Abstract:Type 2 diabetes mellitus (T2DM) is a systematic multi-organ metabolic disease, which is characterized by the dynamic interplay among different organs. The increasing incidence of T2DM reflects an urgent need for the development of in vitro human-relevant models for disease study and drug therapy. Here, a new microfluidic multi-organoid system is developed that recapitulates the human liver-pancreatic islet axis in normal and disease states. The system contains two compartmentalized regions connected by a micro… Show more
“…In one impressive example of complex physiological mimicry, dynamic inter-organ hormonal coupling and the 28-day menstrual cycle were reconstituted in vitro by fluidically linking human organ chip models of uterus, cervix, fallopian tube and liver to a mouse ovary chip and recirculating the medium 25 . Coupled organ chip systems have also been used to model multi-organ regulation of insulin secretion 30 , 102 ; metastatic spread of cancer between different organs 103 ; targeted immune responses to organ-specific damage 104 ; and the toxic effects of environmental chemicals that required hepatic bioactivation 105 , including activation of germ cell toxins in linked liver and testis chips 31 .…”
Section: Clinical Mimicry In Organ Chipsmentioning
confidence: 99%
“…In addition, when the intestine chip was replaced by a bone marrow chip, predictions of cisplatin pharmacodynamics also matched previously reported patient data 35 . As these body-on-chip systems are modular, the chips can be linked either in series or in parallel, and the flow can be either unidirectional 13 , 30 , 34 , 35 , 102 , 103 , 105 , 111 , 112 or recirculated 25 , 27 , 28 , 31 , 32 , 104 , 106 – 110 , 113 . Fig.…”
Section: Clinical Mimicry In Organ Chipsmentioning
The failure of animal models to predict therapeutic responses in humans is a major problem that also brings into question their use for basic research. Organ-on-a-chip (organ chip) microfluidic devices lined with living cells cultured under fluid flow can recapitulate organ-level physiology and pathophysiology with high fidelity. Here, I review how single and multiple human organ chip systems have been used to model complex diseases and rare genetic disorders, to study host–microbiome interactions, to recapitulate whole-body inter-organ physiology and to reproduce human clinical responses to drugs, radiation, toxins and infectious pathogens. I also address the challenges that must be overcome for organ chips to be accepted by the pharmaceutical industry and regulatory agencies, as well as discuss recent advances in the field. It is evident that the use of human organ chips instead of animal models for drug development and as living avatars for personalized medicine is ever closer to realization.
“…In one impressive example of complex physiological mimicry, dynamic inter-organ hormonal coupling and the 28-day menstrual cycle were reconstituted in vitro by fluidically linking human organ chip models of uterus, cervix, fallopian tube and liver to a mouse ovary chip and recirculating the medium 25 . Coupled organ chip systems have also been used to model multi-organ regulation of insulin secretion 30 , 102 ; metastatic spread of cancer between different organs 103 ; targeted immune responses to organ-specific damage 104 ; and the toxic effects of environmental chemicals that required hepatic bioactivation 105 , including activation of germ cell toxins in linked liver and testis chips 31 .…”
Section: Clinical Mimicry In Organ Chipsmentioning
confidence: 99%
“…In addition, when the intestine chip was replaced by a bone marrow chip, predictions of cisplatin pharmacodynamics also matched previously reported patient data 35 . As these body-on-chip systems are modular, the chips can be linked either in series or in parallel, and the flow can be either unidirectional 13 , 30 , 34 , 35 , 102 , 103 , 105 , 111 , 112 or recirculated 25 , 27 , 28 , 31 , 32 , 104 , 106 – 110 , 113 . Fig.…”
Section: Clinical Mimicry In Organ Chipsmentioning
The failure of animal models to predict therapeutic responses in humans is a major problem that also brings into question their use for basic research. Organ-on-a-chip (organ chip) microfluidic devices lined with living cells cultured under fluid flow can recapitulate organ-level physiology and pathophysiology with high fidelity. Here, I review how single and multiple human organ chip systems have been used to model complex diseases and rare genetic disorders, to study host–microbiome interactions, to recapitulate whole-body inter-organ physiology and to reproduce human clinical responses to drugs, radiation, toxins and infectious pathogens. I also address the challenges that must be overcome for organ chips to be accepted by the pharmaceutical industry and regulatory agencies, as well as discuss recent advances in the field. It is evident that the use of human organ chips instead of animal models for drug development and as living avatars for personalized medicine is ever closer to realization.
“…As we recapitulate in the last section, the co-culture system of islets and other organs is an efficient disease modeling platform. In summary, most commonly used co-culture system to study the impact of organ crosstalk in type 2 DM including duct- and pancreatic islets-on-a-chip [ 63 ], liver- and pancreatic islets-on-a-chip [ 67 , 68 ]. Fat is one of the most important tissues in the development of diabetes.…”
Section: Chip For Drug Screeningmentioning
confidence: 99%
“…To reproduce the human liver-pancreatic islet dualorgan feedback platform in normal and diseased states, Qin et al [68] developed a new microfluidic Fig. 4 Pancreatic islets-on-a-chip for disease modeling.…”
Section: Chip For Diabetes-related Disease Modelingmentioning
Diabetes mellitus (DM) is a disease caused by dysfunction or disruption of pancreatic islets. The advent and development of microfluidic organoids-on-a-chip platforms have facilitated reproduce of complex and dynamic environment for tissue or organ development and complex disease processes. For the research and treatment of DM, the platforms have been widely used to investigate the physiology and pathophysiology of islets. In this review, we first highlight how pancreatic islet organoids-on-a-chip have improved the reproducibility of stem cell differentiation and organoid culture. We further discuss the efficiency of microfluidics in the functional evaluation of pancreatic islet organoids, such as single-islet-sensitivity detection, long-term real-time monitoring, and automatic glucose adjustment to provide relevant stimulation. Then, we present the applications of islet-on-a-chip technology in disease modeling, drug screening and cell replacement therapy. Finally, we summarize the development and challenges of islet-on-a-chip and discuss the prospects of future research.
Graphical Abstract
“…Some research groups developed a body-on-a-chip comprising the ADME organs but any was fully based on iPSCs. 143 To the other hand, there are examples of multi-OoC where the cells were fully generated from iPSCs 144 , 145 but these systems were not applied to drug screening.…”
The Organ-on-a-Chip (OoC) technology shows great potential to revolutionize the drugs development pipeline by mimicking the physiological environment and functions of human organs. The translational value of OoC is further enhanced when combined with patient-specific induced pluripotent stem cells (iPSCs) to develop more realistic disease models, paving the way for the development of a new generation of patient-on-a-chip devices. iPSCs differentiation capacity leads to invaluable improvements in personalized medicine. Moreover, the connection of single-OoC into multi-OoC or body-on-a-chip allows to investigate drug pharmacodynamic and pharmacokinetics through the study of multi-organs cross-talks. The need of a breakthrough thanks to this technology is particularly relevant within the field of neurodegenerative diseases, where the number of patients is increasing and the successful rate in drug discovery is worryingly low. In this review we discuss current iPSC-based OoC as drug screening models and their implication in development of new therapies for neurodegenerative disorders.
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