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Platelet-rich plasma enhances adipose-derived stem cell-mediated angiogenesis in a mouse ischemic hindlimb model

World Journal of Stem Cells 2018年第12期10卷 212-227页

作者： Chia-Fang Chen Han-Tsung Liao Department of Plastic and Reconstructive Surgery Chang Gung Memorial Hospital Craniofacial Research Center Chang Gung Memorial Hospital College of Medicine Chang Gung University

AIM To evaluate the angiogenic effect of platelet-rich plasma(PRP)-preconditioned adipose-derived stem cells(ADSCs) both in vitro and in a mouse ischemic hindlimb *** ADSCs were divided based on culture medium: 2.5% PRP, 5% PRP, 7.5% PRP, and 10% PRP. Cell proliferation rate was analyzed using the MTS assay. The gene expression of CD31, vascular endothelial growth factor, hypoxia-inducible factors, and endothelial cell nitric oxide synthase was analyzed using reverse transcription polymerase chain reaction. Cell markers and structural changes were assessed through immunofluorescence staining and the tube formation assay. Subsequently, we studied the in vivo angiogenic capabilities of ADSCs by a mouse ischemic hindlimb *** The proliferation rate of ADSCs was higher in the 2.5%, 5%, and 7.5% PRP groups. The expression of hypoxia-inducible factor, CD31, vascular endothelial growth factor, and endothelial cell nitric oxide synthase in the 5% and 7.5% PRP groups increased. The 5%, 7.5%, and 10% PRP groups showed higher abilities to promote both CD31 and vascular endothelial growth factor production and tubular structure formation in ADSCs. According to laser Doppler perfusion scan, the perfusion ratios of ischemic limb to normal limb were significantly higher in 5% PRP, 7.5% PRP, and human umbilical vein endothelial cells groups compared with the negative control and fetal bovine serum(FBS) groups(0.88 ± 0.08, 0.85 ± 0.07 and 0.81 ± 0.06 for 5%, 7.5% PRP and human umbilical vein endothelial cells compared with 0.42 ± 0.17 and 0.54 ± 0.14 for the negative control and FBS, P hindlimbs. The optimal angiogenic effect occurred in 5% PRP-and 7.5% PRPpreconditioned ADSCs.

关键词： Platelet-rich plasma Adipose-derived stem cells Mesenchymal stem cell Angiogenesis Endothelial differentiation Mouse ischemic hindlimb model

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Endochondral ossification of hindlimbs in embryonic development of Japanese Quail(Coturnix japonica)

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Avian Research 2024年第1期15卷 123-132页

作者： Xuan Li Yuxin Zhang Hongfeng Zhao College of Life Sciences Shaanxi Normal UniversityXi’an710119China

The endochondral ossification of hindlimb is essential to a bird’s ability to stand,walk and *** hindlimb is ossified in the embryos before hatching in precocial ***,the molecular mechanisms of hindlimb ossification in birds is still ***,we tried to examine the process of hindlimb ossification and its molecular regulation by using an animal model—Japanese Quail(Coturnix japonica).We selected four critical stages(Embryo Day:E6,E8,E12 and E16) of skeletal development of embryonic quails for hindlimb skeleton staining to show the process of endochondral ossification and to examine the molecular regulation of endochondral osteogenesis by RNA-Seq *** results showed that ossification became increased with embryonic development and most hindlimb was ossified before ***-Seq analysis revealed that various signaling pathways were involved with endochondral ossification with thyroid hormone signaling and WNT signaling pathway particularly ***,the expression levels of 42 genes were continuously upregulated and 14 genes were continuously downregulated from E6 to *** present study might provide new insights into complex molecular mechanisms in regulation of endochondral ossification.

关键词： Embryos hindlimb Ossification Precocial Transcriptomics

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Matrine promotes neural circuit remodeling to regulate motor function in a mouse model of chronic spinal cord injury

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Neural Regeneration Research 2019年第11期14卷 1961-1967页

作者： Norio Tanabe Tomoharu Kuboyama Chihiro Tohda Division of Neuromedical Science Institute of Natural Medicine University of Toyama

In chronic phase of spinal cord injury, functional recovery is more untreatable compared with early intervention in acute phase of spinal cord injury. In the last decade, several combination therapies successfully improved motor dysfunction in chronic spinal cord injury. However, their effectiveness is not sufficient. We previously found a new effective compound for spinal cord injury, matrine, which induced axonal growth and functional recovery in acute spinal cord injury mice via direct activation of extracellular heat shock protein 90. Although our previous study clarified that matrine was an activator of extracellular heat shock protein 90, the potential of matrine for spinal cord injury in chronic phase has not been sufficiently evaluated. Thus, this study aimed to investigate whether matrine ameliorates chronic spinal cord injury in mice. Once daily intragastric administration of matrine(100 μmol/kg per day) to spinal cord injury mice were starte at 28 days after injury, and continued for 154 days. Continuous mat rine treatment improved hindlimb motor function in chronic spinal cord injury mice. In injured spinal cords of the matrine-treated mice, the density of neurofilament-H-positive axons was increased. Moreover, matrine treatment increased the density of bassoon-positive presynapses in contact with choline acetyltransferase-positive motor neurons in the lumbar spinal cord. These findings suggest that matrine promotes remodeling and reconnection of neural circuits to regulate hindlimb movement. All protocols were approved by the Committee for Animal Care and Use of the Sugitani Campus of the University of Toyama(approval No. A2013 INM-1 and A2016 INM-3) on May 7, 2013 and May 17, 2016, respectively.

