A human 3D bone-sensory nerve co-culture model to investigate bone-derived pain
用于研究骨源性疼痛的人体 3D 骨感觉神经共培养模型
基本信息
- 批准号:NC/Y000951/1
- 负责人:
- 金额:$ 64.59万
- 依托单位:
- 依托单位国家:英国
- 项目类别:Research Grant
- 财政年份:2023
- 资助国家:英国
- 起止时间:2023 至 无数据
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
Background Bone-derived pain from conditions such as cancer metastasis, non-healing fracture, osteoporotic fracture, or osteoarthritis (OA) are notoriously hard to manage and prevalent, with an estimated 1.5 million bone cancer metastases, 22 million non-union factures, 8.9 million osteoporotic fractures and 530 million OA sufferers currently worldwide. Complex signalling exists between bone and nerves which couple pathology and pain in health and disease. Sensory nerve invasion and sensitisation are associated with bone diseases, and intrinsic to pain responses in animal models and human patients with osteoarthritis, fracture and bone metastasis. This project aims to (i) develop a humanised 3D bone-sensory nerve co-culture model, (ii) use the model to investigate mechanisms linking changes in bone structure to local pain sensation and (iii) test whether the model can screen 2 drugs known to prevent pain and influence bone structure.Investigating bone-nerve interactions is challenging due to the position of these nerves within mineralised bone. Currently, no human derived models of the sensory nerve-bone interface exist. Some models of bone pain have been produced that use nerves from the spine, called dorsal root ganglia (DRG) from animals and humans, but are technically challenging and not commonly adopted. Animal models are extensively used for the investigation of bone derived pain. In 2019, over 650 original research papers were published investigating bone derived pain in pathology using animal models, 4% of which were large animals including canines, with an average of 23 animals typically used per study, totalling over 14000 animals. A pharmaceutical company testing drugs for bone pain may use more than 1000 animals p.a. In a recent review on orthopaedic animal testing15, it was revealed that over a 9-year period, 40% of academic orthopaedic animal studies were never published and almost half of those published were never cited totalling nearly 10,000 animal lives with no justifiable impact on orthopaedic knowledge. Animal models of osteoarthritis use >10 animals per group to reveal effects on bone structure and pain. For example, in osteoarthritis research 132-198 mice or 360 rats would be used to test 1 drug. Our new bone-sensory nerve model will facilitate low-cost research to identify new molecular targets and pre-screening of drugs for pain. It will reduce early-stage preclinical research animal usage, and replace models currently used to identify and test new treatments to ease bone derived pain. We will promote the use of this model over animal testing through dissemination at national and International conferences and workshops (e.g. Orthopaedic Research Society Preclinical Models Section, British Orthopaedic Research Society, Osteoarthritis Research Society International), and by validation with drugs from our current collaborators in the pharmaceutical industry.
背景骨源性疼痛的条件,如癌症转移,不愈合的骨折,骨质疏松性骨折,或骨关节炎(OA)是众所周知的难以管理和普遍的,估计有150万骨癌转移,2200万骨不连骨折,890万骨质疏松性骨折和5.3亿OA患者目前在世界各地。复杂的信号传导存在于骨骼和神经之间,其耦合健康和疾病中的病理和疼痛。感觉神经侵袭和敏化与骨疾病相关,并且是骨关节炎、骨折和骨转移的动物模型和人类患者中疼痛反应的内在原因。该项目旨在(i)开发一个人源化的3D骨-感觉神经共培养模型,(ii)使用该模型研究骨结构变化与局部疼痛感觉之间的联系机制,(iii)测试该模型是否可以筛选2种已知的预防疼痛和影响骨结构的药物。由于这些神经在矿化骨中的位置,研究骨-神经相互作用具有挑战性。目前,不存在感觉神经-骨界面的人类衍生模型。已经产生了一些使用来自脊柱的神经的骨痛模型,这些神经被称为来自动物和人类的背根神经节(DRG),但是在技术上具有挑战性并且不被普遍采用。动物模型广泛用于骨源性疼痛的研究。2019年,发表了650多篇使用动物模型研究骨源性疼痛病理学的原创研究论文,其中4%是大型动物,包括犬,平均每次研究通常使用23只动物,总计超过14000只动物。一家制药公司测试骨痛药物可能每年使用1000多只动物。最近一项关于骨科动物试验的综述15显示,在9年的时间里,40%的骨科学术动物研究从未发表,其中近一半从未被引用,总计近10,000只动物的生命对骨科知识没有合理的影响。骨关节炎的动物模型每组使用>10只动物以揭示对骨结构和疼痛的影响。例如,在骨关节炎研究中,将使用132-198只小鼠或360只大鼠来测试1种药物。我们新的骨感觉神经模型将促进低成本研究,以确定新的分子靶点和预先筛选疼痛药物。它将减少早期临床前研究动物的使用,并取代目前用于识别和测试缓解骨源性疼痛的新疗法的模型。我们将通过在国家和国际会议和研讨会(例如骨科研究学会临床前模型部分,英国骨科研究学会,骨关节炎研究学会国际)上的传播,以及通过与我们目前在制药行业的合作者的药物进行验证,来促进该模型在动物试验中的使用。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Deborah Mason其他文献
Endovascular Thrombectomy Treatment Effect in Direct vs Transferred Patients With Large Ischemic Strokes: A Prespecified Analysis of the SELECT2 Trial.
