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NELL-1

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https://www.readbyqxmd.com/read/28629047/two-phase-electrospinning-to-incorporate-growth-factors-loaded-chitosan-nanoparticles-into-electrospun-fibrous-scaffolds-for-bioactivity-retention-and-cartilage-regeneration
#1
Chongyang Wang, Wenxiu Hou, Xuran Guo, Juehong Li, Tu Hu, Manle Qiu, Shen Liu, Xiumei Mo, Xudong Liu
Growth factor is an essential ingredient to regulate mesenchymal stem cells (MSCs) chondrogenic differentiation in cartilage tissue engineering. However, non-osteochondral specification, short plasma half time and bioactivity loss restrict growth factor's application. Thus, novel chondrogenic growth factors, specifically target osteochondral lineage cells, that can be sustained release and bioactivity protected to exert functions continually and effectively have attracted increasing researchers' interest. To achieve these goals, chitosan nanoparticles and electrospun fiber scaffolds were used as dual release system to sustain release Nel-like molecule-1 (Nell-1) growth factor and protect bioactivity, then the effect and mechanism of Nell-1 on inducing human bone MSCs (hBMSCs) differentiate toward chondrocytes were investigated...
October 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28614787/nell-1-induces-sca-1-mesenchymal-progenitor-cell-expansion-in-models-of-bone-maintenance-and-repair
#2
Aaron W James, Jia Shen, Rebecca Tsuei, Alan Nguyen, Kevork Khadarian, Carolyn A Meyers, Hsin Chuan Pan, Weiming Li, Jin H Kwak, Greg Asatrian, Cymbeline T Culiat, Min Lee, Kang Ting, Xinli Zhang, Chia Soo
NELL-1 is a secreted, osteogenic protein first discovered to control ossification of the cranial skeleton. Recently, NELL-1 has been implicated in bone maintenance. However, the cellular determinants of NELL-1's bone-forming effects are still unknown. Here, recombinant human NELL-1 (rhNELL-1) implantation was examined in a clinically relevant nonhuman primate lumbar spinal fusion model. Prolonged rhNELL-1 protein release was achieved using an apatite-coated β-tricalcium phosphate carrier, resulting in a local influx of stem cell antigen-1-positive (Sca-1+) mesenchymal progenitor cells (MPCs), and complete osseous fusion across all samples (100% spinal fusion rate)...
June 15, 2017: JCI Insight
https://www.readbyqxmd.com/read/28514897/biomaterials-and-bioactive-agents-in-spinal-fusion
#3
Rui M Duarte, Pedro Varanda, Rui L Reis, Ana Rita C Duarte, Jorge Correia-Pinto
Management of degenerative spine pathologies frequently leads to the need for spinal fusion (SF), where bone growth is induced toward stabilization of the interventioned spine. Autologous bone graft (ABG) remains the gold-standard inducer, whereas new bone graft substitutes attempt to achieve effective de novo bone formation and solid fusion. Limited fusion outcomes have driven motivation for more sophisticated and multidisciplinary solutions, involving new biomaterials and/or biologics, through innovative delivery platforms...
June 28, 2017: Tissue Engineering. Part B, Reviews
https://www.readbyqxmd.com/read/28489940/isolation-and-characterization-of-canine-perivascular-stem-stromal-cells-for-bone-tissue-engineering
#4
Aaron W James, Xinli Zhang, Mihaela Crisan, Winters R Hardy, Pei Liang, Carolyn A Meyers, Sonja Lobo, Venu Lagishetty, Martin K Childers, Greg Asatrian, Catherine Ding, Yu-Hsin Yen, Erin Zou, Kang Ting, Bruno Peault, Chia Soo
For over 15 years, human subcutaneous adipose tissue has been recognized as a rich source of tissue resident mesenchymal stem/stromal cells (MSC). The isolation of perivascular progenitor cells from human adipose tissue by a cell sorting strategy was first published in 2008. Since this time, the interest in using pericytes and related perivascular stem/stromal cell (PSC) populations for tissue engineering has significantly increased. Here, we describe a set of experiments identifying, isolating and characterizing PSC from canine tissue (N = 12 canine adipose tissue samples)...
2017: PloS One
https://www.readbyqxmd.com/read/28463604/nell-1-hmgb1-and-ccn2-enhance-migration-and-vasculogenesis-but-not-osteogenic-differentiation-compared-to-bmp2
#5
Shorouk Fahmy-Garcia, Marjolein van Driel, Janneke Witte-Buoma, Heike Walles, Johannes Ptm van Leeuwen, Gerjo van Osch, Eric Farrell
Currently, autografts still represent the gold standard treatment for the repair of large bone defects. However, these are associated with donor site morbidity, increased pain, cost and recovery time. The ideal therapy would use biomaterials combined with bone growth factors to induce and instruct bone defect repair without the need to harvest patient tissue. In this line, BMPs have been the most extensively used agents for clinical bone repair, but at supraphysiological doses that are not without risk. Because of the need to eliminate the risks of BMP2 use in vivo, we assessed the ability of three putative osteogenic factors, Nell-1, HMGB1 and CCN2, to enhance the essential processes for bone defect repair in vitro and compared them to BMP2...
