Construction of engineered corpus cavernosum with primary mesenchymal stem cells in vitro

Xie, Xiaoxiao; Du, Xiaohang; Li, Kailin; Chen, Yuan; Guan, Yanhua; Zhao, Xiaofei; Niu, Guangzhu; Luan, Yun; Zhang, Denglu; Sun, Chao; Cheng, Guanghui; Wang, Jue; Xin, Qian; Xue, Aibing; Wang, Peng; Kong, Feng; Liu, Xiaoli; Wang, Hongwei; Liu, Yuqiang; Tian, Chen; Yuan, Ming; Liu, Shuangde; Zhao, Shengtian

doi:10.1038/s41598-017-18129-9

Cited by 32 publications

(23 citation statements)

References 39 publications

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“…Chondrogenic differentiation was performed according to ref. [36] with minor modifications. Briefly, 2.5×10 5 WT and mutant cells were left aggregated in microwell plates and then provided with chondrogenic medium containing high-glucose DMEM, 10% FBS, 10 μg/ L TGF-β3, 0.1 μmol/ L dexamethasone, 50 μmol/ L vitamin C, and 6.25 mg/L insulin.…”

Section: Cell Differentiationmentioning

confidence: 99%

Cholinergic-like neurons carrying PSEN1 E280A mutation from familial Alzheimer’s disease reveal intraneuronal sAPPβ fragments accumulation, hyperphosphorylation of TAU, oxidative stress, apoptosis and Ca2+ dysregulation: Therapeutic implications

et al. 2020

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Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive memory loss and cognitive disturbance as a consequence of the loss of cholinergic neurons in the brain, neuritic plaques and hyperphosphorylation of TAU protein. Although the underlying mechanisms leading to these events are unclear, mutations in presenilin 1 (PSEN1), e.g., E280A (PSEN1 E280A), are causative factors for autosomal dominant early-onset familial AD (FAD). Despite advances in the understanding of the physiopathology of AD, there are no efficient therapies to date. Limitations in culturing brain-derived live neurons might explain the limited effectiveness of AD research. Here, we show that mesenchymal stromal (stem) cells (MSCs) can be used to model FAD, providing novel opportunities to study cellular mechanisms and to establish therapeutic strategies. Indeed, we cultured MSCs with the FAD mutation PSEN1 E280A and wild-type (WT) PSEN1 from umbilical cords and characterized the transdifferentiation of these cells into cholinergic-like neurons (ChLNs). PSEN1 E280A ChLNs but not WT PSEN1 ChLNs exhibited increased intracellular soluble amyloid precursor protein (sAPPf) fragments and extracellular Aβ42 peptide and TAU phosphorylation (at residues Ser202/Thr205), recapitulating the molecular pathogenesis of FAD caused by mutant PSEN1. Furthermore, PSEN1 E280A ChLNs presented oxidative stress (OS) as evidenced by the oxidation of DJ-1Cys 106-SH into DJ-1Cys 106-SO 3 and the detection of DCF-positive cells and apoptosis markers such as activated pro-apoptosis proteins p53, c-JUN, PUMA and CASPASE-3 and the concomitant loss of the mitochondrial membrane potential and DNA fragmentation. Additionally, mutant ChLNs displayed Ca 2+ flux dysregulation and deficient acetylcholinesterase (AChE) activity compared to control ChLNs. Interestingly, the inhibitor JNK SP600125 almost completely blocked TAU phosphorylation. Our findings demonstrate that FAD MSC-derived cholinergic neurons with the

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Section: Cell Differentiationmentioning

confidence: 99%

Cholinergic-like neurons carrying PSEN1 E280A mutation from familial Alzheimer’s disease reveal intraneuronal sAPPβ fragments accumulation, hyperphosphorylation of TAU, oxidative stress, apoptosis and Ca2+ dysregulation: Therapeutic implications

et al. 2020

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“…2 c; Supplementary Table S7 ). Changes related to cell death included the induction of genes encoding proteins with proven adverse functions in cardiac muscle cell survival, such as death domain receptors ( TNFRSF8 , TNFRSF10D , TNFRSF18 ) 45 and DNA damage-inducible proteins and growth arrest mediators ( GADD45B , GADD45G ) 46 , 47 . Notable was the upregulation of PMAIP1/NOXA , whose product regulates mitochondrial membrane permeabilization and the release of apoptogens 48 .…”

Section: Resultsmentioning

confidence: 99%

Human pluripotent stem cell-derived cardiomyocytes as a target platform for paracrine protection by cardiac mesenchymal stromal cells

