INTESTINAL ORGANOID IMMUNE-CONTROL INTEGRATED PLATFORM FOR THERAGNOSIS OF MICROBIOME AND IMMUNE CELL
It was identified that intestinal organoids derived human blood and endocytes of the present invention expressed the intestinal differentiation markers CGA, CDX2, LYZ, ECAD, KLF5, MUC2, Ki67, VIL, LGR5, SOX9, VIM, and SMA, thereby effectively reflecting intestinal conditions and can assay intestinal...
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| creator | YANG, Seung Cheon PARK, Jin Sil JEONG, Ha Yeon JHUN, Joo Yeon CHOI, Jeong Won LEE, Bo In KIM, Seung Jun LEE, Seung Yoon CHO, Mi La KIM, Ju Ryun CHO, Keun Hyung KIM, Ji Young PARK, Sung Hwan LEE, Han Hee KIM, Sol JU, Ji Hyeon |
| description | It was identified that intestinal organoids derived human blood and endocytes of the present invention expressed the intestinal differentiation markers CGA, CDX2, LYZ, ECAD, KLF5, MUC2, Ki67, VIL, LGR5, SOX9, VIM, and SMA, thereby effectively reflecting intestinal conditions and can assay intestinal protection and intestinal secretions according to treatment with microbiomes. In addition, the (Bifidobacterium microbiome RAPO of the present invention was identified to upregulate the expression of IL-10 and REG3A and induce the expression of lysozyme, E-cadherin, and CGA and the proliferation of intestinal crypts in the intestinal organoids. Furthermore, intestinal organoids of the present invention were examined for responses to treatment with homologous PBMC to identify the reactivity of transplant rejection. In addition, an inflammatory bowel disease simulated avatar model of the present invention was identified to allow for effectively engrafting human blood immune cells thereto and induce the development of inflammatory bowel disease and the injury of intestinal tissues, thereby effectively reflecting diseased conditions of patients. Also, it was identified that injection of PBMC from patients with inflammatory bowel disease advanced the inflammatory bowel diseases, compared to injection of PBMC from normal persons and treatment with candidate materials could palliate the inflammatory bowel diseases, whereby therapeutic agents customized for patients can be screened.
Il a été identifié que les organoïdes intestinaux dérivés du sang humain et les endocytes de la présente invention expriment les marqueurs de différenciation intestinale CGA, CDX2, LYZ, ECAD, KLF5, MUC2, Ki67, VIL, LGR5, SOX9, VIM et SMA, ce qui permet de prendre en compte efficacement les affections intestinales et de doser la protection intestinale et les sécrétions intestinales selon un traitement au moyen de microbiomes. De plus, le Bifidobacterium microbiome RAPO de la présente invention a été identifié pour réguler à la hausse l'expression de l'IL-10 et REG3A et induire l'expression du lysozyme, E-cadhérine, et CGA et la prolifération des cryptes intestinales dans les organoïdes intestinaux. De plus, les organoïdes intestinaux de la présente invention ont été examinés pour des réponses au traitement par des PBMC homologues pour identifier la réactivité du rejet de greffe. De plus, un modèle d'avatar simulé de maladie intestinale inflammatoire de la présente invention a été identifié p |
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| fullrecord | <record><control><sourceid>epo_EVB</sourceid><recordid>TN_cdi_epo_espacenet_WO2022158882A1</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>WO2022158882A1</sourcerecordid><originalsourceid>FETCH-epo_espacenet_WO2022158882A13</originalsourceid><addsrcrecordid>eNqNjLEKwjAQQLs4iPoPB84FGxG6xvTaHiR3kp44lqJxEi3U_0cF3V3eWx5vnl2IFTslth4kNpaFKqAQjoy5E9YoHj5JE61iBQdvtZYY4A3QFqNtWDrqQGoI5KLsSQKC5d8EHHq_zGbX4Tal1deLbF2jujZP46NP0zic0z09-5OYjTHFrixLY4vtf9ULWkA1wQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>patent</recordtype></control><display><type>patent</type><title>INTESTINAL ORGANOID IMMUNE-CONTROL