【原】研究消化系統(tǒng)疾病模型新工具-腸類器官

北京義翹神州 2024-10-16

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前言

現(xiàn)代醫(yī)學(xué)的發(fā)展將會(huì)獲得越來(lái)越復(fù)雜的數(shù)據(jù)，時(shí)間和空間上高度動(dòng)態(tài)的系統(tǒng)數(shù)據(jù)將會(huì)對(duì)診斷、治療和預(yù)測(cè)結(jié)果提供幫助。類器官有望成為治療各種胃腸道疾病的高價(jià)值系統(tǒng)，用于模擬免疫反應(yīng)、代謝機(jī)制、腫瘤發(fā)生與發(fā)展、感染性消化道疾病等。截止到2023年7月中旬，全球類器官的臨床研究超過(guò)170例，其中消化系統(tǒng)疾病的研究有70多例。為了助力類器官的培養(yǎng)和研究，義翹神州可提供自主研發(fā)的人源EGF、NOG、RSPO1等重組細(xì)胞因子產(chǎn)品。

01腸類器官研究進(jìn)展

腸類器官（Intestinal organoids）從人類腸道組織或干細(xì)胞中分離和培養(yǎng)構(gòu)建。通過(guò)在適當(dāng)?shù)呐囵B(yǎng)條件下處理這些細(xì)胞，可以形成三維的腸道結(jié)構(gòu)。當(dāng)充分成熟時(shí)，人類腸道類器官會(huì)重現(xiàn)出芽的隱窩和絨毛結(jié)構(gòu)域，分別含有增殖的ISC和祖細(xì)胞，以及分化的腸上皮細(xì)胞、杯狀細(xì)胞和潘氏細(xì)胞。

結(jié)腸類器官（colonic organoids）作為較早成功構(gòu)建的類器官模型之一，在體外模擬結(jié)腸上皮的微環(huán)境。目前有兩種較為成熟的、基于成體細(xì)胞的結(jié)腸類器官模型，分別衍生于富含亮氨酸重復(fù)序列G蛋白偶聯(lián)受體5陽(yáng)性（LGR5+）成體干細(xì)胞（ASC）和定向分化的誘導(dǎo)多能干細(xì)胞（iPSC）。

腸道類器官被廣泛用于研究腸道發(fā)育、功能和疾病。它們可以用于研究消化吸收、腸道感染、腸道炎癥、腸道腫瘤等疾病的發(fā)生機(jī)制，并用于藥物篩選和個(gè)體化醫(yī)療研究。腸道類器官在模擬人類腸道的復(fù)雜性和組織結(jié)構(gòu)方面具有一定的優(yōu)勢(shì)，因?yàn)樗鼈兏咏鎸?shí)的腸道環(huán)境。

盡管腸道類器官在研究中具有重要的應(yīng)用價(jià)值，但目前仍然存在著一些挑戰(zhàn)，如細(xì)胞培養(yǎng)的復(fù)雜性、缺乏完整的腸道微生物群落等。因此，腸道類器官仍在不斷發(fā)展和改進(jìn)，以更好地模擬和理解人類腸道的結(jié)構(gòu)和功能，在腸道生理病理學(xué)基礎(chǔ)研究、疾病建模、藥物篩選與開(kāi)發(fā)、再生醫(yī)學(xué)等領(lǐng)域具有廣闊應(yīng)用前景。

02細(xì)胞因子在腸類器官中的應(yīng)用

細(xì)胞因子作為類器官培養(yǎng)基的添加成分，對(duì)類器官培養(yǎng)起著重要作用。比如，EGF可以促進(jìn)腸上皮細(xì)胞增殖，Noggin使干細(xì)胞保持未分化的狀態(tài)并促進(jìn)增殖，R-spondin-1具體促進(jìn)腸干細(xì)胞增殖的能力。Li等人在進(jìn)行小鼠腸器官培養(yǎng)的時(shí)候，在培養(yǎng)基中加入50ng/mL EGF（貨號(hào)：50482-MNCH，義翹神州）、100ng/mL Noggin（貨號(hào)：50688-M02H，義翹神州）和500ng/mL R-spondin-1（貨號(hào)：11083-HNAS，義翹神州）。

相關(guān)文獻(xiàn)引用的細(xì)胞因子
應(yīng)用	因子	貨號(hào)	文獻(xiàn)
小鼠腸類器官培養(yǎng)	EGF	50482-MNCH	Doi: 10.1016/j.stemcr.2020.12.005
	NOG	50688-M02H
	RSPO1	11083-HNAS
腸腫瘤類器官的培養(yǎng)	EGF	50482-MNCH	Doi: 10.3389/fonc.2022.855674
	NOG	50688-M02H
	RSPO1	11083-HNAS
顱咽管瘤類器官培養(yǎng)	EGF	10605-HNAE	Doi: 10.3390/biom12121744
顱咽管瘤類器官培養(yǎng)	FGF10	10573-HNAE	Doi: 10.3390/biom12121744
滋養(yǎng)層類器官培養(yǎng)	RSPO1	11083-HNAS	Doi: 10.1016/j.xcrm.2022.100849
滋養(yǎng)層類器官培養(yǎng)	HGF	10463-HNAS	Doi: 10.1016/j.xcrm.2022.100849

?義翹神州細(xì)胞因子產(chǎn)品數(shù)據(jù)

Human RSPO1 Protein, Cat: 11083-HNAS

高純度：

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

高批間一致性

Induce activation of ?catenin response in a Topflash Luciferase assay using HEK293T human embryonic kidney cells.

