神经系统疾病研究的新兴工具：脑类器官

前  言

大脑复杂的细胞组成和特定的结构，使得体外建模难度极大。近年来大脑类器官概括了大脑发育的许多关键特征，激发全-球神经学领域相关科研人员的兴趣，研究成果不断的发表于高分期刊，将脑类器官用于各种生理和病理研究。细胞因子作为类器官培养基中的添加试剂，可以引导细胞按特定器官谱系进行分化。为助力脑类器官的培养与分化，义翘神州可提供人EGF、FGF2、NOG、BMP4等一系列脑类器官培养相关产品。

01 脑类器官研究新进展

目前大多数脑部模型主要是人类死后脑组织、非人灵长类动物组织或者体外2D细胞。由于资源限制和动物模型的物种差异性等原因，使脑类器官成为潜在研究脑部生理和病理的模型。脑类器官主要源自胚胎干细胞（ESC）或者诱导性多能干细胞（iPSC）。对于体外神经生物学和神经发育障碍的疾病的研究，也会用到不同部位的脑类器官，比如前脑、中脑、海马脑类器官等。目前使用脑类器官模型涉及到阿尔茨海默症、帕金森病、自闭症、精神分裂等，甚至包括渐冻症、结节性硬化症等罕见病。

ASD, autism spectrum disorders; POMC, pro-opiomelanocortin.

（源自：https://doi.org/10.1002/bies.201900011）

02细胞因子在脑类器官中的应用

细胞因子在类器官培养过程中发挥重要作用。在多能干细胞（PSC）培养中加入了FGF2构建3D脑类器官模型。对于不同部位的脑类器官的培养，会加入不同的细胞因子，比如对于用于研究脊髓小脑共济失调疾病的小脑类器官培养中，会加入FGF2、FGF19、SDF1等细胞因子。

BDNF, brain‐derived neurotrophic factor; BMP, bone morphogenetic protein; cAMP, cyclic adenosine monophosphate; EGF, epidermal growth factor; FBS, fetal bovine serum; FGF, fibroblast growth factor; GDNF, glial cell‐derived neurotrophic factor. （源自：https://doi.org/10.1002/bies.201900011）

✦义翘神州细胞因子产品数据

Human FGF2 Protein, Cat: GMP-10014-HNAE 

高纯度：

≥ 95 % as determined by SDS-PAGE.

结合活性

Cell proliferation assay using Balb/C 3T3 mouse embryonic fibroblasts. The specific activity is >1,000 IU/μg.

Human Noggin Protein, Cat: 10267-HNAH

高纯度：

≥95% as determined by SDS-PAGE. ≥95% as determined by SEC-HPLC.

高批间一致性

Inhibit BMP4-induced alkaline phosphatase production by MC3T3E1 mouse preosteoblast cells.

☆：SDS-PAGE & SEC-HPLC

【参考文献】

1. Antoine Verger et al. FDA Approval of Lecanemab: The Real Start of Widespread Amyloid PET Use? — The EANM Neuroimaging Committee Perspective. European Journal of Nuclear Medicine and Molecular Imaging, 2023. https://doi.org/10.1007/s00259-023-06177-5.

2. Yujung Chang et al. Modelling Neurodegenerative Diseases with 3D Brain Organoids. Biological Reviews, 2020. https://doi.org/10.1111/brv.12626.

3. Jihoon Kim, Bon-Kyoung Koo, and Juergen A. Knoblich, Human Organoids: Model Systems for Human Biology and Medicine, Nature Reviews Molecular Cell Biology, 2020. https://doi.org/10.1038/s41580-020-0259-3.

4. Guini Song et al. The Application of Brain Organoid Technology in Stroke Research: Challenges and Prospects. Frontiers in Cellular Neuroscience, 2021. https://www.frontiersin.org/articles/10.3389/fncel.2021.646921.

5. Jay Gopalakrishnan. The Emergence of Stem Cell-Based Brain Organoids: Trends and Challenges. BioEssays, 2019. https://doi.org/10.1002/bies.201900011.

6. Madeline A. Lancaster and Juergen A. Knoblich. Generation of Cerebral Organoids from Human Pluripotent Stem Cells. Nature Protocols, 2014. https://doi.org/10.1038/nprot.2014.158.

7. Sebastian, R., et al. Schizophrenia-associated NRXN1 deletions induce developmental-timing- and cell-type-specific vulnerabilities in human brain organoids. Nat Commun, 2023. https://doi.org/10.1038/s41467-023-39420-6

8. Jimena Andersen, et al. Generation of Functional Human 3D Cortico-Motor Assembloids. Cell, 2020, doi:10.1016/j.cell.2020.11.017.

9. Yueqi Wang, et al. Modeling human telencephalic development and autism-associated SHANK3 deficiency using organoids generated from single neural rosettes. Nature Communications, 2022. https://doi.org/10.1038/s41467-022-33364-z

10. Fleck, J.S., et al. Inferring and perturbing cell fate regulomes in human brain organoids. Nature, 2022. https://doi.org/10.1038/s41586-022-05279-8

11. Oliver L. Eichmüller, et al. Amplification of human interneuron progenitors promotes brain tumors and neurological defects. Science, 2022. Doi: 10.1126/science.abf5546