INTEGRATED PLATFORM FOR THERAGNOSIS OF MICROBIOME AND IMMUNE CELL</title><source>esp@cenet</source><creator>YANG, Seung Cheon ; PARK, Jin Sil ; JEONG, Ha Yeon ; JHUN, Joo Yeon ; CHOI, Jeong Won ; LEE, Bo In ; KIM, Seung Jun ; LEE, Seung Yoon ; CHO, Mi La ; KIM, Ju Ryun ; CHO, Keun Hyung ; KIM, Ji Young ; PARK, Sung Hwan ; LEE, Han Hee ; KIM, Sol ; JU, Ji Hyeon</creator><creatorcontrib>YANG, Seung Cheon ; PARK, Jin Sil ; JEONG, Ha Yeon ; JHUN, Joo Yeon ; CHOI, Jeong Won ; LEE, Bo In ; KIM, Seung Jun ; LEE, Seung Yoon ; CHO, Mi La ; KIM, Ju Ryun ; CHO, Keun Hyung ; KIM, Ji Young ; PARK, Sung Hwan ; LEE, Han Hee ; KIM, Sol ; JU, Ji Hyeon</creatorcontrib><description>It was identified that intestinal organoids derived human blood and endocytes of the present invention expressed the intestinal differentiation markers CGA, CDX2, LYZ, ECAD, KLF5, MUC2, Ki67, VIL, LGR5, SOX9, VIM, and SMA, thereby effectively reflecting intestinal conditions and can assay intestinal protection and intestinal secretions according to treatment with microbiomes. In addition, the (Bifidobacterium microbiome RAPO of the present invention was identified to upregulate the expression of IL-10 and REG3A and induce the expression of lysozyme, E-cadherin, and CGA and the proliferation of intestinal crypts in the intestinal organoids. Furthermore, intestinal organoids of the present invention were examined for responses to treatment with homologous PBMC to identify the reactivity of transplant rejection. In addition, an inflammatory bowel disease simulated avatar model of the present invention was identified to allow for effectively engrafting human blood immune cells thereto and induce the development of inflammatory bowel disease and the injury of intestinal tissues, thereby effectively reflecting diseased conditions of patients. Also, it was identified that injection of PBMC from patients with inflammatory bowel disease advanced the inflammatory bowel diseases, compared to injection of PBMC from normal persons and treatment with candidate materials could palliate the inflammatory bowel diseases, whereby therapeutic agents customized for patients can be screened.
Il a été identifié que les organoïdes intestinaux dérivés du sang humain et les endocytes de la présente invention expriment les marqueurs de différenciation intestinale CGA, CDX2, LYZ, ECAD, KLF5, MUC2, Ki67, VIL, LGR5, SOX9, VIM et SMA, ce qui permet de prendre en compte efficacement les affections intestinales et de doser la protection intestinale et les sécrétions intestinales selon un traitement au moyen de microbiomes. De plus, le Bifidobacterium microbiome RAPO de la présente invention a été identifié pour réguler à la hausse l'expression de l'IL-10 et REG3A et induire l'expression du lysozyme, E-cadhérine, et CGA et la prolifération des cryptes intestinales dans les organoïdes intestinaux. De plus, les organoïdes intestinaux de la présente invention ont été examinés pour des réponses au traitement par des PBMC homologues pour identifier la réactivité du rejet de greffe. De plus, un modèle d'avatar simulé de maladie intestinale inflammatoire de la présente invention a été identifié pour permettre de greffer efficacement des cellules immunitaires du sang humaines sur celui-ci et induire le développement d'une maladie intestinale inflammatoire et la lésion de tissus intestinaux, ce qui permet de prendre en compte efficacement les états pathologiques des patients. Il a également été identifié que l'injection de PBMC de patients atteints d'une maladie intestinale inflammatoire fait progresser les maladies intestinales inflammatoires, par comparaison à l'injection de PBMC provenant de personnes normales et le traitement par des matériaux candidats pourrait pallier les maladies intestinales inflammatoires, ce par quoi des agents thérapeutiques personnalisés pour des patients peuvent être criblés.
