Synthetic Biology Journal ›› 2024, Vol. 5 ›› Issue (4): 754-769.DOI: 10.12211/2096-8280.2023-102
• Invited Review • Previous Articles Next Articles
Yuan HONG1,2,3, Yan LIU1,4,5
Received:
2023-12-01
Revised:
2024-05-29
Online:
2024-09-19
Published:
2024-08-31
Contact:
Yan LIU
洪源1,2,3, 刘妍1,4,5
通讯作者:
刘妍
作者简介:
基金资助:
CLC Number:
Yuan HONG, Yan LIU. Research progress of brain organoids in regenerative medicine[J]. Synthetic Biology Journal, 2024, 5(4): 754-769.
洪源, 刘妍. 脑类器官在再生医学中的研究进展[J]. 合成生物学, 2024, 5(4): 754-769.
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URL: https://synbioj.cip.com.cn/EN/10.12211/2096-8280.2023-102
脑区 类型 | 年份 | 课题组 | 分化方法 | 参考文献 |
---|---|---|---|---|
大脑 皮层 | 2008 | Yoshiki Sasai | PSC在含有Dkk -1和Lefty-1的神经分化培养基中自组织形成SFEBq培养物 | [ |
2013 | Juergen A. Knoblich | 先将PSC重聚成拟胚体,并生成神经外胚层,随后将其嵌入Matrigel,在没有外源性生长因子的条件下悬浮培养 | [ | |
2015 | Sergiu P. Paşca | hiPSC形成拟胚体后使用Dorsomorphin和SB431542进行神经诱导分化,6天后转移至含FGF2和EGF的培养基中,体外培养第25天更换成BDNF和NT3 | [ | |
2016 | Hongjun Song & Guo-li Ming | iPSC重聚的拟胚体先在dorsomorphin和A-83的条件下培养7天,并用基质胶包埋后添加CHIR99021、WNT3A和SB431542因子培养1周后转移至微型旋转生物反应器继续培养 | [ | |
海马体 | 2015 | Yoshiki Sasai | hESC重聚形成SFEBq后,添加IWR1e和 SB431542培养18天,随后加入CHIR和BMP4诱导海马体分化 | [ |
纹状体 | 2020 | Sergiu P. Paşca | hiPSC形成拟胚体后,添加DMH1和SB431542培养6天,随后在第6~22天添加Activin A、IWP2和SR11237促进纹状体的分化 | [ |
2022 | Ma Lixiang | PSC重聚后在含LDN-193189和SB431542的培养基中培养10天,随后在purmorphamine的诱导下培养至第25天 | [ | |
中脑 | 2016 | Ng Huck-Hui | hESC重聚成拟胚体后第4天开始添加SHH-C25II和FGF8诱导中脑分化命运,神经外胚层出现后包埋类器官,转移至低吸附六孔板中培养 | [ |
2016 | Song Hongjun & Ming Guo-li | iPSC重聚后加入SHH、FGF-8、SB431542、LDN193189和CHIR99021诱导中脑命运,并在第14天时将其转移至微型旋转生物反应器继续培养 | [ | |
丘脑和 下丘脑 | 2016 | Song Hongjun & Ming Guo-li | iPSC重聚后先加入SB431542 和LDN193189,分化第4~7天,加入WNT3A、SHH和purmorphamine诱导下丘脑命运,随后持续添加FGF2和CNTF促进类器官成熟 | [ |
2019 | Park In-Hyun | hESC重聚后添加SB431542、LDN193189和insulin促进尾侧的神经诱导,第8天开始添加PD0325901和BMP7诱导丘脑分化 | [ | |
2021 | Song Hongjun & Ming Guo-li | hiPSC经过双SMAD抑制诱导神经外胚层命运,同时加入IWR1-endo、SAG、PMA和SHH促进弓状核分化,第12天开始与小鼠下丘脑星形胶质细胞共培养 | [ | |
小脑 | 2015 | Yoshiki Sasai | 将hESC重聚为SFEBq,第2~14天在含有胰岛素和SB431542的培养基中,持续添加重组人FGF2,并在后期加入FGF19和SDF1促进极性结构的形成 | [ |
2024 | Giorgia Quadrato | hiPSC重聚后第0~16天加入SB431542、Noggin、FGF8b和CHIR99021诱导后脑分化命运,并在第30天开始加入T3和BDNF促进后脑成熟,加入SDF1a完成小脑模式化 | [ | |
