Induced autologous stem cell transplantation for treatment of rabbit renal interstitial fibrosis.

INTRODUCTION: Renal interstitial fibrosis (RIF) is a significant cause of end-stage renal failure. The goal of this study was to characterize the distribution of transplanted induced autologous stem cells in a rabbit model of renal interstitial fibrosis and evaluate its therapeutic efficacy for treatment of renal interstitial fibrosis. METHODS: A rabbit model of renal interstitial fibrosis was established. Autologous fibroblasts were cultured, induced and labeled with green fluorescent protein (GFP). These labeled stem cells were transplanted into the renal artery of model animals at 8 weeks. RESULTS: Eight weeks following transplantation of induced autologous stem cells, significant reductions (P < 0.05) were observed in serum creatinine (SCr) (14.8 ± 1.9 mmol/L to 10.1 ± 2.1 mmol/L) and blood urea nitrogen (BUN) (119 ± 22 µmol/L to 97 ± 13 µmol/L), indicating improvement in renal function. CONCLUSIONS: We successfully established a rabbit model of renal interstitial fibrosis and demonstrated that transplantation of induced autologous stem cells can repair kidney damage within 8 weeks. The repair occurred by both inhibition of further development of renal interstitial fibrosis and partial reversal of pre-existing renal interstitial fibrosis. These beneficial effects lead to the development of normal tissue structure and improved renal function.

Reprogrammed peripheral blood mononuclear cells are able to survive longer in irradiated female mice.

Induced multipotent stem (iMS) cells are originated from somatic cells and become multipotent by genetic and/or epigenetic modifications. Previous studies have shown that the fish oocytes extracts (FOE) can induce skin fibroblast cells into iMS cells. In this study, we aim to determine whether FOE can similarly induce mouse peripheral blood mononuclear cells (PBMCs) into the iMS state and if so, whether they can survive longer when they are transplanted into the irradiation female mice. PBMCs of GFP-transgenic male mice were cultured and transiently reprogrammed by FOE. They were deemed reaching the iMS state after detection of expression of stem cell markers. The iMS-like PBMCs were transplanted into female C57BL mice by tail vein injection. The spleen wet weights as well as numbers of colonies of the recipient mice were examined. The results showed the spleen wet weights and numbers of spleen colonies of FOE-induced group were all significantly higher than those of the non-induced group and negative control group. On day 90 after transplantation, FISH analysis detected the presence of Y chromosome in the induced group, but not of the other groups. The current findings demonstrate that FOE-induced PBMCs are able to survive longer in irradiated female mice.

Comparative study among three different methods of bone marrow mesenchymal stem cell transplantation following cerebral infarction in rats.

The objective of this study was to investigate the effects of transplanted bone marrow mesenchymal stem cells (BMSCs) administered via internal jugular vein injection, carotid artery injection, or intraventricular transplantation for the treatment of cerebral infarction, which was modeled in rats. The neurological scores of the treated rats and the distribution of the transplanted cells (GFP-labeled) in the infarction area were evaluated. The cerebral infarction model was produced by inserting a modified Zea-longa suture, which generated middle cerebral artery occlusion (MCAO). The GFP-labeled BMSCs were transplanted through the jugular vein or the carotid artery or by stereotactic intraventricular delivery to the infarction models 1 week after the cerebral infarction was established. The 'Nerve Function Score' of the model rats was recorded before and after BMSC transplantation. Brain tissue sections were examined under a fluorescence microscope. We determined that the transplanted BMSCs rescued brain function, which was indicated by a decrease in the neurological scores (P<0·05) following BMSC transplantation. The effect of BMSC transplantation was reflected in decreases in the neurological score in the intraventricular transplantation group, the carotid artery transplantation group, and the jugular vein graft group*. The transplanted BMSCs were able to migrate to the brain injury area and the cortex and survived the infarction; thus, BMSCs may promote the recovery of nerve function.

Induced autologous stem cell transplantation for treatment of rabbit type 1 diabetes.

We have examined the effects of induced autologous stem cells on blood sugar levels in a rabbit model of type 1 diabetes. Rabbit skin fibroblasts were induced to dedifferentiate into multipotent stem cells, and were transplanted into the treatment group via the pancreatic artery. After the fibroblasts had been induced for 72 h, some of them became multipotent stem cells. Four weeks after cell transplantation, blood glucose levels of the induced stem cell treatment group were significantly lower. The plasma insulin and plasma C-peptide levels of the treated group were significantly increased (P < 0.05). The shape and number of islets was different. In the control group, induced cell treatment group and non-induced cell treatment group. In the control group, islet ß-cell nucleoli were obvious, and cell volumes were larger with more abundant cytoplasm. The rough endoplasmic reticulum was well-developed and a large number of secretory granules could be seen within the cytoplasm. In the induced cell treatment group, islet ß cells were scattered, and their nuclei were oval and slightly irregular in shape. The cytoplasm of these cells contained a nearly normal number of secretory granules. In the non-induced cell treatment group, islet ß-cells were atrophied and cell volumes were reduced. Cytoplasmic endocrine granules were significantly reduced or absent. In conclusion, treatment with induced multipotent stem cells can reduce blood sugar levels, improve islet cell function, and repair damaged pancreas in a rabbit model of type 1 diabetes.