序号 专利名 申请号 申请日 公开(公告)号 公开(公告)日 发明人
1 类胚体,基于细胞系的人工囊胚 CN201480028434.0 2014-04-16 CN105683363A 2016-06-15 尼古拉斯·克莱蒙特·里夫隆; 克莱门斯·安东尼·范布利特尔斯维吉克; 尼尔斯·耶耶森; 埃里克·雅各布·夫里耶
发明涉及用于制造至少双层的细胞聚集体和/或人工囊胚和/或被称为类胚体的进一步发育的类胚体的方法,所述方法包括从至少一个滋养细胞和至少一个多能和/或全能细胞形成双层的细胞聚集体,以及培养所述聚集体以获得人工囊胚。这种人工囊胚具有围绕囊胚腔的滋养外胚层样组织和内部细胞团样组织。所述细胞聚集体可以从全能或多能干细胞类型或诱导的多能干细胞类型与滋养干细胞的组合来形成。类胚体的形成可以通过将所述细胞聚集体在优选地包含Rho/ROCK抑制剂、Wnt途径调节物、PKA途径调节物、PKC途径调节物、MAPK途径调节物、STAT途径调节物、Akt途径调节物、Tgf途径调节物和Hippo途径调节物中的一种或多种的培养基中培养来实现。本发明还涉及用于使至少双层的细胞聚集体生长成人工囊胚和生长成进一步发育的类胚体、胎儿或活动物的方法。本发明还涉及包含所提到的化合物和/或细胞聚集体的体外细胞培养物。
2 地中海贻贝的雌核发育诱导方法 CN201510959564.2 2015-12-21 CN106906204A 2017-06-30 褚方强
发明涉及一种地中海贻贝的雌核发育诱导方法,采用电刺激法,电刺激前先将卵子移入电刺激缓冲液中平衡2min,调好电脉冲仪参数,用吸管吸取1ml卵子放入电击杯中,即可进行电刺激处理;所述电刺激缓冲液为山梨醇缓冲液,具体成分为:含有0.25 mmol/L Mg(C2H3O2)2·4H2O,0.5 mol/L Hepes,0.1 mmol/L Ca(C2H3O2)2H2O,1%BSA,0.25 mmol/L山梨醇;所述电脉冲仪参数为场强1.25 kv/cm,电容4µF,2次电脉冲。所述电刺激时的卵子密度为6×104个/ml。本发明的方法简单有效,经电刺激诱导后,地中海贻贝的卵裂率可达到28%以上,胚胎存活率可达到98%以上。
3 仿刺参的雌核发育诱导方法 CN201510959560.4 2015-12-21 CN106906203A 2017-06-30 褚方强
发明涉及一种仿刺参的雌核发育诱导方法,采用电刺激法,电刺激前先将卵子移入电刺激缓冲液中平衡2min,调好电脉冲仪参数,用吸管吸取1ml卵子放入电击杯中,即可进行电刺激处理;所述电刺激缓冲液为Zimmerman氏缓冲液,具体成分为:0.1mmol/L Ca(C2H3O2)2H2O,1mmol/L K2HPO4,0.5mmol/L Mg(C2H3O2)2·4H2O,0.1mmol/L 还原型谷胱甘肽,1% BSA,0.28mmol/L蔗糖;所述电脉冲仪参数为场强0.8kv/cm,电容3µF,2次电脉冲。所述电刺激时的卵子密度为11×104个/ml。本发明的方法简单有效,经电刺激诱导后,仿刺参的卵裂率可达到28%以上,胚胎存活率可达到98%以上。
4 ブラストイド、細胞株に基づく人工胚盤胞 JP2016508921 2014-04-16 JP2016518831A 2016-06-30 クレマン リヴロン,ニコラ; ブリッテルスワイク,クレメンス アントーニ ファン; ゲイセン,ニールス; ヤコブ フライ,エリック
本発明は、少なくとも1つの栄養芽細胞と少なくとも1つの多能性および/または全能性細胞とから2重層細胞凝集塊を形成し、当該細胞塊を培養し、人工胚盤胞を得ることによって、少なくとも2重層の細胞凝集塊および/もしくは人工胚盤胞、ならびに/またはブラストイドと称されるさらに発生したブラストイドを作製する方法に関する。この人工胚盤胞は、胞胚腔と内部細胞塊様組織とを囲む栄養外胚葉様組織を有する。細胞凝集塊は、栄養膜幹細胞と組み合わせて、全能性もしくは多能性幹細胞種、または人工多能性幹細胞種から形成することが可能である。ブラストイド形成は、好ましくは、Rho/ROCK抑制因子、Wnt経路調節因子、PKA経路調節因子、PKC経路調節因子、MAPK経路調節因子、STAT経路調節因子、Akt経路調節因子、Tgf経路調節因子およびHippo経路調節因子の1つ以上を含む培地中で細胞凝集塊を培養することによって行うことが可能である。本発明は、さらに、少なくとも2重層の細胞凝集塊を人工胚盤胞に成長させ、さらに発生したブラストイド、胎児または生存動物に成長させる方法に関する。本発明は、さらに、言及された化合物および/または細胞凝集塊を含む in vitro 細胞培養物に属する。
5 Method of improving the germline transfer efficiency of the primordial germ cells of birds JP2006500676 2004-04-21 JP2006514836A 2006-05-18 セチャン クォン; テソップ パク; ゼヨン ハン; ヨンホ ホン
本発明は、鳥類の始原生殖細胞の生殖系列転移効率の改善方法、これを用いた鳥類キメラ及び形質転換体の製造方法に関するものであって、さらに詳細には、(a)鳥類の胚子の始原生殖腺から始原生殖細胞(gonadal primordial germ cells, gPGCs)を分離する段階、及び(b)前記始原生殖細胞を少なくとも5日間インビトロ(in vitro)培養する段階を含む鳥類の始原生殖細胞の生殖系列転移効率の改善方法に関するものであって、本発明の方法は、gPGCsの生殖系列転移効率を改善するにおいて、その方法の実施が簡易でありながらも、それにより達成される生殖系列転移効率の改善の程度が非常に大きい。