血管内血栓切除术对直接与转移的大面积缺血性中风患者的治疗效果:SELECT2 试验的预先指定分析。
- DOI:
- 发表时间:
2024 - 期刊:
- 影响因子:29
- 作者:
A. Sarraj;Michael D Hill;M. S. Hussain;Michael G. Abraham;S. Ortega‐Gutierrez;Michael Chen;Scott E. Kasner;Leonid Churilov;D. Pujara;Hannah T Johns;Spiros Blackburn;S. Sundararajan;Yin C Hu;N. Herial;R. Budzik;William J Hicks;J. Arenillas;Jenny P. Tsai;Osman Kozak;D. Cordato;Ricardo A. Hanel;Teddy Y. Wu;P. Portela;Chirag D. Gandhi;F. Al;Laith N Maali;D. Gibson;N. Pérez de la Ossa;Joanna D. Schaafsma;Jordi Blasco;Navdeep Sangha;Steven Warach;T. Kleinig;Faris Shaker;C. Sitton;Thanh N Nguyen;J. Fifi;P. Jabbour;A. Furlan;M. Lansberg;G. Tsivgoulis;Cathy A Sila;Nicholas C Bambakidis;S. Davis;L. Wechsler;G. W. Albers;J. C. Grotta;Marc Ribó;Bruce C Campbell;A. Hassan;A. Sarraj;S. Sundararajan;Yin C Hu;Cathy Sila ;Anthony Furlan ;Amanda Opaskar ;Nicholas Bambakidis ;Abhishek Ray ;Jeffrey Sunshine ;Michael DeGeorgia;Wei Xiong;Rose Duncan ;Ali Fadhil ;John Hansen;Mohit Patel;Arunit S Chugh;Faisal Al‐Shaibi;Majed Alomar;Soheil El;Rami B Moussa;Dasul Jin;Katrina M Nayak;Yiyi Zhang;Nikhil S Modak;M. Jumah;Deng;Abdullah Alamoudi;D. Pujara;Spiros Blackburn;J. C. Grotta;C. Sitton;Mohammad H. Rahbar;Mark Dannenbaum ;Roy Riascos;Gary Spiegel ;Andrew Barreto ;Anjail Sharieff ;Joseph Cochran ;Arthur L. Day ;Nicole Gonzales ;Sujan Reddy ;Lauren Fournier ;Erica M Jones ;Pamela Zelini ;Haris Kamal ;Felix Guerra Castanon;Naveed Asim;Faris Shaker;M. Hessabi;A. Tahanan;Michael G. Abraham;Laith N Maali;Koji Ebersole ;Jorge Kawano ;Colleen Lechtenberg ;Sabreena Slavin ;Latih Maali ;Ernest Madarang ;Aparna Pendurthi ;Abid Qureshi ;Alan Reeves ;Lee Rosterman ;Yunxia Wang ;Tiffany Thu Barkley ;Husitha Vanguru ;Jeremy Paterson ;Carissa Walters ;Peyton Ackerman ;Ricardo A. Hanel;Amin Aghaebrahim;Eric Sauvageau ;Gina Munden ;M. S. Hussain;M. Abdulrazzak;Ken Uchino ;Irene Katzan ;Mei Lu ;Gabor Toth ;Andrew Russman ;Dolora Wisco ;Jayashree Sundararajan ;Andrew Buletko ;Mark Bain ;Nina Moore ;Alex Witek ;Marek Cierny ;Ashutosh Mahapatra ;Ghulum Kharal ;Denice Limbert ;Tina Resser ;Laura J Sweeney ;Michael Chen;Stephan Munich ;Richard Crowley ;Elizabeth McLaughlin ;Sarah Song ;Rebecca McWilliams ;Bartosz Jacher ;Steven Warach;Truman J. Milling ;Jefferson Miley ;Kent Ellington ;Aliaksandra Regan ;Jessica Erfan ;Manzure Mawla ;Lisa