May 2, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28302495/neural-egfl-like-1-is-a-downstream-regulator-of-runt-related-transcription-factor-2-in-chondrogenic-differentiation-and-maturation
#6
Chenshuang Li, Jie Jiang, Zhong Zheng, Kevin S Lee, Yanheng Zhou, Eric Chen, Cymbeline T Culiat, Yiqiang Qiao, Xuepeng Chen, Kang Ting, Xinli Zhang, Chia Soo
Recent studies indicate that neural EGFL-like 1 (Nell-1), a secretive extracellular matrix molecule, is involved in chondrogenic differentiation. Herein, we demonstrated that Nell-1 serves as a key downstream target of runt-related transcription factor 2 (Runx2), a central regulator of chondrogenesis. Unlike in osteoblast lineage cells where Nell-1 and Runx2 demonstrate mutual regulation, further studies in chondrocytes revealed that Runx2 tightly regulates the expression of Nell-1; however, Nell-1 does not alter the expression of Runx2...
May 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28198775/combining-smoothened-agonist-and-nel-like-protein-1-enhances-bone-healing
#7
Soonchul Lee, Chenchao Wang, Hsin Chuan Pan, Swati Shrestha, Carolyn Meyers, Catherine Ding, Jia Shen, Eric Chen, Min Lee, Chia Soo, Kang Ting, Aaron W James
BACKGROUND: Nonhealing bone defects represent an immense biomedical burden. Despite recent advances in protein-based bone regeneration, safety concerns over bone morphogenetic protein-2 have prompted the search for alternative factors. Previously, the authors examined the additive/synergistic effects of hedgehog and Nel-like protein-1 (NELL-1) on the osteogenic differentiation of mesenchymal stem cells in vitro. In this study, the authors sought to leverage their previous findings by applying the combination of Smoothened agonist (SAG), hedgehog signal activator, and NELL-1 to an in vivo critical-size bone defect model...
June 2017: Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/27585207/polyelectrolyte-complex-for-heparin-binding-domain-osteogenic-growth-factor-delivery
#8
Raymond Wing Moon Lam, Sunny Akogwu Abbah, Wang Ming, Mathanapriya Naidu, Felly Ng, Hu Tao, James Goh Cho Hong, Kang Ting, Wong Hee Kit
During reconstructive bone surgeries, supraphysiological amounts of growth factors are empirically loaded onto scaffolds to promote successful bone fusion. Large doses of highly potent biological agents are required due to growth factor instability as a result of rapid enzymatic degradation as well as carrier inefficiencies in localizing sufficient amounts of growth factor at implant sites. Hence, strategies that prolong the stability of growth factors such as BMP-2/NELL-1, and control their release could actually lower their efficacious dose and thus reduce the need for larger doses during future bone regeneration surgeries...
2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27354930/efficacy-of-intraperitoneal-administration-of-pegylated-nell-1-for-bone-formation
#9
Justine Tanjaya, Yulong Zhang, Soonchul Lee, Jiayu Shi, Eric Chen, Pia Ang, Xinli Zhang, Sotirios Tetradis, Kang Ting, Benjamin Wu, Chia Soo, Jin Hee Kwak
Systemically delivered NEL-like molecule-1 (NELL-1), a potent pro-osteogenic protein, promotes bone formation in healthy and osteoporotic mouse models. PEGylation of NELL-1 (NELL-PEG) increases the half-life of the protein in a mouse model without compromising its osteogenic potential, thereby improving its pharmacokinetics upon systemic delivery. This study consists of a twofold approach: a biodistribution test and an in vivo osteogenic potential test. The biodistribution test compared two commonly used administration methods for drug delivery other than intravenous-intraperitoneal (IP) and subcutaneous (SC)-to examine NELL-PEG biodistribution in mice...
2016: BioResearch Open Access
https://www.readbyqxmd.com/read/27349789/controlled-release-of-nell-1-protein-from-chitosan-hydroxyapatite-modified-tcp-particles
#10
Yulong Zhang, Rui Dong, Yujin Park, Marc Bohner, Xinli Zhang, Kang Ting, Chia Soo, Benjamin M Wu
NEL-like molecule-1 (NELL-1) is a novel osteogenic protein that showing high specificity to osteochondral cells. It was widely used in bone regeneration research by loading onto carriers such as tricalcium phosphate (TCP) particles. However, there has been little research on protein controlled release from this material and its potential application. In this study, TCP was first modified with a hydroxyapatite coating followed by a chitosan coating to prepare chitosan/hydroxyapatite-coated TCP particles (Chi/HA-TCP)...