视网膜 | 2012 | Yoshiki Sasai | hESC重聚形成SFEBq后,在 IWR1e、FBS、SAG和CHIR99021的诱导下,自组织形成视网膜类器官 | [ |
2014 | M. Valeria Canto-Soler | 将hiPSC重聚后,分化第7天时用基质胶包埋,并在第4周手动分离神经视网膜结构域,从第42天开始向培养基中添加FBS、Taurine和GlutaMAX,在培养过程中,每天都需添加RA以促进光感受器的成熟 | [ |
Table1 The differentiation methods of brain region-specific organoids
脑区 类型 | 年份 | 课题组 | 分化方法 | 参考文献 |
---|---|---|---|---|
大脑 皮层 | 2008 | Yoshiki Sasai | PSC在含有Dkk -1和Lefty-1的神经分化培养基中自组织形成SFEBq培养物 | [ |
2013 | Juergen A. Knoblich | 先将PSC重聚成拟胚体,并生成神经外胚层,随后将其嵌入Matrigel,在没有外源性生长因子的条件下悬浮培养 | [ | |
2015 | Sergiu P. Paşca | hiPSC形成拟胚体后使用Dorsomorphin和SB431542进行神经诱导分化,6天后转移至含FGF2和EGF的培养基中,体外培养第25天更换成BDNF和NT3 | [ | |
2016 | Hongjun Song & Guo-li Ming | iPSC重聚的拟胚体先在dorsomorphin和A-83的条件下培养7天,并用基质胶包埋后添加CHIR99021、WNT3A和SB431542因子培养1周后转移至微型旋转生物反应器继续培养 | [ | |
海马体 | 2015 | Yoshiki Sasai | hESC重聚形成SFEBq后,添加IWR1e和 SB431542培养18天,随后加入CHIR和BMP4诱导海马体分化 | [ |
纹状体 | 2020 | Sergiu P. Paşca | hiPSC形成拟胚体后,添加DMH1和SB431542培养6天,随后在第6~22天添加Activin A、IWP2和SR11237促进纹状体的分化 | [ |
2022 | Ma Lixiang | PSC重聚后在含LDN-193189和SB431542的培养基中培养10天,随后在purmorphamine的诱导下培养至第25天 | [ | |
中脑 | 2016 | Ng Huck-Hui | hESC重聚成拟胚体后第4天开始添加SHH-C25II和FGF8诱导中脑分化命运,神经外胚层出现后包埋类器官,转移至低吸附六孔板中培养 | [ |
2016 | Song Hongjun & Ming Guo-li | iPSC重聚后加入SHH、FGF-8、SB431542、LDN193189和CHIR99021诱导中脑命运,并在第14天时将其转移至微型旋转生物反应器继续培养 | [ | |
丘脑和 下丘脑 | 2016 | Song Hongjun & Ming Guo-li | iPSC重聚后先加入SB431542 和LDN193189,分化第4~7天,加入WNT3A、SHH和purmorphamine诱导下丘脑命运,随后持续添加FGF2和CNTF促进类器官成熟 | [ |
2019 | Park In-Hyun | hESC重聚后添加SB431542、LDN193189和insulin促进尾侧的神经诱导,第8天开始添加PD0325901和BMP7诱导丘脑分化 | [ | |
2021 | Song Hongjun & Ming Guo-li | hiPSC经过双SMAD抑制诱导神经外胚层命运,同时加入IWR1-endo、SAG、PMA和SHH促进弓状核分化,第12天开始与小鼠下丘脑星形胶质细胞共培养 | [ | |
小脑 | 2015 | Yoshiki Sasai | 将hESC重聚为SFEBq,第2~14天在含有胰岛素和SB431542的培养基中,持续添加重组人FGF2,并在后期加入FGF19和SDF1促进极性结构的形成 | [ |
2024 | Giorgia Quadrato | hiPSC重聚后第0~16天加入SB431542、Noggin、FGF8b和CHIR99021诱导后脑分化命运,并在第30天开始加入T3和BDNF促进后脑成熟,加入SDF1a完成小脑模式化 | [ | |
视网膜 | 2012 | Yoshiki Sasai | hESC重聚形成SFEBq后,在 IWR1e、FBS、SAG和CHIR99021的诱导下,自组织形成视网膜类器官 | [ |
2014 | M. Valeria Canto-Soler | 将hiPSC重聚后,分化第7天时用基质胶包埋,并在第4周手动分离神经视网膜结构域,从第42天开始向培养基中添加FBS、Taurine和GlutaMAX,在培养过程中,每天都需添加RA以促进光感受器的成熟 | [ |
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