본 발명의 인간 혈액 및 장세포 유래의 장오가노이드는, 장 분화 마커인 CGA, CDX2, LYZ, ECAD, KLF5, MUC2, Ki67, VIL, LGR5, SOX9, VIM 및 SMA가 발현되어, 효과적으로 장내의 상태를 반영하고, 마이크로바이옴처리에 따라, 장보호, 장분비능을 평가할 수 있는 것을 확인하였다. 또한, 본 발명의 비피도박테리엄 마이크로바이옴(Bifidobacterium microbiome) RAPO는, 장오가노이드에서 IL-10 및 REG3A의 발현을 증가시키고, 라이소자임, E-cadherin 및 CGA의 발현을 유도하고, 장 Crypt증식을 유도하는 것을 확인하였다. 또한, 본 발명의 장 오가노이드에, 동종의 PBMC 처리에 따른 반응성을 확인하여, 이식거부반응에 대한 반응성을 확인하였다. 또한, 본 발명의 염증성 장질환 모사 아바타모델은, 혈액 내 인간 면역세포가 효과적으로 생착하며, 염증성 장질환의 발달 및 장조직의 손상을 유도하여, 환자의 질병 상태를 효과적으로 반영하는 것을 확인하였다. 또한, 정상인의 PBMC 주입과 비교하여, 염증성 장질환 환자의 PBMC를 주입하였을 때, 염증성 장질환이 발달되며, 후보물질의 처리로 염증성 장질환을 개선시킬 수 있는 것을 확인하여, 환자 맞춤형 치료제를 스크리닝 할 수 있는 것을 확인하였다.</description><language>eng ; fre ; kor</language><subject>AGRICULTURE ; ANIMAL HUSBANDRY ; BEER ; BIOCHEMISTRY ; CARE OF BIRDS, FISHES, INSECTS ; CHEMISTRY ; COMPOSITIONS THEREOF ; CULTURE MEDIA ; ENZYMOLOGY ; FISHING ; FORESTRY ; HUMAN NECESSITIES ; HUNTING ; INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIRCHEMICAL OR PHYSICAL PROPERTIES ; MEASURING ; METALLURGY ; MICROBIOLOGY ; MICROORGANISMS OR ENZYMES ; MUTATION OR GENETIC ENGINEERING ; NEW BREEDS OF ANIMALS ; PHYSICS ; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS ; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR ; SPIRITS ; TESTING ; TRAPPING ; VINEGAR ; WINE</subject><creationdate>2022</creationdate><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://worldwide.espacenet.com/publicationDetails/biblio?FT=D&date=20220728&DB=EPODOC&CC=WO&NR=2022158882A1$$EHTML$$P50$$Gepo$$Hfree_for_read</linktohtml><link.rule.ids>230,308,780,885,25564,76547</link.rule.ids><linktorsrc>$$Uhttps://worldwide.espacenet.com/publicationDetails/biblio?FT=D&date=20220728&DB=EPODOC&CC=WO&NR=2022158882A1$$EView_record_in_European_Patent_Office$$FView_record_in_$$GEuropean_Patent_Office$$Hfree_for_read</linktorsrc></links><search><creatorcontrib>YANG, Seung Cheon</creatorcontrib><creatorcontrib>PARK, Jin Sil</creatorcontrib><creatorcontrib>JEONG, Ha Yeon</creatorcontrib><creatorcontrib>JHUN, Joo Yeon</creatorcontrib><creatorcontrib>CHOI, Jeong Won</creatorcontrib><creatorcontrib>LEE, Bo In</creatorcontrib><creatorcontrib>KIM, Seung Jun</creatorcontrib><creatorcontrib>LEE, Seung Yoon</creatorcontrib><creatorcontrib>CHO, Mi La</creatorcontrib><creatorcontrib>KIM, Ju Ryun</creatorcontrib><creatorcontrib>CHO, Keun Hyung</creatorcontrib><creatorcontrib>KIM, Ji Young</creatorcontrib><creatorcontrib>PARK, Sung Hwan</creatorcontrib><creatorcontrib>LEE, Han Hee</creatorcontrib><creatorcontrib>KIM, Sol</creatorcontrib><creatorcontrib>JU, Ji Hyeon</creatorcontrib><title>INTESTINAL ORGANOID IMMUNE-CONTROL INTEGRATED PLATFORM FOR THERAGNOSIS OF MICROBIOME AND IMMUNE CELL</title><description>It was identified that intestinal organoids derived human blood and endocytes of the present invention expressed the intestinal differentiation markers CGA, CDX2, LYZ, ECAD, KLF5, MUC2, Ki67, VIL, LGR5, SOX9, VIM, and SMA, thereby effectively reflecting intestinal conditions and can assay intestinal protection and intestinal secretions according to treatment with microbiomes. In addition, the (Bifidobacterium microbiome RAPO of the present invention was identified to upregulate the expression of IL-10 and REG3A and induce the expression of