September 10, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/27113550/vertebral-implantation-of-nell-1-enhances-bone-formation-in-an-osteoporotic-sheep-model
#11
Aaron W James, Michael Chiang, Greg Asatrian, Jia Shen, Raghav Goyal, Choon G Chung, Le Chang, Swati Shrestha, A Simon Turner, Howard B Seim, Xinli Zhang, Benjamin M Wu, Kang Ting, Chia Soo
BACKGROUND: Vertebral compression fractures related to osteoporosis greatly afflict the aging population. One of the most commonly used therapy today is balloon kyphoplasty. However, this treatment is far from ideal and is associated with significant side effects. NELL-1, an osteoinductive factor that possesses both pro-osteogenic and anti-osteoclastic properties, is a promising candidate for an alternative to current treatment modalities. This study utilizes the pro-osteogenic properties of recombinant human NELL-1 (rhNELL-1) in lumbar spine vertebral defect model in osteoporotic sheep...
June 2016: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/27080300/-nell-1-a-novel-highly-efficient-and-specific-growth-factor
#12
REVIEW
X Y Qin, H X Zhao, Q Zhang, F Chen, J X Lin
Regeneration of bone tissue, as well as other tissues, requires involvement and interaction of cells, scaffolds and relevant growth factors, among which growth factors play a crucial role in maintaining the stability of microenvironment. Nel-like-type 1 molecule (NELL-1), a novel growth factor in tissue engineering, has been studied intensively in recent years. Researches mainly covered gene and protein structure and their expression profiling, biological function, molecular mechanisms and disease relevance...
April 18, 2016: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/27047227/nell-1-expression-in-tumors-of-cartilage
#13
Jia Shen, Gregory LaChaud, Swati Shrestha, Greg Asatrian, Xinli Zhang, Sarah M Dry, Chia Soo, Kang Ting, Aaron W James
BACKGROUND/AIMS: NELL-1 is a novel osteochondral differentiation factor protein with increasing usage in tissue engineering. Previously, we reported the expression patterns of NELL-1 in bone-forming skeletal tumors. With increasing interest in the use of NELL-1 protein, we sought to examine the expression of NELL-1 in cartilage-forming tumors. METHODS: Immunohistochemical expression was examined in human pathologic specimens. RESULTS: Consistent NELL-1 overexpression across all cartilage-forming tumors was observed...
December 2015: Journal of Orthopaedics
https://www.readbyqxmd.com/read/26772960/novel-wnt-regulator-nel-like-molecule-1-antagonizes-adipogenesis-and-augments-osteogenesis-induced-by-bone-morphogenetic-protein-2
#14
Jia Shen, Aaron W James, Xinli Zhang, Shen Pang, Janette N Zara, Greg Asatrian, Michael Chiang, Min Lee, Kevork Khadarian, Alan Nguyen, Kevin S Lee, Ronald K Siu, Sotirios Tetradis, Kang Ting, Chia Soo
The differentiation factor NEL-like molecule-1 (NELL-1) has been reported as osteoinductive in multiple in vivo preclinical models. Bone morphogenetic protein (BMP)-2 is used clinically for skeletal repair, but in vivo administration can induce abnormal, adipose-filled, poor-quality bone. We demonstrate that NELL-1 combined with BMP2 significantly optimizes osteogenesis in a rodent femoral segmental defect model by minimizing the formation of BMP2-induced adipose-filled cystlike bone. In vitro studies using the mouse bone marrow stromal cell line M2-10B4 and human primary bone marrow stromal cells have confirmed that NELL-1 enhances BMP2-induced osteogenesis and inhibits BMP2-induced adipogenesis...
February 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/26700847/accelerated-chondrogenic-differentiation-of-human-perivascular-stem-cells-with-nell-1
#15
Chen-Shuang Li, Xinli Zhang, Bruno Péault, Jie Jiang, Kang Ting, Chia Soo, Yan-Heng Zhou
Osteoarthritis is the leading cause of disability in the US. Consequently, there is a pressing need for restoring the structural and functional properties of diseased articular cartilage. Yet the search for the right combination of proper target cells and growth factors for cartilage regeneration remains challenging. In this study, we first tested the intrinsic chondrogenic differentiation ability of human perivascular stem cells (hPSCs), a novel source of mesenchymal stem cells (MSCs) isolated by fluorescence-activated cell sorting (FACS) from human adipose tissue...