6 Blastoid, cell line based artificial blastocyst US14784659 2014-04-16 US09822336B2 2017-11-21 Nicolas Clément Rivron; Clemens Antoni Van Blitterswijk; Niels Geijsen; Erik Jacob Vrij
A method for making an at least double layered cell aggregate and/or an artificial blastocyst, and/or a further-developed blastoid termed blastoid, by forming a double layered cell aggregate from at least one trophoblast cell and at least one pluripotent and/or totipotent cell, and culturing the aggregate to obtain an artificial blastocyst having a trophectoderm-like tissue that surrounds a blastocoel and an inner cell mass-like tissue. The cell aggregate can be formed from toti- or pluripotent stem cell types, or induced pluripotent stem cell types, in combination with trophoblast stem cells. Formation of a blastoid can be achieved by culturing the cell aggregate in a medium preferably comprising one or more of a Rho/ROCK inhibitor, a Wnt pathway modulator, a PKA pathway modulator, a PKC pathway modulator, a MAPK pathway modulator, a STAT pathway modulator, an Akt pathway modulator, a Tgf pathway modulator and a Hippo pathway modulator. Also, a method for growing an at least double layered cell aggregate into an artificial blastocyst, and into a further-developed blastoid, a foetus or a live animal and an in vitro cell culture comprising the mentioned compounds and/or cell aggregates.
7 Biological models capable of exhibiting secondary disease manifestations and useful for developing therapeutic drugs, diagnostic products and therapeutic or diagnostic procedures, methods of using same, and cells, tissues and organs derived therefrom US10042711 2001-12-12 US08012456B2 2011-09-06 Jennifer June Brown; Elazar Rabbani; James J. Donegan; Jayanta Roy-Chowdhury
This invention provides novel animal models for a human pathogen that is capable of exhibiting analogous secondary disease manifestation. Other animal models for a human pathogen are provided by this invention which are capable of exhibiting analogous secondary disease manifestations and are also capable of responding to therapeutic or preventive measures to such secondary disease manifestations. Other animal models for human retrovirus infections are provided including lower primates and primate excluding any members of the order Anthropoidea. Compositions, drugs, products and procedures for therapeutic and diagnostic applications derived from the animal models of this invention are also described and provided.