Human Noggin Protein, Cat: 10267-HNAH

高純度：

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

高批間一致性

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

腸類器官培養(yǎng)相關(guān)的細(xì)胞因子
貨號(hào)	靶點(diǎn)	內(nèi)毒素	純度及活性
10605-HNAE	EGF	<5 EU/mg	≥95%^☆, Active
GMP-10605-HNAE	EGF	<5 EU/mg	≥95%^☆, Active
GMP-10014-HNAE	FGF2	<10 EU/mg	≥95%, Active
10210-H07E	FGF7	<0.01 EU/μg	≥95%^☆, Active
10267-HNAH	NOG	<10 EU/mg	≥95%^☆, Active
10007-HNAH	CSF3	<10 EU/mg	≥95%^☆, Active
10236-H02H	EPO	<10 EU/mg	≥95%^☆, Active
10573-HNAE	FGF10	<5 EU/mg	≥95%^☆, Active
11858-HNAE	IL3	<5 EU/mg	≥95%^☆, Active
GMP-11858-HNAE	IL3	<5 EU/mg	≥95%^☆, Active
10451-HNAE	KITLG	<10 EU/mg	≥95%^☆, Active
11066-HNAH	VEGFA	<10 EU/mg	≥95%^☆, Active
10424-H08H	VTN	<10 EU/mg	≥95%, Active
10429-HNAH	INHBA	<10 EU/mg	≥95%^☆, Active
GMP-10429-HNAH	INHBA	<10 EU/mg	≥95%^☆, Active
10463-HNAS	HGF	<0.01 EU/μg	≥95%^☆, Active
11083-HNAS	RSPO1	<10 EU/mg	≥95%^☆, Active
11648-H08H	JAG1	<10 EU/mg	≥95%^☆, Active
10452-HNAH	OSM	<10 EU/mg	≥95%^☆, Active
GMP-10452-HNAH	OSM	<5 EU/mg	≥95%^☆, Active
10573-HNAE	FGF10	<5 EU/mg	≥95%^☆, Active
GMP-10573-HNAE	FGF10	<5 EU/mg	≥95%^☆, Active

☆：SDS-PAGE & SEC-HPLC

【參考文獻(xiàn)】

1. Taelman, J., Diaz, M., & Guiu, J. Human Intestinal Organoids: Promise and Challenge. Frontiers in cell and developmental biology, 2022. https:///10.3389/fcell.2022.854740

2. Kakni, P., et al. PSC-derived intestinal organoids with apical-out orientation as a tool to study nutrient uptake, drug absorption and metabolism. Frontiers in molecular biosciences, 2023. https:///10.3389/fmolb.2023.1102209

3. Rubert, J., et al. Intestinal Organoids: A Tool for Modelling Diet-Microbiome-Host Interactions. Trends in endocrinology and metabolism: TEM, 2022. https:///10.1016/j.tem.2020.02.004

4. Günther, C., et al. Organoids in gastrointestinal diseases: from experimental models to clinical translation. Gut, 2022. https:///10.1136/gutjnl-2021-326560

5. Wang, Q., et al. Applications of human organoids in the personalized treatment for digestive diseases. Signal transduction and targeted therapy, 2022. https:///10.1038/s41392-022-01194-6

6. Abud, H. E., et al. Source and Impact of the EGF Family of Ligands on Intestinal Stem Cells. Frontiers in cell and developmental biology, 2021. https:///10.3389/fcell.2021.685665

7. Krause, C., Guzman, A., & Knaus, P. Noggin. The international journal of biochemistry & cell biology, 2011.

https:///10.1016/j.biocel.2011.01.007

8. Li, Y., et al. Bach2 Deficiency Promotes Intestinal Epithelial Regeneration by Accelerating DNA Repair in Intestinal Stem Cells. Stem cell reports, 2021. https:///10.1016/j.stemcr.2020.12.005

9. Chen, L., et al. Molecular Biomarker of Drug Resistance Developed From Patient-Derived Organoids Predicts Survival of Colorectal Cancer Patients. Frontiers in oncology, 2022. https:///10.3389/fonc.2022.855674

10. Tang, M., et al. Evaluation of B7-H3 Targeted Immunotherapy in a 3D Organoid Model of Craniopharyngioma. Biomolecules, 2022. https:///10.3390/biom12121744

11. Ruan, D., et al. Human early syncytiotrophoblasts are highly susceptible to SARS-CoV-2 infection. Cell reports. Medicine, 2022. https:///10.1016/j.xcrm.2022.100849