February 2016: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/26456257/nel-like-molecule-1-contributes-to-the-odontoblastic-differentiation-of-human-dental-pulp-cells
#16
Mengmeng Liu, Qiang Wang, Ronghua Tang, Rongyu Cao, Xiaoying Wang
INTRODUCTION: Nel-like molecule-1 (Nell-1) with epidermal cell growth factor-like coding structures is a recently discovered secreted protein that can specifically induce osteoblast differentiation, bone formation, and bone regeneration. The expression and localization of Nell-1 during murine molar development suggest that this protein participates in odontoblastic differentiation. This study aims to assess the expression of Nell-1 in the pulp-dentin complex of human teeth and determine the effect of human recombinant Nell-1 (hrNell-1) on odontoblastic differentiation of cultured human dental pulp cells...
January 2016: Journal of Endodontics
https://www.readbyqxmd.com/read/26173400/brief-report-human-perivascular-stem-cells-and-nel-like-protein-1-synergistically-enhance-spinal-fusion-in-osteoporotic-rats
#17
Soonchul Lee, Xinli Zhang, Jia Shen, Aaron W James, Choon G Chung, Reef Hardy, Chenshuang Li, Caroline Girgius, Yulong Zhang, David Stoker, Huiming Wang, Benjamin M Wu, Bruno Peault, Kang Ting, Chia Soo
Autologous bone grafts (ABGs) are considered as the gold standard for spinal fusion. However, osteoporotic patients are poor candidates for ABGs due to limited osteogenic stem cell numbers and function of the bone microenvironment. There is a need for stem cell-based spinal fusion of proven efficacy under either osteoporotic or nonosteoporotic conditions. The purpose of this study is to determine the efficacy of human perivascular stem cells (hPSCs), a population of mesenchymal stem cells isolated from adipose tissue, in the presence and absence of NELL-1, an osteogenic protein, for spinal fusion in the osteoporosis...
October 2015: Stem Cells
https://www.readbyqxmd.com/read/26090379/maldi-tof-mass-array-analysis-of-nell-1-promoter-methylation-patterns-in-human-gastric-cancer
#18
Changlu Gao, Qian Zhang, Deyang Kong, Di Wu, Changlei Su, Jinxue Tong, Feng Chen, Qifan Zhang
Mass spectrometry (MS) enables rapid and sensitive qualitative and quantitative analyses of biomolecules (proteins, peptides, oligosaccharides, lipids, DNA, and RNA), drugs, and metabolites. MS has become an essential tool in modern biomedical research, including the analysis of DNA methylation. DNA methylation has been reported in many cancers, suggesting that it can be utilized as an early biomarker to improve the early diagnosis rate. Using matrix-assisted laser desorption/ionization time-of-flight MS and MassCLEAVE reagent, we compared Nell-1 hypermethylation levels among tumor tissues, paracarcinoma tissues, and normal tissues from gastric cancer patients...
2015: BioMed Research International
https://www.readbyqxmd.com/read/26082355/nell-1-in-the-treatment-of-osteoporotic-bone-loss
#19
Aaron W James, Jia Shen, Xinli Zhang, Greg Asatrian, Raghav Goyal, Jin H Kwak, Lin Jiang, Benjamin Bengs, Cymbeline T Culiat, A Simon Turner, Howard B Seim Iii, Benjamin M Wu, Karen Lyons, John S Adams, Kang Ting, Chia Soo
NELL-1 is a secreted, osteoinductive protein whose expression rheostatically controls skeletal ossification. Overexpression of NELL-1 results in craniosynostosis in humans and mice, whereas lack of Nell-1 expression is associated with skeletal undermineralization. Here we show that Nell-1-haploinsufficient mice have normal skeletal development but undergo age-related osteoporosis, characterized by a reduction in osteoblast:osteoclast (OB:OC) ratio and increased bone fragility. Recombinant NELL-1 binds to integrin β1 and consequently induces Wnt/β-catenin signalling, associated with increased OB differentiation and inhibition of OC-directed bone resorption...
2015: Nature Communications
https://www.readbyqxmd.com/read/25913252/pharmacokinetics-and-osteogenic-potential-of-pegylated-nell-1-in-vivo-after-systemic-administration
#20
Jin Hee Kwak, Yulong Zhang, Juyoung Park, Eric Chen, Jia Shen, Chirag Chawan, Justine Tanjaya, Soonchul Lee, Xinli Zhang, Benjamin M Wu, Kang Ting, Chia Soo
Osteoporosis is a skeletal disorder attributable to an imbalance in osteoblast and osteoclast activity. NELL-1, a secretory protein that promotes osteogenesis while suppressing osteoclastic activity, holds potential as an osteoporosis therapy. Recently, we demonstrated that PEGylation of NELL-1 significantly improves its thermostability while preserving its bioactivity in vitro. However, the effect of PEGylation on the pharmacokinetics and osteogenic potential of NELL-1 in vivo have yet to be investigated...
July 2015: Biomaterials
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