8 Methods for Assaying Gene Imprinting and Methylated CpG Islands US12350159 2009-01-07 US20100273658A1 2010-10-28 ANDREW P. FEINBERG; LIORA STRICHMAN-ALMASHANU; SHAN JIANG
Genomic imprinting is a parent of origin-dependent gene silencing that involves marking of alleles in the germline and differential expression in somatic cells of the offspring. Imprinted genes and abnormal imprinting have been implicated in development, human disease, and embryonic stem cell transplantation. We have established a model system for genomic imprinting using pluripotent 8.5 d.p.c. mouse embryonic germ (EG) cell lines derived from an interspecific cross. We find that allele-specific imprinted gene expression has been lost in these cells. However, partial restoration of allele-specific silencing can occur for some imprinted genes after in vitro differentiation of EG cells into somatic cell lineages, indicating the presence of a gametic memory that is separable from allele-specific gene silencing. We have also generated a library containing most methylated CpG islands. A subset of these clones was analyzed and revealed a subdivision of methylated CpG islands into 4 distinct subtypes: CpG islands belonging to high copy number repeat families; unique CpG islands methylated in all tissues; unique methylated CpG islands that are unmethylated in the paternal germline; and unique CpG islands methylated in tumors. This approach identifies a methylome of methylated CpG islands throughout the genome.
9 Gene imprinting and methylated CpG islands US11084085 2005-03-17 US07488815B2 2009-02-10 Andrew P. Feinberg; Liora Strichman-Almashanu; Shan Jiang
Genomic imprinting is a parent of origin-dependent gene silencing that involves marking of alleles in the germline and differential expression in somatic cells of the offspring. Imprinted genes and abnormal imprinting have been implicated in development, human disease, and embryonic stem cell transplantation. We have established a model system for genomic imprinting using pluripotent 8.5 d.p.c. mouse embryonic germ (EG) cell lines derived from an interspecific cross. We find that allele-specific imprinted gene expression has been lost in these cells. However, partial restoration of allele-specific silencing can occur for some imprinted genes after in vitro differentiation of EG cells into somatic cell lineages, indicating the presence of a gametic memory that is separable from allele-specific gene silencing. We have also generated a library containing most methylated CpG islands. A subset of these clones was analyzed and revealed a subdivision of methylated CpG islands into 4 distinct subtypes: CpG islands belonging to high copy number repeat families; unique CpG islands methylated in all tissues; unique methylated CpG islands that are unmethylated in the paternal germline; and unique CpG islands methylated in tumors. This approach identifies a methylome of methylated CpG islands throughout the genome.
10 Method for improving germline transmission efficiency of avian primordial germ cells US10554030 2004-04-21 US07476776B2 2009-01-13 Jae Yong Han; Tae Sub Park; Yeong Ho Hong; Se Chang Kwon
The present invention relates to a method for improving the germline transmission efficiency of avian primordial germ cells (PGCs), and methods for producing avian chimeras and transgenic using it. The present method comprises the steps of (a) isolating primordial germ cells (PGCs) from an avian embryonic gonad; and (b) culturing said PGCs in vitro for at least 5 days. According to the present method, the germline transmission efficiency of PGCs can be dramatically improved in a feasible manner.
11 Production of transgenic birds using stage X primordial germ cells US09992634 2001-11-14 US20030061629A1 2003-03-27 Pramod Sutrave
The present invention relates to methods for isolating primordial germ cells (PGCs) from the blastoderm of a stage X avian embryo. The present invention further relates to methods for producing a transgenic bird by modifying the isolated PGCs, such that the cells incorporate at least one transgene into their genetic material; transferring the modified PGCs into a suitable recipient, such as a blastoderm of an avian embryo, hatching the embryo; and testing for the presence of the transgene or expression of the protein encoded by the transgene.
12 Transgenic animal model for neurodegenerative disorders US09687731 2000-10-13 US06504080B1 2003-01-07 Petrus Herman Maria Van Der Putten
Animal model useful for testing potential therapeutic agents for the treatment of neurodegenerative disorders, in particular disorders associated with the presence of Lewy pathology.
13 Extended human hematopoiesis in a heterologous host US836195 1992-02-13 US6093872A 2000-07-25 Hideto Kaneshima; Reiko Namikawa; Joseph McCrary McCune
A human hematopoietic system is provided in an immunocompromised mammalian host, where the hematopoietic system is functional for extended periods of time. Particularly, human fetal liver tissue and human fetal thymus is introduced into an appropriate site of a young immunocompromised mouse at a site supplied with a vascular system, whereby the fetal tissue results in novel formation of functional human bone marrow tissue.
