Bone marrow mesenchymal stem cells attenuate the progression of focal segmental glomerulosclerosis in rat models

Abstract Stroke remains a deadly and disabling disease with limited treatment tragedies due to the limitations of available treatments; novel therapies for stroke are needed. In this article, the synergistic results of dual bone marrow mesenchymal stem cells (BMSC) and fasudil treatment in rat models of ischemic stroke still requires further identification. Sprague-Dawley rats were used to construct the middle cerebral artery, occlusion models. BMSCs were incubated with fasudil, and MTT was performed to evaluate cell proliferation. The rats were treated with fasudil+BMSC, BMSC, fasudil, and saline. Blood samples were collected for complete blood count analysis and measurement of serum TNF-α levels. The neurological functions were evaluated. After the rats were sacrificed, immunohistochemical staining and TTC staining was performed. Fasudil promoted the proliferation of BMSCs and induced their differentiation into neuron-like cells. BMSCs increased the proportion of neutrophils; nevertheless, fasudil counteracted the neutrophil increase. The TUJ-1/MAP2/VIII factor expression in the fasudil+BMSC group was significantly higher than that in the other groups. The number of GFAP-positive cells decreased in the fasudil+BMSC and BMSC alone groups. The infarct volume in the fasudil+BMSC and BMSC alone groups was significantly lower than in the fasudil alone and control groups.Both BMSCs and fasudil exert neurorestorative effects in rat models of cerebral ischemia. Fasudil neutralizes the pro-inflammatory effects of BMSCs, while BMSCs and fasudil together had synergistic effects promoting neurovascular remodeling and neurological function recovery in stroke. A combination of BMSCs and fasudil provides a promising method for the treatment of ischemic stroke.

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High-carbohydrate, High-fat Diet-induced Hyperlipidemia Hampers the Differentiation Balance of Bone Marrow Mesenchymal Stem Cells by Suppressing Autophagy via the AMPK/ mTOR Pathway in Rat Models

10.21203/rs.3.rs-42244/v1 ◽

2020 ◽

Author(s):

Zhenzhen Shang ◽

Ting Zhang ◽

Mengyang Jiang ◽

Xiaojie Yin ◽

Hui Qiang Sun ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Bone Metabolism ◽

High Fat Diet ◽

High Fat ◽

Rat Models ◽

High Carbohydrate ◽

Marrow Mesenchymal Stem Cells

Abstract Background: Disorders of bone metabolism caused by hyperlipidemia is not conducive to osseointegration of implants. Autophagy, an evolutionarily conserved, lysosomal-mediated degradation process, is indispensable for bone homeostasis, its effects on hyperlipidemia-induced osteoporosis remain to be elucidated. The objective of this study was to determine whether autophagy affects bone metabolism and implant osseointegration through regulating the function of bone marrow mesenchymal stem cells (BMMSCs) in rats with hyperlipidemia and to confirm signaling pathway involved in the regulation of autophagy. Methods: Hyperlipidemia models were established through a long-term high-carbohydrate, high-fat diet in 6-week-old male Sprague-Dawley rats. The impact of hyperlipidemia on bone metabolism and early osseointegration of implants was explored by the methods including serum biochemical detection, micro-computed tomography and bone morphology detection. Biological properties and autophagy levels of BMMSCs were also determined. Further, we determined if autophagy was involved in bone metabolism changes resulting from high-fat diet by focusing on the lineage differentiation of BMMSCs. The signaling pathway involved in the regulation of autophagy was also explored.Results: The high-carbohydrate, high-fat diet (HCHF) was given to the rats for seven months aggravated bone loss in the cancellous bone and reduced osseointegration of implants. BMMSCs from hyperlipidemia rats exhibited decreased osteogenesis, increased adipogenesis and decreased autophagic activity compared with regular diet (RD) BMMSCs. Rapamycin treatment restored the impaired osteogenic differentiation and inhibited the adipogenic differentiation of HCHF-BMMSCs through the activation of autophagy. Further, AMPK/mTOR signaling pathways was related to the impairment of autophagy of HCHF-BMMSCs. Conclusions: Our data indicate that long-term high-carbohydrate, high-fat diet-induced hyperlipidemia hampers the differentiation balance of bone marrow mesenchymal stem cells by suppressing autophagy via the AMPK/ mTOR pathway, which ultimately led to aggravated bone loss in the cancellous bone and reduced osseointegration of implants in rat models.

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