lysozyme, E-cadherin, and CGA and the proliferation of intestinal crypts in the intestinal organoids. Furthermore, intestinal organoids of the present invention were examined for responses to treatment with homologous PBMC to identify the reactivity of transplant rejection. In addition, an inflammatory bowel disease simulated avatar model of the present invention was identified to allow for effectively engrafting human blood immune cells thereto and induce the development of inflammatory bowel disease and the injury of intestinal tissues, thereby effectively reflecting diseased conditions of patients. Also, it was identified that injection of PBMC from patients with inflammatory bowel disease advanced the inflammatory bowel diseases, compared to injection of PBMC from normal persons and treatment with candidate materials could palliate the inflammatory bowel diseases, whereby therapeutic agents customized for patients can be screened.
Il a été identifié que les organoïdes intestinaux dérivés du sang humain et les endocytes de la présente invention expriment les marqueurs de différenciation intestinale CGA, CDX2, LYZ, ECAD, KLF5, MUC2, Ki67, VIL, LGR5, SOX9, VIM et SMA, ce qui permet de prendre en compte efficacement les affections intestinales et de doser la protection intestinale et les sécrétions intestinales selon un traitement au moyen de microbiomes. De plus, le Bifidobacterium microbiome RAPO de la présente invention a été identifié pour réguler à la hausse l'expression de l'IL-10 et REG3A et induire l'expression du lysozyme, E-cadhérine, et CGA et la prolifération des cryptes intestinales dans les organoïdes intestinaux. De plus, les organoïdes intestinaux de la présente invention ont été examinés pour des réponses au traitement par des PBMC homologues pour identifier la réactivité du rejet de greffe. De plus, un modèle d'avatar simulé de maladie intestinale inflammatoire de la présente invention a été identifié pour permettre de greffer efficacement des cellules immunitaires du sang humaines sur celui-ci et induire le développement d'une maladie intestinale inflammatoire et la lésion de tissus intestinaux, ce qui permet de prendre en compte efficacement les états pathologiques des patients. Il a également été identifié que l'injection de PBMC de patients atteints d'une maladie intestinale inflammatoire fait progresser les maladies intestinales inflammatoires, par comparaison à l'injection de PBMC provenant de personnes normales et le traitement par des matériaux candidats pourrait pallier les maladies intestinales inflammatoires, ce par quoi des agents thérapeutiques personnalisés pour des patients peuvent être criblés.
본 발명의 인간 혈액 및 장세포 유래의 장오가노이드는, 장 분화 마커인 CGA, CDX2, LYZ, ECAD, KLF5, MUC2, Ki67, VIL, LGR5, SOX9, VIM 및 SMA가 발현되어, 효과적으로 장내의 상태를 반영하고, 마이크로바이옴처리에 따라, 장보호, 장분비능을 평가할 수 있는 것을 확인하였다. 또한, 본 발명의 비피도박테리엄 마이크로바이옴(Bifidobacterium microbiome) RAPO는, 장오가노이드에서 IL-10 및 REG3A의 발현을 증가시키고, 라이소자임, E-cadherin 및 CGA의 발현을 유도하고, 장 Crypt증식을 유도하는 것을 확인하였다. 또한, 본 발명의 장 오가노이드에, 동종의 PBMC 처리에 따른 반응성을 확인하여, 이식거부반응에 대한 반응성을 확인하였다. 또한, 본 발명의 염증성 장질환 모사 아바타모델은, 혈액 내 인간 면역세포가 효과적으로 생착하며, 염증성 장질환의 발달 및 장조직의 손상을 유도하여, 환자의 질병 상태를 효과적으로 반영하는 것을 확인하였다. 또한, 정상인의 PBMC 주입과 비교하여, 염증성 장질환 환자의 PBMC를 주입하였을 때, 염증성 장질환이 발달되며, 후보물질의 처리로 염증성 장질환을 개선시킬 수 있는 것을 확인하여, 환자 맞춤형 치료제를 스크리닝 할 수 있는 것을 확인하였다.