본문 바로가기
KERD
논문KCI 등재

Blood-brain barrier-on-a-chip for brain disease modeling and drug testing

조승우|Baofang Cui
생화학분자생물학회 (Korean Society Of Biochemistry And Molecular Biology)|2022.05|BMB Reports|제55권 제5호|pp. 213-219

2

조회

0

다운로드

1

인용

0

참고문헌

키워드

Blood-brain barrierIn vitro modelingNeurological diseasesOrgan-on-a-chip
주제분류화학

초록

The blood-brain barrier (BBB) is an interface between cerebral blood and the brain parenchyma. As a gate keeper, BBB regulates passage of nutrients and exogeneous compounds. Owing to this highly selective barrier, many drugs targeting brain diseases are not likely to pass through the BBB. Thus, a large amount of time and cost have been paid for the development of BBB targeted therapeutics. However, many drugs validated in in vitro models and animal models have failed in clinical trials primarily due to the lack of an appropriate BBB model. Human BBB has a unique cellular architecture. Different physiologies between human and animal BBB hinder the prediction of drug responses. Therefore, a more physiologically relevant alternative BBB model needs to be developed. In this review, we summarize major features of human BBB and current BBB models and describe organ-on-chip models for BBB modeling and their applications in neurological complications.

Abstract

The blood-brain barrier (BBB) is an interface between cerebral blood and the brain parenchyma. As a gate keeper, BBB regulates passage of nutrients and exogeneous compounds. Owing to this highly selective barrier, many drugs targeting brain diseases are not likely to pass through the BBB. Thus, a large amount of time and cost have been paid for the development of BBB targeted therapeutics. However, many drugs validated in in vitro models and animal models have failed in clinical trials primarily due to the lack of an appropriate BBB model. Human BBB has a unique cellular architecture. Different physiologies between human and animal BBB hinder the prediction of drug responses. Therefore, a more physiologically relevant alternative BBB model needs to be developed. In this review, we summarize major features of human BBB and current BBB models and describe organ-on-chip models for BBB modeling and their applications in neurological complications.

참고문헌 (64)

