Organoid—Improve Disease Research and Drug Development

Organoids, 3D "micro-organ models" that are prepared from different types of stem cells through self-organization, can simulate the structure and function of native organs. Organoids represent an innovative technology that covers the physiological processes of the entire organism, having a closer physiological cell composition and behavior, a more stable genome, and is more suitable for biological transfection and high throughput screening. Compared with animal models, organoid models are easier to operate and can also be used to study the mechanisms of disease occurrence and development.

The preparation of organoids involves somatic cells, adult stem cells (including progenitor cells), or pluripotent stem cells. In 2009, the intestinal organ simulation technology was the first breakthrough that adult intestinal stem cells can proliferate and spontaneously organize in vitro. In addition to adult stem cells, pluripotent stem cells (including induced stem cells and embryonic stem cells) can also be utilized to prepare organoids based on their self-renewal and differentiation capabilities.

Applications

* Disease modelr
Organoids help clarify the development, homeostasis, and pathogenesis of diseases, and provide possible approaches for the diagnosis and treatment of diseases. The limitations of animal models pushed the study of tumor patient specimens. Commonly used human tumor models are patient derived organoid (PDO) and patients derived xenografts (PDX). A PDO, derived from a patient's cancer cells, provides reliable insights into the accurate and effective detection of complex diseases, and therefore guides clinical decisions. PDX models can be engrafted into immunocompromised mice and humanized mice for preclinical testing studies. Taking the brain organoid as an example, it demonstrates the specific neurogenesis process of human beings and provides a valuable opportunity for studying human brain development.

* Drug screeningr
A variety of primary tumors such as colon cancer, prostate cancer, breast cancer, and pancreatic cancer have corresponding organoids that are important preclinical screening models to predict individual patients' reaction to treatment, and a means of linking tumor-related genomic data with tumor biology, providing a research foundation for drug screening and personalized therapeutics. E.g., in clinical trials, the tumor organoids of patients with metastatic gastrointestinal cancer can reproduce their response to anticancer drugs.

* Adverse drug reaction studiesr
Adverse drug reactions, especially organ toxicity, are the main cause of the failure of drug development and withdrawal after marketing. General cell screening and animal model screening often cannot accurately predict the occurrence of adverse reactions in the human body. Kidney and liver toxicity are the most commonly seen organ toxicity, and artificially prepared kidney and liver organoids can provide more accurate means for toxicity prediction. Kidney organoids were proven to demonstrate the nephrotoxicity caused by cisplatin and gentamicin.

* Gene therapy & cell therapyr
Transplantation of functional organoids (or cells from organoids) is conducted in tissue experiments such as colon, liver, pancreas, retina, and thyroid. However, more research is needed to evaluate the effectiveness and safety of these methods.

Organoids Biobankr
More and more laboratories and hospitals are collecting tumor organoids and corresponding healthy tissue organoids, and using appropriate cryopreservation and passage methods for large-scale preservation. In May 2018, the world's first cancer organoid biobank was published on Cell. Organoids are classified according to patient information, tissue sources, gene phenotypes, etc., providing public tumor research resource for evaluating the tumor killing effect of antitumor drugs and the toxic side effects of normal tissues.