</description><subject>AGRICULTURE</subject><subject>ANIMAL HUSBANDRY</subject><subject>BEER</subject><subject>BIOCHEMISTRY</subject><subject>CARE OF BIRDS, FISHES, INSECTS</subject><subject>CHEMISTRY</subject><subject>COMPOSITIONS THEREOF</subject><subject>CULTURE MEDIA</subject><subject>ENZYMOLOGY</subject><subject>FISHING</subject><subject>FORESTRY</subject><subject>HUMAN NECESSITIES</subject><subject>HUNTING</subject><subject>INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIRCHEMICAL OR PHYSICAL PROPERTIES</subject><subject>MEASURING</subject><subject>METALLURGY</subject><subject>MICROBIOLOGY</subject><subject>MICROORGANISMS OR ENZYMES</subject><subject>MUTATION OR GENETIC ENGINEERING</subject><subject>NEW BREEDS OF ANIMALS</subject><subject>PHYSICS</subject><subject>PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS</subject><subject>REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR</subject><subject>SPIRITS</subject><subject>TESTING</subject><subject>TRAPPING</subject><subject>VINEGAR</subject><subject>WINE</subject><fulltext>true</fulltext><rsrctype>patent</rsrctype><creationdate>2022</creationdate><recordtype>patent</recordtype><sourceid>EVB</sourceid><recordid>eNqNjLEKwjAQQLs4iPoPB84FGxG6xvTaHiR3kp44lqJxEi3U_0cF3V3eWx5vnl2IFTslth4kNpaFKqAQjoy5E9YoHj5JE61iBQdvtZYY4A3QFqNtWDrqQGoI5KLsSQKC5d8EHHq_zGbX4Tal1deLbF2jujZP46NP0zic0z09-5OYjTHFrixLY4vtf9ULWkA1wQ</recordid><startdate>20220728</startdate><enddate>20220728</enddate><creator>YANG, Seung Cheon</creator><creator>PARK, Jin Sil</creator><creator>JEONG, Ha Yeon</creator><creator>JHUN, Joo Yeon</creator><creator>CHOI, Jeong Won</creator><creator>LEE, Bo In</creator><creator>KIM, Seung Jun</creator><creator>LEE, Seung Yoon</creator><creator>CHO, Mi La</creator><creator>KIM, Ju Ryun</creator><creator>CHO, Keun Hyung</creator><creator>KIM, Ji Young</creator><creator>PARK, Sung Hwan</creator><creator>LEE, Han Hee</creator><creator>KIM, Sol</creator><creator>JU, Ji Hyeon</creator><scope>EVB</scope></search><sort><creationdate>20220728</creationdate><title>INTESTINAL ORGANOID IMMUNE-CONTROL INTEGRATED PLATFORM FOR THERAGNOSIS OF MICROBIOME AND IMMUNE CELL</title><author>YANG, Seung Cheon ; PARK, Jin Sil ; JEONG, Ha Yeon ; JHUN, Joo Yeon ; CHOI, Jeong Won ; LEE, Bo In ; KIM, Seung Jun ; LEE, Seung Yoon ; CHO, Mi La ; KIM, Ju Ryun ; CHO, Keun Hyung ; KIM, Ji Young ; PARK, Sung Hwan ; LEE, Han Hee ; KIM, Sol ; JU, Ji Hyeon</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-epo_espacenet_WO2022158882A13</frbrgroupid><rsrctype>patents</rsrctype><prefilter>patents</prefilter><language>eng ; fre ; kor</language><creationdate>2022</creationdate><topic>AGRICULTURE</topic><topic>ANIMAL HUSBANDRY</topic><topic>BEER</topic><topic>BIOCHEMISTRY</topic><topic>CARE OF BIRDS, FISHES, INSECTS</topic><topic>CHEMISTRY</topic><topic>COMPOSITIONS THEREOF</topic><topic>CULTURE MEDIA</topic><topic>ENZYMOLOGY</topic><topic>FISHING</topic><topic>FORESTRY</topic><topic>HUMAN NECESSITIES</topic><topic>HUNTING</topic><topic>INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIRCHEMICAL OR PHYSICAL PROPERTIES</topic><topic>MEASURING</topic><topic>METALLURGY</topic><topic>MICROBIOLOGY</topic><topic>MICROORGANISMS OR ENZYMES</topic><topic>MUTATION