  1. Abbott NJ, "Structure and function of the blood-brain barrier", Neurobiol Dis, 37, pp.13~25 (2010)
  2. Obermeier B, "Development, maintenance and disruption of the bloodbrain barrier", Nat Med, 19, pp.1584~1596 (2013)
  3. Abbott NJ, "Astrocyteendothelial interactions at the blood-brain barrier", Nat Rev Neurosci, 7, pp.41~53 (2006)
  4. Huber JD, "Molecular physiology and pathophysiology of tight junctions in the blood-brain barrier", Trends Neurosci, 24, pp.719~725 (2001)
  5. Abbott NJ, "Blood-brain barrier structure and function and the challenges for CNS drug delivery", J Inherit Metab Dis, 36, pp.437~449 (2013)
  6. Schinkel AH, "P-Glycoprotein, a gatekeeper in the blood-brain barrier", Adv Drug Deliv Rev, 36, pp.179~194 (1999)
  7. De Bock M, "Into rather unexplored terrain-transcellular transport across the blood-brain barrier", Glia, 64, pp.1097~1123 (2016)
  8. Pardridge WM, "The blood-brain barrier : bottleneck in brain drug development", NeuroRx, 2, pp.3~14 (2005)
  9. Banks WA, "From blood-brain barrier to blood-brain interface : new opportunities for CNS drug delivery", Nat Rev Drug Discov, 15, pp.275~292 (2016)
  10. Geldenhuys WJ, "Novel models for assessing blood-brain barrier drug permeation", Expert Opin Drug Metab Toxicol, 8, pp.647~653 (2012)
  11. Hajal C, "Biology and models of the blood-brain barrier", Annu Rev Biomed Eng, 23, pp.359~384 (2021)
  12. Van Norman GA, "Limitations of animal studies for predicting toxicity in clinical trials : is it time to rethink our current approach?", JACC Basic Transl Sci, 4, pp.845~854 (2019)
  13. Dawson TM, "Animal models of neurodegenerative diseases", Nat Neurosci, 21, pp.1370~1379 (2018)
  14. Akhtar A, "The flaws and human harms of animal experimentation", Camb Q Healthc Ethics, 24, pp.407~419 (2015)
  15. Bowman PD, "Brain microvessel endothelial cells in tissue culture : a model for study of blood-brain barrier permeability", Ann Neurol, 14, pp.396~402 (1983)
  16. Rauh J, "Development of an in vitro cell culture system to mimic the blood-brain barrier", Prog Brain Res, 91, pp.117~121 (1992)
  17. Stone NL, "A novel transwell blood brain barrier model using primary human cells", Front Cell Neurosci, 13, pp.230~ (2019)
  18. Srinivasan B, "TEER measurement techniques for in vitro barrier model systems", J Lab Autom, 20, pp.107~126 (2015)
  19. Clevers H, "Modeling development and disease with organoids", Cell, 165, pp.1586~1597 (2016)
  20. Pham MT, "Generation of human vascularized brain organoids", Neuroreport, 29, pp.588~593 (2018)
  21. Qian X, "Brain organoids:advances, applications and challenges", Development, 146, pp.dev166074~ (2019)
  22. Shi Y, "Vascularized human cortical organoids(vOrganoids)model cortical development in vivo", PLoS Biol, 18, pp.e3000705~ (2020)
  23. Cakir B, "Engineering of human brain organoids with a functional vascular-like system", Nat Methods, 16, pp.1169~1175 (2019)
  24. Mansour AA, "An in vivo model of functional and vascularized human brain organoids", Nat Biotechnol, 36, pp.432~441 (2018)
  25. Wang X, "Advances on fluid shear stress regulating blood-brain barrier", Microvasc Res, 128, pp.103930~ (2020)
  26. van der Meer AD, "Analyzing shear stress-induced alignment of actin filaments in endothelial cells with a microfluidic assay", Biomicrofluidics, 4, pp.11103~ (2010)
  27. Xu H, "A dynamic in vivo-like organotypic blood-brain barrier model to probe metastatic brain tumors", Sci Rep, 6, pp.36670~ (2016)
  28. Wang YI, "Microfluidic blood-brain barrier model provides in vivo-like barrier properties for drug permeability screening", Biotechnol Bioeng, 114, pp.184~194 (2017)
  29. Bhatia SN, "Microfluidic organs-onchips", Nat Biotechnol, 32, pp.760~772 (2014)
  30. Duffy DC, "Rapid prototyping of microfluidic systems in poly(dimethylsiloxane)", Anal Chem, 70, pp.4974~4984 (1998)
  31. Xia Y, "Soft lithography", Angew Chem Int Ed Engl, 37, pp.550~575 (1998)
  32. Viravaidya K, "Development of a microscale cell culture analog to probe naphthalene toxicity", Biotechnol Prog, 20, pp.316~323 (2004)
  33. Sin A, "The design and fabrication of three-chamber microscale cell culture analog devices with integrated dissolved oxygen sensors", Biotechnol Prog, 20, pp.338~345 (2004)
  34. Huh D, "Reconstituting organ-level lung functions on a chip", Science, 328, pp.1662~1668 (2010)
  35. Zhang B, "Advances in organ-on-a-chip engineering", Nat Rev Mater, 3, pp.257~278 (2018)
  36. Zhang B, "Organ-on-a-chip devices advance to market", Lab Chip, 17, pp.2395~2420 (2017)
  37. Ma C, "Organ-on-a-chip : a new paradigm for drug development", Trends Pharmacol Sci, 42, pp.119~133 (2021)
  38. Reardon S, "‘Organs-on-chips’ go mainstream", Nature, 523, pp.266~ (2015)
  39. Park TE, "Hypoxiaenhanced blood-brain barrier chip recapitulates human barrier function and shuttling of drugs and antibodies", Nat Commun, 10, pp.2621~ (2019)
  40. Seo S, "Triculture model of in vitro BBB and its application to study BBB-associated chemosensitivity and drug delivery in glioblastoma", Adv Funct Mater, 32, pp.2106860~ (2021)
  41. Bang S, "A low permeability microfluidic blood-brain barrier platform with direct contact between perfusable vascular network and astrocytes", Sci Rep, 7, pp.8083~ (2017)
  42. Urich E, "Multicellular self-assembled spheroidal model of the blood brain barrier", Sci Rep, 3, pp.1500~ (2013)
  43. Cho CF, "Blood-brainbarrier spheroids as an in vitro screening platform for brain-penetrating agents", Nat Commun, 8, pp.15623~ (2017)
  44. Eilenberger C, "A microfluidic multisize spheroid array for multiparametric screening of anticancer drugs and blood-brain barrier transport properties", Adv Sci(Weinh), 8, pp.e2004856~ (2021)
  45. Rosenberg GA, "Neurological diseases in relation to the blood-brain barrier", J Cereb Blood Flow Metab, 32, pp.1139~1151 (2012)
  46. Schoknecht K, "Blood-brain barrier dysfunction in brain diseases : clinical experience", Epilepsia, 53(Suppl 6), pp.7~13 (2012)
  47. Daneman R, "The blood-brain barrier in health and disease", Ann Neurol, 72, pp.648~672 (2012)
  48. Sweeney MD, "Blood-brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders", Nat Rev Neurol, 14, pp.133~150 (2018)
  49. Yoon JK, "Advanced human BBB-on-a-chip : a new platform for Alzheimer’s disease studies", Adv Healthc Mater, 10, pp.e2002285~ (2021)
  50. Drummond E, "Alzheimer’s disease : experimental models and reality", Acta Neuropathol, 133, pp.155~175 (2017)
  51. Golaszewska A, "Bridging the gap between Alzheimer’s disease and Alzheimer’s-like diseases in animals", Int J Mol Sci, 20, pp.1664~ (2019)
  52. Cummings J, "The"rights"of precision drug development for Alzheimer’s disease", Alzheimers Res Ther, 11, pp.76~ (2019)
  53. Shin Y, "Blood-brain barrier dysfunction in a 3D in vitro model of Alzheimer’s disease", Adv Sci(Weinh), 6, pp.1900962~ (2019)
  54. Yang C, "Neuroinflammatory mechanisms of blood-brain barrier damage in ischemic stroke", Am J Physiol Cell Physiol, 316, pp.C135~ (2019)
  55. Wang Y, "Obtaining human ischemic stroke gene expression biomarkers from animal models : a cross-species validation study", Sci Rep, 6, pp.29693~ (2016)
  56. Xiong Y, "Animal models of traumatic brain injury", Nat Rev Neurosci, 14, pp.128~142 (2013)
  57. Lyu Z, "A neurovascular-uniton-a-chip for the evaluation of the restorative potential of stem cell therapies for ischaemic stroke", Nat Biomed Eng, 5, pp.847~863 (2021)
  58. Chaudhuri JD, "Blood brain barrier and infection", Med Sci Monit, 6, pp.1213~1222 (2000)
  59. Kim J, "Fungal brain infection modelled in a human-neurovascular-unit-on-a-chip with a functional blood-brain barrier", Nat Biomed Eng, 5, pp.830~846 (2021)
  60. Buzhdygan TP, "The SARS-CoV-2 spike protein alters barrier function in 2D static and 3D microfluidic in-vitro models of the human blood-brain barrier", Neurobiol Dis, 146, pp.105131~ (2020)
  61. Kim Y, "The role of the microenvironment in tumor growth and invasion", Prog Biophys Mol Biol, 106, pp.353~379 (2011)
  62. Kim HN, "Microphysiological systems as enabling tools for modeling complexity in the tumor microenvironment and accelerating cancer drug development", Adv Funct Mater, 29, pp.1807553~ (2019)
  63. Pardridge WM, "Blood-brain barrier delivery", Drug Discov Today, 12, pp.54~61 (2007)
  64. Ahn SI, "Microengineered human blood-brain barrier platform for understanding nanoparticle transport mechanisms", Nat Commun, 11, pp.175~ (2020)