Davis ;Nathan Zuck ;R. Budzik;William J Hicks;Nirav Vora ;Peter Pema ;Abdulnasser Alhajeri ;Aaron Loochtan ;Vivek Rai ;Brian Katz ;Adam Koss ;N. Dedhia;Katy Groezinger ;Megan Heckathorn ;Heather Bartelt;Navdeep Sangha;Duy Le;Lei Feng;Kuo Chao;Pamela K Cheng ;Zahra A Ajani ;Catherine L Lui ;Ashima Sharma ;Osman Kozak;L. Mackenzie;H. Choe;Patricia Bussinger ;Ashley DePalmo ;A. Hassan;Wondwossen Tekle;Alexandros Georgiadis;Olive Sanchez ;Pualani Smith ;D. Gibson;Adam N Wallace;Tracy Mente;Margaret Wilson;S. Ortega‐Gutierrez;E. Samaniego;Colin Derdeyn ;Kathleen Dlouhy ;David Hasan ;Minako Hayakawa ;Enrique Leira ;Kaustubh Limaye ;Amir Shaban ;Hyung Sub Shim ;Malik Ghannam ;Cynthia Zeballos;Jason Maljaars;Prateeka Koul;Mohammad AlMajali;Heena Olalde ;Harika A Kekinagath;L. Elijovich;Adam Arthur ;Daniel Hoit ;Christopher Nickele ;Violiza Inoa ;Nitin Goyal ;Stephanie Wilson ;Kaushik Parsha ;Amanda Nolte ;N. Herial;P. Jabbour;Stavropoula Tjoumakaris ;Michael Reid Gooch ;Thana Theofanis ;Robert H. Rosenwasser ;Victoria Schunemann;Rizwan Tahir;Mohamed S Eldin ;Roland Jabre ;Jared Chen ;Nadirah Jones ;Scott E. Kasner;Brett L Cucchiara ;Steven Russell Messe ;Jens Witsch ;Donna George ;Christopher Favilla ;Qingyang Yuan ;Laura A Stein ;Paul Novello ;Aaron Rothstein ;Daniel Cristancho ;Kelly Sloane ;Kelley Humbert ;Jonah Zuflacht ;Arooshi Kumar ;Farhan Khan ;Michael Mullen ;Judy Dawod ;Jan;Brian Jankowitz ;Bryan Pukenas ;Omar Choudhri ;Preethi Ramchand ;Sahily Reyes;Gbambele Kone ;Nino Kvantaliani ;Michela Rosso ;Sydni Cole ;Ossama Khazaal ;Nichole Gallatti ;Jenny P. Tsai;Jiangyong Min ;Nabil Wees ;Amjad Abdallah ;Muhib A. Khan ;Nadeem Khan ;Asad Ahrar;P. Mazaris;Miller Malgorzata;Justin Singer;Ryan S. Groseclose;Beenish I. Sultan ;D. Sahlein;Krishna Amuluru ;John Scott ;Andrew DeNardo ;David Rosenbaum ;Kati Campbell ;Chirag D. Gandhi;Fawaz Al;Gurmeen Kaur ;J. Santarelli;Nicole Lemrick ;Heather Cero ;Kevin Clare ;Bridget Nolan ;Joanna D. Schaafsma;T. Stewart;A. Cayley;C. Jaigobin;Leanne Casaubon;Patrick Nicholson;R. Agid;Frank L Silver;A. Pikula;W. To;L. Crellin;Ashfaq Shuaib;Nina Sobreira;Bruce C Campbell;Bernard Yan;V. Yogendrakumar;F. Ng;P. J. Mitchell;R. J. Dowling;Steven Bush;Cameron Williams;N. Yassi;Davor Pavlin;J. Beharry;A. Balabanski;Angela dos Santos;A. Sharobeam;M. Valente;A. Park;J. Wong;A. McDonald;David