OR GENETIC ENGINEERING</topic><topic>NEW BREEDS OF ANIMALS</topic><topic>PHYSICS</topic><topic>PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS</topic><topic>REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR</topic><topic>SPIRITS</topic><topic>TESTING</topic><topic>TRAPPING</topic><topic>VINEGAR</topic><topic>WINE</topic><toplevel>online_resources</toplevel><creatorcontrib>YANG, Seung Cheon</creatorcontrib><creatorcontrib>PARK, Jin Sil</creatorcontrib><creatorcontrib>JEONG, Ha Yeon</creatorcontrib><creatorcontrib>JHUN, Joo Yeon</creatorcontrib><creatorcontrib>CHOI, Jeong Won</creatorcontrib><creatorcontrib>LEE, Bo In</creatorcontrib><creatorcontrib>KIM, Seung Jun</creatorcontrib><creatorcontrib>LEE, Seung Yoon</creatorcontrib><creatorcontrib>CHO, Mi La</creatorcontrib><creatorcontrib>KIM, Ju Ryun</creatorcontrib><creatorcontrib>CHO, Keun Hyung</creatorcontrib><creatorcontrib>KIM, Ji Young</creatorcontrib><creatorcontrib>PARK, Sung Hwan</creatorcontrib><creatorcontrib>LEE, Han Hee</creatorcontrib><creatorcontrib>KIM, Sol</creatorcontrib><creatorcontrib>JU, Ji Hyeon</creatorcontrib><collection>esp@cenet</collection></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>YANG, Seung Cheon</au><au>PARK, Jin Sil</au><au>JEONG, Ha Yeon</au><au>JHUN, Joo Yeon</au><au>CHOI, Jeong Won</au><au>LEE, Bo In</au><au>KIM, Seung Jun</au><au>LEE, Seung Yoon</au><au>CHO, Mi La</au><au>KIM, Ju Ryun</au><au>CHO, Keun Hyung</au><au>KIM, Ji Young</au><au>PARK, Sung Hwan</au><au>LEE, Han Hee</au><au>KIM, Sol</au><au>JU, Ji Hyeon</au><format>patent</format><genre>patent</genre><ristype>GEN</ristype><title>INTESTINAL ORGANOID IMMUNE-CONTROL INTEGRATED PLATFORM FOR THERAGNOSIS OF MICROBIOME AND IMMUNE CELL</title><date>2022-07-28</date><risdate>2022</risdate><abstract>It was identified that intestinal organoids derived human blood and endocytes of the present invention expressed the intestinal differentiation markers CGA, CDX2, LYZ, ECAD, KLF5, MUC2, Ki67, VIL, LGR5, SOX9, VIM, and SMA, thereby effectively reflecting intestinal conditions and can assay intestinal protection and intestinal secretions according to treatment with microbiomes. In addition, the (Bifidobacterium microbiome RAPO of the present invention was identified to upregulate the expression of IL-10 and REG3A and induce the expression of lysozyme, E-cadherin, and CGA and the proliferation of intestinal crypts in the intestinal organoids. Furthermore, intestinal organoids of the present invention were examined for responses to treatment with homologous PBMC to identify the reactivity of transplant rejection. In addition, an inflammatory bowel disease simulated avatar model of the present invention was identified to allow for effectively engrafting human blood immune cells thereto and induce the development of inflammatory bowel disease and the injury of intestinal tissues, thereby effectively reflecting diseased conditions of patients. Also, it was identified that injection of PBMC from patients with inflammatory bowel disease advanced the inflammatory bowel diseases, compared to injection of PBMC from normal persons and treatment with candidate materials could palliate the inflammatory bowel diseases, whereby therapeutic agents customized for patients can be screened.