관련 논문AI추천

A review on biomimetic models based on microfluidic devices for drug research우승훈, Hwee Hyon Seo대한의학레이저학회 · Medical Lasers2024 · 제13권 제1호소의 뇌 미세혈관 내피세포를 이용한 생체외 혈액뇌관문 모델의 확립김경용, 김기정, 김대중, 김대진, 김성수, 방승규, 손동섭, 이원복, 이희상, 임인자대한체질인류학회 · 해부·생물인류학2003 · 제16권 제4호Human Brain Organoids: Development and ApplicationsFeng Jiang, Hongxi Wu, Jibing Chen, Qinglian Huang, Ruting Wang, Yiyang Liu한국미생물·생명공학회 · Journal of Microbiology and Biotechnology2025 · 제35권 Microphysiological Engineering of Immune Responses in Intestinal InflammationHyun Jung Kim, Soyoun Min, Woojung Shin, Yoko M. Ambrosini대한면역학회 · Immune Network2020 · 제20권 제2호Arterial Spin Labelling-Based Blood-Brain Barrier Assessment and Its ApplicationsAlishba Sadiq, Yiran Li, Ze Wang대한자기공명의과학회 · Investigative Magnetic Resonance Imaging2022 · 제26권 제4호The blood cerebrospinal fluid barrier orchestrates immunosurveillance, immunoprotection, and immunopathology in the central nervous system배재성, 진희경, AYUB MARIA생화학분자생물학회 · BMB Reports2021 · 제54권 제4호

이 간행물의 다른 논문 (6건)

New therapeutic approach with extracellular vesicles from stem cells for interstitial cystitis/bladder pain syndromeSoobin Lee, 김아람, 조쌍구, 송권우, 아브달아메드pp. 205-212Hepatitis B virus X protein promotes epithelial-mesenchymal transition of hepatocellular carcinoma cells by regulating SOCS1Jinchul Kim, Jeong Keun Ahn, Mi-jee Kim, Ju Hyeon Lee, Ji Ae Kim, Inho Kangpp. 220-225Endoplasmin regulates differentiation of tonsil-derived mesenchymal stem cells into chondrocytes through ERK signalingDong-Seok Park, Gang-Ho Yoon, Kyuhee Kim, Sun-Cheol Choipp. 226-231RNF152 negatively regulates Wnt/β-catenin signaling in Xenopus embryos박동석, Sun-Cheol Choi, Kyuhee Kim, Gang-Ho Yoonpp. 232-237Autistic-like social deficits in hippocampal MeCP2 knockdown rat models are rescued by ketamineHyeon Son, Huiju Lee, Do Gyeong Kim, Jee Young Seo, Seung Yeon Ko, Miyeon Choi, 정희경pp. 238-243
원문 보기