14 Chimeric immunocompromised mammal comprosing vascularized fetal organ tissue US205053 1994-03-01 US5639939A 1997-06-17 Joseph M. McCune, III
Xenogeneic tissue is introduced into an immunocompromised host for interacting with agents and using such interaction for evaluating efficacy of drugs and vaccines, producing xenogeneic monoclonal antibodies, evaluating the effect of the various agents on specific tissues and the like. Particularly, drugs can be evaluated for their efficacy against a wide variety of pathogens which infect xenogeneic tissue, agents can be evaluated for their effect on the xenogeneic immune system and monoclonal antibodies to a predetermined epitope may be produced.
15 Extended human hematopoiesis in a heterologous host US434706 1995-05-04 US5625127A 1997-04-29 Hideto Kaneshima; Reiko Namikawa; Joseph M. McCune
A human hematopoietic system is provided in an immunocompromised mammalian host, where the hematopoietic system is functional for extended periods of time. Particularly, human fetal liver tissue and human fetal thymus is introduced into an appropriate site of a young immunocompromised mouse at a site supplied with a vascular system, whereby the fetal tissue results in novel formation of functional human bone marrow tissue.
16 標的化された遺伝子修飾のための方法及び組成物、並びに使用方法 JP2016575039 2015-06-26 JP2017518758A 2017-07-13 デイビッド フレンドウェイ,; グスタボ ドロゲット,; アントニー ガグリアルディ,; 淳子 久野; ボイテック オーバッハ,; デイビッド エム. バレンズエラ,
Y染色体又は困難な標的遺伝子座上で標的化された遺伝子修飾を発生させるための方法及び組成物が提供される。組成物は、Sryタンパク質のレベル及び/又は活性を減少させる修飾を有するXY多能性及び/又は全能性動物細胞(すなわち、XY ES細胞又はXY iPS細胞)を含むインビトロ培養物を含み、XY F0の繁殖のある雌の発達を促進する培地中でこれらの細胞を培養する。そのような組成物は、F0世代における繁殖力のある雌XY非ヒト哺乳動物を作製するための様々な方法での用途を見出す。
17 Outbred embryonic stem cells with a good developmental potential JP2006517921 2004-07-08 JP2007533291A 2007-11-22 アラン クラーク ピーターソン
本発明は、少なくとも2つの異なるマウス系統由来の対立遺伝子を含み、高い発生能を有する非近交系マウス胚性幹(ES)細胞を提供する。 ES細胞は、場合により導入遺伝子のための導入部位を含む。 また、ES細胞の作製方法も開示する。 さらに、本発明は、非近交系ES細胞由来のキメラマウスおよびトランスジェニックマウス、ならびにそのようなマウスの作製方法を提供する。
18 Chimeric non-human animals and their use JP32378888 1988-12-23 JP2801228B2 1998-09-21 マックラリー マッキューン ジョージフ
19 Chimeric immune defenseless state animals and their use JP32378888 1988-12-23 JPH0231632A 1990-02-01 JIYOOJIFU MATSUKURARII MATSUKI
PURPOSE: To acquire chimeric immune defenseless state animals by forming immunodeficient animal recipients which lack functional syngenic lymphocytes for the reasons exclusive of the deletion of the functional thymus and include at least a part of immune systems. CONSTITUTION: Plasma cells or the precursors thereof are isolated from the immunodeficient mouse recipients subjected to chimeric conjugation and, thereafter, the isolated cells or precursors are made immortal and the cells made immortal are subjected to screening to produce human immunoglobulin. The recipients described above are hetratrans cells, ≥1 organs and second organs. One or more organs include the functional thymuses. The transplantation cells include at least one hematopoietic stem cells, immature differentiated hematopoietic cells or matured differentiated hematopoietic cells. COPYRIGHT: (C)1990,JPO
20 Method of improving the germline transfer efficiency of the primordial germ cells of birds JP2006500676 2004-04-21 JP4343946B2 2009-10-14 セチャン クォン; テソップ パク; ゼヨン ハン; ヨンホ ホン
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