Separated proliferative microglial cells, preparation method thereof and application of separated proliferative microglial cells in replacement of microglial cells

A technology of microglia and macrophages, applied in the field of microglia and their preparation, can solve the problems of weakening the proliferation ability of microglia and myeloid cells in the host CNS, and achieves omitting myeloablative treatment, Improve competitive advantage and reduce risk

CN114574440APending Publication Date: 2022-06-03SHENZHEN INST OF ADVANCED TECH
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Publication Date
2022-06-03

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Abstract

The invention relates to a separated proliferative microglial cell, a preparation method thereof and application of the separated proliferative microglial cell in microglial cell replacement. The preparation method comprises the following steps: giving a macrophage-colony factor 1 receptor inhibitor to other donors except a host, and stopping giving the macrophage-colony factor 1 receptor inhibitor, so as to obtain the separated proliferative microglial cells. And or overexpressing a macrophage-colony factor 1 receptor in the donor microglial cells, and obtaining proliferative microglial cells from the donor 3 days after stopping the administration of a macrophage-colony factor 1 receptor inhibitor. The invention also discloses an application of the separated proliferative microglial cells in improving the competitive advantage of the microglial cells entering the biological niche. The exogenous microglia provided by the invention can improve the competitive advantage of entering an ecological niche, so that the myelocleaning treatment intensity can be greatly reduced, the risk is further reduced, and the safety is improved.
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Description

Technical field

[0001] The present invention belongs to the field of biological drugs, specifically relates to an isolated relative endogenous microglia has a competitive advantage of microglia and preparation method thereof. Background

[0002] Microglia are important immune cells in the central nervous system (CNS), and microglia carrying genetic mutations are involved in the occurrence and development of a variety of neurodegenerative lesions. For example, 50% of the currently known genomic risk sites for Alzheimer's disease are expressed in microglia >. Therefore, replacing diseased microglia, or enhancing microglia function, has great clinical application prospects. Conventional gene therapy ideas cannot be used for microglia, mainly due to: 1. Commonly used non-integrative viral vectors (such as AAV) cannot infect microglia; 2. Integrative viral vectors (such as lentivirus) can infect microglia, but they can only affect the cells locally at the injection site, and cannot...

Examples

Embodiment 1

[0072] 1) Medullary cell proliferation in the central nervous system of wild-type mice with non-lethal dose irradiation and / or demineralizing drug busulfan, while macrophage colony factor 1 receptor inhibitors are used to remove endogenous microglia in the host central nervous system;

[0073] 2) Give other wild-type mouse donors other than wild-type mouse hosts with macrophage colony factor 1 receptor inhibitors, and obtain proliferative microglia from the donor on the 3-5th day after the cessation of macrophage colony factor 1 receptor inhibitors; And in step 1) the central nervous system of the treated host is inhibited by myeloid cells and microglia, more than 95% of the host microglia are eliminated with the drug, and within 24 to 48 hours after withdrawal, proliferative microglia are implanted;

[0074] 3) Give the host bone marrow cells or hematopoietic stem cells; Myeloid cells produced by said bone marrow cells or hematopoietic stem cells are able to be eliminated by his ...