Il a été identifié que les organoïdes intestinaux dérivés du sang humain et les endocytes de la présente invention expriment les marqueurs de différenciation intestinale CGA, CDX2, LYZ, ECAD, KLF5, MUC2, Ki67, VIL, LGR5, SOX9, VIM et SMA, ce qui permet de prendre en compte efficacement les affections intestinales et de doser la protection intestinale et les sécrétions intestinales selon un traitement au moyen de microbiomes. De plus, le Bifidobacterium microbiome RAPO de la présente invention a été identifié pour réguler à la hausse l'expression de l'IL-10 et REG3A et induire l'expression du lysozyme, E-cadhérine, et CGA et la prolifération des cryptes intestinales dans les organoïdes intestinaux. De plus, les organoïdes intestinaux de la présente invention ont été examinés pour des réponses au traitement par des PBMC homologues pour identifier la réactivité du rejet de greffe. De plus, un modèle d'avatar simulé de maladie intestinale inflammatoire de la présente invention a été identifié pour permettre de greffer efficacement des cellules immunitaires du sang humaines sur celui-ci et induire le développement d'une maladie intestinale inflammatoire et la lésion de tissus intestinaux, ce qui permet de prendre en compte efficacement les états pathologiques des patients. Il a également été identifié que l'injection de PBMC de patients atteints d'une maladie intestinale inflammatoire fait progresser les maladies intestinales inflammatoires, par comparaison à l'injection de PBMC provenant de personnes normales et le traitement par des matériaux candidats pourrait pallier les maladies intestinales inflammatoires, ce par quoi des agents thérapeutiques personnalisés pour des patients peuvent être criblés.
본 발명의 인간 혈액 및 장세포 유래의 장오가노이드는, 장 분화 마커인 CGA, CDX2, LYZ, ECAD, KLF5, MUC2, Ki67, VIL, LGR5, SOX9, VIM 및 SMA가 발현되어, 효과적으로 장내의 상태를 반영하고, 마이크로바이옴처리에 따라, 장보호, 장분비능을 평가할 수 있는 것을 확인하였다. 또한, 본 발명의 비피도박테리엄 마이크로바이옴(Bifidobacterium microbiome) RAPO는, 장오가노이드에서 IL-10 및 REG3A의 발현을 증가시키고, 라이소자임, E-cadherin 및 CGA의 발현을 유도하고, 장 Crypt증식을 유도하는 것을 확인하였다. 또한, 본 발명의 장 오가노이드에, 동종의 PBMC 처리에 따른 반응성을 확인하여, 이식거부반응에 대한 반응성을 확인하였다. 또한, 본 발명의 염증성 장질환 모사 아바타모델은, 혈액 내 인간 면역세포가 효과적으로 생착하며, 염증성 장질환의 발달 및 장조직의 손상을 유도하여, 환자의 질병 상태를 효과적으로 반영하는 것을 확인하였다. 또한, 정상인의 PBMC 주입과 비교하여, 염증성 장질환 환자의 PBMC를 주입하였을 때, 염증성 장질환이 발달되며, 후보물질의 처리로 염증성 장질환을 개선시킬 수 있는 것을 확인하여, 환자 맞춤형 치료제를 스크리닝 할 수 있는 것을 확인하였다.</abstract><oa>free_for_read</oa></addata></record> |
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| language | eng ; fre ; kor |
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| subjects | AGRICULTURE ANIMAL HUSBANDRY BEER BIOCHEMISTRY CARE OF BIRDS, FISHES, INSECTS CHEMISTRY COMPOSITIONS THEREOF CULTURE MEDIA ENZYMOLOGY FISHING FORESTRY HUMAN NECESSITIES HUNTING INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIRCHEMICAL OR PHYSICAL PROPERTIES MEASURING METALLURGY MICROBIOLOGY MICROORGANISMS OR ENZYMES MUTATION OR GENETIC ENGINEERING NEW BREEDS OF ANIMALS PHYSICS PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR SPIRITS TESTING TRAPPING VINEGAR WINE |
| title | INTESTINAL ORGANOID IMMUNE-CONTROL INTEGRATED PLATFORM FOR THERAGNOSIS OF MICROBIOME AND IMMUNE CELL |
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