce senescence in endothelial cells exposed to high glucose.