增加肾脏疾病研究的维度

写的:

Pernille Laerkegaard Hansen

澳门葡京网赌游戏生物科学肾部执行董事兼主管

米格尔·卡拉塞多·奥尔蒂斯

澳门葡京网赌游戏(AstraZeneca)早期CVRM生物科学肾部高级科学家

凯文Woollard

澳门葡京网赌游戏生物科学肾部高级主管

Kidneys have a complex structure which is critical to their function and this involves the cooperation of many different cell types. Studying single types of kidney cells grown in the lab has helped to advance our understanding of kidney health but we also need more advanced models to deepen our understanding of kidney function and to develop new medicines with greater potential to change the lives of people living with 肾脏疾病 – and this is where kidney organoids can help.

The purpose of our kidneys is to filter waste and excess water out of the blood so that it can be excreted as urine. The kidneys use pressure to first force most of the liquid and chemicals out of the blood and then selectively reabsorb anything that isn’t waste, 让它回到血液里.

世界上超过10%的人1 受…影响 肾脏疾病 它每年造成超过一百万人死亡,2 使其成为全球十大死因之一.3 肾脏疾病的原因可能是遗传的, 因为糖尿病的影响, 肾脏的高血压或炎症.2,4 某些药物的副作用也会对肾脏造成损害.5

什么是类肾器官?

肾脏生物学的研究方法多种多样,包括患者观察、动物模型和 在体外 模型基于实验室中培养的分离细胞群. Naturally there is only so much we can learn about the biology of 肾脏疾病 from patients and we know that different types of cells behave differently when we study them together in combination. Work with animals has also contributed to many discoveries but they are not always an accurate reflection of human health and disease.



 

Choosing the right research models is vital to developing our understanding of 肾脏疾病s and following the science to new therapies. 澳门葡京赌博游戏最近为国际肾脏病学会的发展做出了贡献 指导 关于模型在临床前研究中的应用. The 指导 includes 25 key recommendations including encouraging the consistent use of clinically relevant models, 适当时考虑类器官和其他创新模式系统, 考虑到性别等特征对临床前结果的影响.

 



Growing cells in the lab provides a better way to study human disease using human cells but it is still limited. 通常, it is only possible to study one type of cell at a time and the cells aren’t arranged or able to communicate in the way that they would inside the kidney. 直到最近, the complexity of the kidneys has made it impossible to grow lab-based models that can be used to study how the kidneys work.

A particular challenge has been a type of cells called podocytes that play a critical role in separating waste from the blood. 足细胞经常在肾脏疾病中受伤,使其成为研究的重点. Reproducing these functions when podocytes are grown in isolation is a challenge and this makes it difficult to study them using established cell culture methods.6


请听米格尔·卡拉塞多·奥尔蒂斯的报道, 为什么澳门葡京赌博游戏在研究中使用肾类器官


也被称为“迷你肾脏”, kidney organoids can teach us much more about kidney function and they can be made using populations of human cells so they provide a better tool for studying disease. 除了名字, 类器官并不是微型器官, 但通常看起来像三维中空的细胞球. They can be grown from just a few stem cells and include multiple different types of cells – including podocytes – which means they can behave much more like real kidneys.

With organoids we can better understand the interactions between different types of cells and explore how they work together within the kidney to carry out their essential functions. 多亏了 基因编辑技术,比如CRISPR, 使用携带不同遗传标记的细胞制造类器官也是可能的.7,8 This makes them an excellent way to understand the role of certain genes in causing disease and to investigate potential medicines for treating them.


The complexity of the kidney means it has been virtually impossible to create sophisticated models that duplicate the behaviour of the human kidney… Kidney organoids are miniature models derived from stem cells that closely mimic how the cells behave in the body.

米格尔·卡拉塞多·奥尔蒂斯 高级科学家,生物科学肾,澳门葡京赌博游戏R&D、澳门葡京网赌游戏

特别是, we have used these technologies to create kidney organoids to study podocyte function and investigate potential podocyte-targeting treatments.7 We have also published work describing the creation of organoids that mimic the cyst growth observed in patients with autosomal dominant polycystic 肾脏疾病, 肾脏疾病最常见的遗传原因.8 These models are supporting our work on pre-clinical target validation and advanced drug development for renal diseases.

利用肾类器官开发治疗肾病的药物

Organoids represent an exciting way to study the effects of novel treatments on aspects of human biology. 虽然他们无法在人体内完全复制这种情况, they offer much richer insights into how treatments could affect their target organ and can be used to explore how those responses could be altered by unique aspects of a patient’s biology.

像这样, organoids provide a vital tool in helping to bridge the gap between animal models and early-stage clinical trials and are helping us to develop a deeper understanding of the efficacy, 新疗法的风险和益处. 结果是, 可以更快地开发出安全有效的治疗方法, 最终使澳门葡京赌博游戏能够为患者提供更多改变生活的药物.




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参考文献

1. Bikbov B等. 全球, 区域, 以及慢性肾病的国家负担, 1990-2017: 2017年全球疾病负担研究的系统分析. 《澳门葡京网赌游戏》 (2020) 395(10225):709–33. DOI: 10.1016/S0140-6736(20)30045-3

2. 王,H.; Naghavi, M.; Allen C. 等. 全球, 区域, 国民平均寿命, 全因死亡率, 以及249种死因的特定死因死亡率, 1980-2015: 2015年全球疾病负担研究的系统分析 《澳门葡京网赌游戏》 (2016) 388, 10053, p1459-1544, DOI: 10.1016/S0140-6736(16)31012-1

3. 世界卫生组织,十大死亡原因简报,http://www.谁.int/news-room/fact-sheets/detail/the-top-10-causes-of-death (posted 9 Dec 2020; accessed Jan 2023)

4. 美国国立卫生研究院糖尿病、消化和肾脏疾病研究所, 什么是慢性肾病, http://www.的趋势.国家卫生研究院.gov/health-information/kidney-disease/chronic-kidney-disease-ckd/what-is-chronic-kidney-disease (accessed Feb 2023)

5. 约翰霍普金斯医学院,终末期肾病,http://www.hopkinsmedicine.http://www.health/conditions-anddiseases /终末期肾衰竭(2023年2月访问)

6. Hagmann H, Brinkkoetter PT. 足细胞生物学研究的实验模型:肾小球研究工具箱的盘点. 前面Pediatr. 2018年7月13日;6:193. DOI: 10.3389 / fp.2018.00193.

7. Boreström C, jononebring A,郭J 等. A CRISP(e)R view on kidney organoids allows generation of an induced pluripotent stem cell-derived kidney model for drug discovery. 肾脏Int. 2018年12月,94 (6):1099 - 1110. doi: 10.1016/j.号.2018.05.003.

8. shshamshirgaran Y, jononebring A, Svensson A 等. cas9诱导的hiPSC肾模型的快速靶标验证. Sci代表. 2021 Aug 16;11(1):16532. doi: 10.1038/s41598-021-95986-5.


Veeva ID: Z4-53246
筹备日期:2023年3月