Constantinou

Miranda

Chaves

et al. 2020

Sci Rep

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ischemic heart disease remains the foremost cause of death globally, with survivors at risk for subsequent heart failure. Paradoxically, cell therapies to offset cardiomyocyte loss after ischemic injury improve long-term cardiac function despite a lack of durable engraftment. An evolving consensus, inferred preponderantly from non-human models, is that transplanted cells benefit the heart via early paracrine signals. Here, we tested the impact of paracrine signals on human cardiomyocytes, using human pluripotent stem cell-derived cardiomyocytes (hpSc-cMs) as the target of mouse and human cardiac mesenchymal stromal cells (cMSc) with progenitor-like features. in co-culture and conditioned medium studies, cMScs markedly inhibited human cardiomyocyte death. Little or no protection was conferred by mouse tail tip or human skin fibroblasts. Consistent with the results of transcriptomic profiling, functional analyses showed that the cMSC secretome suppressed apoptosis and preserved cardiac mitochondrial transmembrane potential. protection was independent of exosomes under the conditions tested. in mice, injecting cMSc-conditioned media into the infarct border zone reduced apoptotic cardiomyocytes > 70% locally. Thus, hPSC-CMs provide an auspicious, relevant human platform to investigate extracellular signals for cardiac muscle survival, substantiating human cardioprotection by cMScs, and suggesting the cMSc secretome or its components as potential cell-free therapeutic products. The paramount public health burden of ischemic heart disease 1 and the dearth of restorative growth in adult mammalian myocardium have, together, given focus to maintaining cardiomyocyte number as a therapeutic target 2,3. If successful, this would transform the scope of treatment for ischemic heart disease, beyond merely reperfusion to restore coronary flow. Proposed approaches include diverse cell therapies aimed at the generation of new cardiac muscle, by grafting putative precursors such as bone marrow stem cells, heart-derived cardiac progenitor/stem cells, cardiac mesenchymal cells, cardiosphere-derived cells, and established cardiomyocytes made from pluripotent stem cells 2,3. However, the persistence of grafted cells in recipient hearts is brief, at least in the pre-clinical setting where it can be tracked conclusively, leading to a persuasive twofold paradigm shift 4-13. First, therapeutic grafting to supply de novo contractile myocytes themselves is now understood to require alternatives beyond simplistic injections of naked cells, an aspect ripe for biomaterials and tissue engineering

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“…The total RNA was extracted from each renal tissue using RNAprep Pure Tissue Kit (Tiangen Biotech, Guangzhou, China) according to the manufacturer’s protocol and reverse transcribed into the first-strand cDNA which was synthesized from 500 ng total RNA and 5× primescript RT Master Mix 2 μL (Takara Bio INC., Kusatsu, Japan) in a 10 μL reaction volume, and then, amplified by the PCR reactions using GoTaqR qPCR Master Mix, 2X (Promega Corporation, Madison, USA), primers of TGF-β1, α-SMA, Glut-1, GAPDH, IL-1β, TNF-α and IL-6 (designed and synthesized by Suzhou Hongxun Biological Co., Ltd.; Table 1 , [ 37 – 40 ]), and RNase-free ddH 2 O in a 10 μL reaction volume using Applied Biosystems ® 7500 Fast Real-time PCR System (Thermo Fisher Scientific, USA) under the following reaction conditions: 50.0 °C for 3 min and 95.0 °C for 3 min, followed by 40 cycles at 95.0 °C for 10 s and 60.0 °C for 30 s. The threshold cycle (Ct) was recorded by the instrument’s software (7500 Fast System Software version v2.3), and the fold changes in the mRNA expression were calculated according to the comparative Ct method (2 −ΔΔCT ) as presented.…”

Section: Methodsmentioning

confidence: 99%

Codonopsis tangshen Oliv. Amelioration Effect on Diabetic Kidney Disease Rats Induced by High Fat Diet Feeding Combined with Streptozotocin

Zhou

Dong

et al. 2018

Nat. Prod. Bioprospect.

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Diabetic kidney disease (DKD) is the most serious microvascular complication during the development of diabetes with the characterizations of glomerular basement membrane thickening, mesangial expansion, and glomerular sclerosis, eventually leading to end-stage renal disease. This study aimed to investigate the melioration effect of Codonopisis tangshen Oliv. (COD) on the DKD model, which was established by unilateral nephrectomy (UN)-high fat diet feeding (HFD) combined with streptozotocin (STZ). After the DKD rats were oral treated with COD at a dose of 2.7 mg/kg for 4 consecutive weeks, the blood glucose, lipid metabolism, renal function, inflammatory mediators, and fibrosis-associated proteins were examined. In vivo, the COD administration obviously relieved the weight loss, water intake, and blood glucose; decreased the total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels; and improved the renal function by reducing the expression of serum creatinine, uric acid, and urinary protein compared with the model group. The levels of pro-inflammatory cytokines of tumor necrosis factor-α, interleukin-1β, and IL-6 were significantly inhibited by COD. Meanwhile, the deposition of collagen fiber was markedly increased, and the protein and mRNA expressions of transforming growth factor-β1 and α-smooth muscle actin were markedly elevated in DKD rats, but they were decreased to some extent after the COD treatment. In conclusion, COD exhibited a protective effect on the UN-HFD feeding combined with STZ-induced DKD model by improving the blood glucose and lipid metabolism, relieving the inflammatory response, and mitigating the renal fibrosis, which provided scientific evidence for its applications in clinic.Graphical Abstract

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Construction of engineered corpus cavernosum with primary mesenchymal stem cells in vitro

Cited by 32 publications

References 39 publications

Cholinergic-like neurons carrying PSEN1 E280A mutation from familial Alzheimer’s disease reveal intraneuronal sAPPβ fragments accumulation, hyperphosphorylation of TAU, oxidative stress, apoptosis and Ca2+ dysregulation: Therapeutic implications

Cholinergic-like neurons carrying PSEN1 E280A mutation from familial Alzheimer’s disease reveal intraneuronal sAPPβ fragments accumulation, hyperphosphorylation of TAU, oxidative stress, apoptosis and Ca2+ dysregulation: Therapeutic implications

Human pluripotent stem cell-derived cardiomyocytes as a target platform for paracrine protection by cardiac mesenchymal stromal cells

Codonopsis tangshen Oliv. Amelioration Effect on Diabetic Kidney Disease Rats Induced by High Fat Diet Feeding Combined with Streptozotocin

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