Medium and method for proliferation and differentiation of alveolus organoids

Abstract

The invention discloses a medium and method for proliferation and differentiation of alveolus organoids. The method disclosed by the invention can reliably obtain the human alveolus organoids with relatively low cost and relatively high efficiency, and is beneficial to large-scale popularization and use of the alveolus organoids in the biomedical industry. The alveolus organoids related to the invention can remedy all the defects of a traditional alveolar in-vitro model at present, thereby meeting the four basic requirements of an alveolus disease model: (1) the alveolus organoids have the capabilities of sustained proliferation and sustained differentiation; (2) a complete tissue structure (monolayer polarized cystic epithelium) and normal physiological functions (for example secretion ofan alveolus surfactant, an alveolus innate immune process and the like) of alveoli in vivo can be retained or reproduced; (3) the alveolus organoids have good operability, and can be repeated cryopreserved, resuscitated and passaged like a cell line; and (4) the alveolus organoids come from human tissue and reflect individual differences.

Description

technical field [0001] The invention relates to the field of biotechnology, in particular to a culture medium and method for proliferation and differentiation of alveolar organoids. Background technique [0002] As the basic structural and functional unit of lung parenchyma, alveoli are the target tissues of various infectious diseases of the lower respiratory tract (such as SARS-Cov-2), and also participate in the occurrence and development of various non-infectious diseases of the respiratory system (such as pulmonary fibrosis chronic pulmonary obstruction, emphysema, bronchioloalveolar carcinoma). Alveolar organoids derived from human tissue can be used as research models of the above diseases. [0003] However, current traditional disease models such as primary alveolar epithelial cells (Yoko Ito et.al., IL-13 inducesperiostin and eotaxin expression in human primary alveolar epithelial cells: Comparison with paired airway epithelial cells, PLOS ONE, April 19, 2018. http...

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Problems solved by technology

[0003] However, current traditional disease models such as primary alveolar epithelial cells (Yoko Ito et.al., IL-13 inducesperiostin and eotaxin expression in human primary alveolar epithelial cells: Comparison with paired airway epithelial cells, PLOS ONE, April 19, 2018. https: / / doi.org / 10.1371 / journal.pone.0196256) and animal models (Thomas F.Rogerset.al., Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model, Science, 21Aug 2020: Vol .369, Issue 6506, pp.956-963, DOI: 10.1126 / science.abc7520) have major flaws, hindering the development of precision medicine

The traditional alveolar epithelial primary cell model has the following disadvantages: 1. Lack of self-proliferation and renewal ability, even with the support of trophoblast cells, multiple passages cannot be performed; 2. Cannot reflect individual differences; 3. Phenotype is easy to lose , that is, it is difficult to maintain the normal physiological function and structure of the alveoli in the body

Traditional animal models of lung diseases have the following disadvantages: 1. The cost of raising animals is high (such as humanized mouse models, primate models, etc.); 2. The pathogenesis of animal lung diseases, especially infectious diseases, is different from that of humans. There are large differences; 3. It cannot reflect the individual differences of human diseases; 4. Animal welfare issues

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