关键词： matrine chronic spinal cord injury axonal growth synaptogenesis hindlimb locomotor presynapse immunohistochemistry Basso Mouse Scale Body Support Score Sophora flavescens

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From cortex to cord: motor circuit plasticity after spinal cord injury

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Neural Regeneration Research 2019年第12期14卷 2054-2062页

作者： Andrew R. Brown Marina Martinez Département de Neurosciences Facultéde MédecineUniversitéde MontréalQuébecCanada H?pital du Sacré-Coeur de Montréal(CIUSS-NIM) MontréalQuébecCanada Groupe de Recherche sur le Système Nerveux Central Universitéde MontréalMontréalQuébecCanada

Spinal cord injury is associated with chronic sensorimotor deficits due to the interruption of ascending and descending tracts between the brain and spinal cord. Functional recovery after anatomically complete spinal cord injury is limited due to the lack of long-distance axonal regeneration of severed fibers in the adult central nervous system. Most spinal cord injuries in humans, however, are anatomically incomplete. Although restorative treatment options for spinal cord injury remain currently limited, research from experimental models of spinal cord injury have revealed a tremendous capability for both spontaneous and treatment-induced plasticity of the corticospinal system that supports functional recovery. We review recent advances in the understanding of corticospinal circuit plasticity after spinal cord injury and concentrate mainly on the hindlimb motor cortex, its corticospinal projections, and the role of spinal mechanisms that support locomotor recovery. First, we discuss plasticity that occurs at the level of motor cortex and the reorganization of cortical movement representations. Next, we explore downstream plasticity in corticospinal projections. We then review the role of spinal mechanisms in locomotor recovery. We conclude with a perspective on harnessing neuroplasticity with therapeutic interventions to promote functional recovery.

关键词： spinal cord injury motor cortex motor map corticospinal tract neuroplasticity functionalrecovery animal models forelimb hindlimb locomotion

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Therapeutic neovascularization by autologous transplantation with expanded endothelial progenitor cells from peripheral blood into ischemic hind limbs

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Acta Pharmacologica Sinica 2005年第9期26卷 1069-1075页

作者： Chun-ling FAN Ping-jin GAO Zai-qian CHE Jian-jun LIU Jian WEI Ding-liang ZHU~2 Shanghai Key Laboratory Of Vascular Biology,Shanghai Institute of Hypertension,Ruijin Hospital,Shanghai Second Medical University and National Key Laboratory for Medical Genomics,Health Science Center,Shanghai Institute for Biological Sciences,Chinese Academy of Sciences,Shanghai 200025,China Shanghai Key Laboratory of Vascular Biology Shanghai Institute of Hypertension Ruijin Hospital Shanghai Second Medical University and National Key Laboratory for Medical Genomics Health Science Center Shanghai Institute for Biological Sciences Chinese Academy of Sciences Shanghai China

Aim:To investigate the hypothesis that transplantation with expanded autolo-gous endothelial progenitor cells(EPC)could enhance ***:Peripheral blood mononuclear cells(PB-MNC)isolated from New ZealandWhite rabbits were cultured in *** d 7,the adherent cells were collected forautologous *** with severe unilateral hind limb ischemiawere randomly assigned to receive phosphate-buffered saline or expanded EPC inphosphate-buffered saline,administered by intramuscular injection in 6 sites ofthe ischemic thigh at postoperative d *** was monitored byusing the calf blood pressure ratio to indicate tissue perfusion,digital subtractionangiography to identify collateral vessel development and histological analysisof capillary density in the ischemic limb at d 35 after ***:Autolo-gous EPC transplantation produced significant amelioration in ischemic hind limbs,as indicated by a greater calf blood pressure ratio(0.52±0.04 vs 0.42±0.05,Phindlimbs.

关键词： vascular endothelium hindlimb ischemia physiologic neovascularization stem cell transplantation

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Adipose tissue-derived stem cells as a therapeutic tool for cardiovascular disease

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World Journal of Cardiology 2015年第8期7卷 454-465页

作者： Etsu Suzuki Daishi Fujita Masao Takahashi Shigeyoshi Oba Hiroaki Nishimatsu Institute of Medical Science St. Marianna University School of Medicine the Department of Internal Medicine Faculty of Medicine University of Tokyo the Department of Urology Faculty of Medicine University of Tokyo

Adipose tissue-deried stem cells( ADSCs) are adult stem cells that can be easily harvested from subcutaneous adipose tissue. Many studies have demonstrated that ADSCs differentiate into vascular endothelial cells(VECs), vascular smooth muscle cells(VSMCs), and cardiomyocytes in vitro and in vivo. However, ADSCs may fuse with tissue-resident cells and obtain the corresponding characteristics of those cells. If fusion occurs, ADSCs may express markers of VECs, VSMCs, and cardiomyocytes without direct differentiation into these cell types. ADSCs also produce a variety of paracrine factors such as vascular endothelial growth factor, hepatocyte growth factor, and insulin-like growth factor-1 that have proangiogenic and/or antiapoptotic activities. Thus, ADSCs have the potential to regenerate the cardiovascular system via direct differentiation into VECs, VSMCs, and cardiomyocytes, fusion with tissueresident cells, and the production of paracrine factors. Numerous animal studies have demonstrated the efficacy of ADSC implantation in the treatment of acute myocardial infarction(AMI), ischemic cardiomyopathy(ICM), dilated cardiomyopathy, hindlimb ischemia, and stroke. Clinical studies regarding the use of autologous ADSCs for treating patients with AMI and ICM have recently been initiated. ADSC implantation has been reported as safe and effective so far. Therefore, ADSCs appear to be useful for the treatment of cardiovascular disease. However, the tumorigenic potential of ADSCs requires careful evaluation before their safe clinical application.

关键词： Adipose tissue-derived stem cells Cardio-vascular disease Acute myocardial infarction Ischemic cardiomyopathy hindlimb ischemia Stroke

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