Translational research : the journal of laboratory and clinical medicine
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Review
Importance of Multiple Endocrine Cell Types in Islet Organoids for Type 1 Diabetes Treatment.
Almost 50 years ago, scientists developed the bi-hormonal abnormality hypothesis, stating that diabetes is not caused merely by the impaired insulin signaling. Instead, the presence of inappropriate level of glucagon is a prerequisite for the development of type 1 diabetes (T1D). It is widely understood that the hormones insulin and glucagon, secreted by healthy β and α cells respectively, operate in a negative feedback loop to maintain the body's blood sugar levels. ⋯ In this review, we describe the unique function of each pancreatic endocrine cell type and their interactions contributing to the maintenance of normoglycemia. Furthermore, we detail current sources of whole islets and techniques for their long-term expansion and culture. In addition, we highlight a vast potential of the pancreatic islet organoids for transplantation and diabetes research along with updated new approaches for successful transplantation using stem cell-derived islet organoids.
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Bacteria, fungi, viruses, and protozoa are known to infect and induce diseases in the human central nervous system (CNS). Modeling the mechanisms of interaction between pathogens and the CNS microenvironment is essential to understand their pathophysiology and develop new treatments. ⋯ Here in this review, we highlight several infectious diseases which have been tested in human brain organoids and compare similarities in response to these pathogens across different investigations. We also provide a brief overview of some recent advancements which can further enrich this model to develop new and better therapies to treat brain infections.
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The kidney is a vital organ that regulates the bodily fluid and electrolyte homeostasis via tailored urinary excretion. Kidney injuries that cause severe or progressive chronic kidney disease have driven the growing population of patients with end-stage kidney disease, leading to substantial patient morbidity and mortality. This irreversible kidney damage has also created a huge socioeconomical burden on the healthcare system, highlighting the need for novel translational research models for progressive kidney diseases. ⋯ By applying gene editing technology, organoid building blocks may be modified to minimize the process of immune rejection in kidney transplant recipients. In the foreseeable future, the universal kidney organoids derived from HLA-edited/deleted induced pluripotent stem cell (iPSC) lines may enable the supply of bioengineered organotypic kidney structures that are immune-compatible for the majority of the world population. Here, we summarize recent advances in kidney organoid research coupled with novel technologies such as organoids-on-chip and biofabrication of 3D kidney tissues providing convenient platforms for high-throughput drug screening, disease modelling, and therapeutic applications.
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Despite progress in prevention and treatment, colorectal cancer (CRC) remains the third most common malignancy worldwide and the second most common cause of cancer death in 2020. To evaluate various characteristics of human CRC, a variety of mouse models have been established. Transplant mouse models have distinct advantages in studying the clinical behavior and therapeutic progress of CRC. ⋯ These milestone events have allowed for great progress in tumor biology and the treatment of CRC. This article reviews the evolution of these events and points out their strengths and weaknesses as innovative and useful preclinical tools to study CRC progression and metastasis and to exploit novel treatment schedules by establishing a testing platform. This review article depicts the optimal transplanted CRC mouse models and emphasizes the significance of surgical models in the study of CRC behavior and treatment response.
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During the progression of diabetic kidney disease (DKD), renal lactate metabolism is rewired. The relationship between alterations in renal lactate metabolism and renal fibrosis in patients with diabetes has only been partially established due to a lack of biopsy tissues from patients with DKD and the intricate mechanism of lactate homeostasis. The role of lactate dehydrogenase A (LDHA)-mediated lactate generation in renal fibrosis and dysfunction in human and animal models of DKD was explored in this study. ⋯ We found that the pathogenesis of DKD is linked to hypoxia-mediated lactic acidosis, which leads to fibrosis and mitochondrial abnormalities. The pathogenic characteristics of DKD were significantly reduced when aerobic glycolysis or LDHA expression was inhibited. Further studies will aim to investigate whether local acidosis caused by renal LDHA might be exploited as a therapeutic target in patients with DKD.