Jackson;G. Sharma;Prodipta Guha;Birendra Rokaha;T. Kleinig;R. Scroop;C. Kurunawai;J. Mahadevan;R. Goh;R. Drew;D. Cordato;N. Manning;M. Parsons;A. McQuinn;J. Wenderoth;Andrew Cheung;A. McDougall;James Thomas;C. Cappelen;Christopher Blair;Leon Edwards;Justin Whitely;Jacob Helou;Megan Miller;Teddy Y. Wu;W. Collecutt;Frances Colgan;Martin Krauss;Andrew Laing;D. Wilson;John Fink;Campbell LeHeron;Deborah Mason;Rosemary Green ;Kathleen Bremner;Marc Ribó;A. Tomasello;Manuel Requena Ruiz;Marta Olivé Gadea;E. Sanjuan;Judith Cendrero;Jordi Blasco;A. Renú;L. San Román;Xabi Urra;Daniel Santana;Jose Maria Cabrera;L. Llull;A. López;Andrea Cabero;Elena Serrano;N. Pérez de la Ossa;María Hernández;Mónica Millán;M. Gomis;Alejandro Bustamante;L. Dorado;M. Gómez;S. Remollo;C. Castaño;M. Werner;Lucía Muñoz;Pere Cardona;H. Quesada;B. Lara;A. Paipa;Anna Nuñez;Víctor Cuba;Oscar Chirife;L. Aja;M. D. de Miquel;J. Arenillas;M. de Lera Alfonso;María Esther Ramos Araque;Ana Calleja;E. Cortijo;M. Martínez‐Galdámez;Miguel Schüller;Jorge Galván;Javier Reyes Muñoz;Gómez Beatriz Vicente;Marios;A. Brehm;Nirav Vora;N. Manning;Andrew Cheung;Amin Aghaebrahim;A. J. Paipa Merchán;D. Sahlein;Manuel Requena Ruiz;L. Elijovich;A. Arthur;Faisal Al‐Shaibi;E. Samaniego;K. Duncan;A. Opaskar;Abhishek Ray;Wei Xiong;J. Sunshine;Michael DeGeorgia;S. Tjoumakaris;Vitor Mendes Pereira - 通讯作者:
Vitor Mendes Pereira
Increased Large Vessel Occlusive Strokes After the Christchurch March 15, 2019, Terror Attack
2019 年 3 月 15 日基督城恐怖袭击后大型血管闭塞性中风增加
- DOI:
- 发表时间:
2020 - 期刊:
- 影响因子:9.9
- 作者:
Teddy Y. Wu;D. Myall;David Palmer;J. Beharry;Jen Yuh Lim;Deborah Mason;Jon Reimers;R. Duncan;James Weaver;W. Collecutt;P. Mouthaan;Anthony Lim;M. Hurrell;P. Barber;A. Ranta;J. Fink;C. Heron - 通讯作者:
C. Heron
36. Disability and MS in New Zealand
- DOI:
10.1016/j.jocn.2009.07.061 - 发表时间:
2009-11-01 - 期刊:
- 影响因子:
- 作者:
Deborah Mason;Glynnis Clarke;John Pearson;Bruce Taylor - 通讯作者:
Bruce Taylor
Osteoporosis screening in Australian community pharmacies: A mixed methods study.
澳大利亚社区药房的骨质疏松症筛查:一项混合方法研究。
- DOI:
10.1002/hpja.876 - 发表时间:
2024 - 期刊:
- 影响因子:1.9
- 作者:
Jonathan Phuong;Rebekah Moles;Deborah Mason;Christopher P. White;Jacqueline Center;SR. Carter - 通讯作者:
SR. Carter
Deborah Mason的其他文献
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