公开(公告)号：US06235970B1

公开(公告)日：2001-05-22

申请号：US08935052

申请日：1997-09-22

Applicant: Steven L. Stice ,  Jose Cibelli ,  James Robl ,  Paul Golueke ,  F. Abel Ponce de Leon ,  D. Joseph Jerry

Inventor： Steven L. Stice ,  Jose Cibelli ,  James Robl ,  Paul Golueke ,  F. Abel Ponce de Leon ,  D. Joseph Jerry

IPC: C12N1500

CPC classification number: A01K67/0275 ,  A01K67/027 ,  A01K2217/05 ,  A01K2227/101 ,  A01K2227/106 ,  A61K35/12 ,  C12N5/0603 ,  C12N15/8771 ,  C12N15/8778 ,  C12N2510/00 ,  C12N2517/02 ,  C12N2517/04

Abstract: An improved method of nuclear transfer involving the transplantation of donor differentiated cell nuclei into enucleated oocytes of the same species as the donor cell is provided. The resultant nuclear transfer units are useful for multiplication of genotypes and transgenic genotypes by the production of fetuses and offspring, and for production of isogenic CICM cells, including human isogenic embryonic or stem cells. Production of genetically engineered or transgenic mammalian embryos, fetuses and offspring is facilitated by the present method since the differentiated cell source of the donor nuclei can be genetically modified and clonally propagated.

Abstract translation: 提供了涉及将供体分化的细胞核移植到与供体细胞相同物种的去核卵母细胞中的改进的核转移方法。 所产生的核转移单位可用于通过胎儿和后代的产生以及用于产生包括人同种异体胚胎或干细胞在内的等基因CICM细胞的基因型和转基因基因型的倍增。 通过本方法促进遗传工程或转基因哺乳动物胚胎，胎儿和后代的生产，因为供体核的分化细胞源可以被遗传修饰和克隆繁殖。

公开(公告)号：US5843754A

公开(公告)日：1998-12-01

申请号：US473794

申请日：1995-06-06

Applicant: Joan L. Susko-Parrish ,  David L. Northey ,  M. Lorraine Leibfried-Rutledge ,  Steven L. Stice

Inventor： Joan L. Susko-Parrish ,  David L. Northey ,  M. Lorraine Leibfried-Rutledge ,  Steven L. Stice

IPC: C12N5/075 ,  C12N15/873 ,  C12N5/00

CPC classification number: C12N15/873 ,  C12N5/0609 ,  C12N2500/14 ,  C12N2501/70 ,  C12N2501/999

Abstract: A process of parthenogenic activation of mammalian oocytes which includes increasing intercellular levels of divalent cations in the oocyte; and reducing phosphorylation of cellular proteins in the oocyte. One method of accomplishing this is by introducing Ca.sup.2+ free cation, such as ionomycin, to the oocyte and then preventing phosphorylation of the cellular proteins within the oocyte by adding a serine-threonine kinase inhibitor, such as 6-dimethylaminopurine (DMAP).

Abstract translation: 哺乳动物卵母细胞的单性激活过程，其包括增加卵母细胞中二价阳离子的细胞间水平; 并减少卵母细胞中细胞蛋白的磷酸化。 实现这一点的一个方法是通过将Ca 2+游离的阳离子（如离子霉素）引入卵母细胞，然后通过加入丝氨酸 - 苏氨酸激酶抑制剂如6-二甲基氨基嘌呤（DMAP）来防止卵母细胞内的细胞蛋白的磷酸化。

公开(公告)号：US20150320833A1

公开(公告)日：2015-11-12

申请号：US14651895

申请日：2013-12-13

Applicant: Steven L. STICE ,  John F. PERONI ,  Jennifer MUMAW ,  UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.

Inventor： Steven L. STICE ,  John F. PERONI ,  Jennifer MUMAW

IPC: A61K38/18 ,  A61K45/06 ,  A61K9/16 ,  A61K35/28

CPC classification number: A61K38/1875 ,  A61K9/0019 ,  A61K9/06 ,  A61K9/1641 ,  A61K35/28 ,  A61K38/1866 ,  A61K38/195 ,  A61K38/204 ,  A61K38/2053 ,  A61K45/06 ,  A61K48/00 ,  A61L27/18 ,  A61L27/3834 ,  A61L27/54 ,  A61L2300/64 ,  A61L2400/06 ,  A61L2430/02 ,  C12N15/86 ,  C12N2710/10343 ,  C12N2710/10371 ,  C12N2740/15043 ,  C12N2740/15071 ,  C12N2750/14143 ,  A61K2300/00 ,  C08L71/02

Abstract: Mesenchymal stem cells (MSCs) and uses thereof are provided. MSCs for inducing ossification and enhancing bone and/qr cartilage repair in a patient in need thereof are also provided. The method and compositions combine MSCs, at least one bone regeneration protein, such as bone morphogenetic protein (e.g. BMP-2), optionally in combination with additional cell growth factors including the components of a cell growth medium, further in combination with a biomaterial for delivery of the cells to the repair site in the patient are also provided.

Abstract translation: 提供间充质干细胞（MSC）及其用途。 还提供了用于在有需要的患者中诱导骨化和增强骨和/或软骨修复的MSC。 所述方法和组合物将MSC，至少一种骨再生蛋白（例如骨形态发生蛋白（例如BMP-2））组合，任选与另外的细胞生长因子（包括细胞生长培养基的组分）组合，进一步与生物材料组合 还提供了将细胞递送到患者的修复部位。

公开(公告)号：US07291764B1

公开(公告)日：2007-11-06

申请号：US09394902

申请日：1999-09-13

Applicant: Steven L. Stice ,  Jose Cibelli ,  James Robl ,  Paul Golueke

Inventor： Steven L. Stice ,  Jose Cibelli ,  James Robl ,  Paul Golueke

IPC: C12N15/00 ,  C12N5/00 ,  A01K67/00

CPC classification number: C12N15/8778

Abstract: An improved method of nuclear transfer involving the transplantation of donor differentiated pig cell nuclei into enucleated pig oocytes is provided. The resultant nuclear transfer units are useful for multiplication of genotypes and transgenic genotypes by the production of fetuses and offspring. Production of genetically engineered or transgenic pig embryos, fetuses and offspring is facilitated by the present method since the differentiated cell source of the donor nuclei can be genetically modified and clonally propagated.

Abstract translation: 提供了涉及将供体分化的猪细胞核移植到去核猪卵母细胞中的改进的核转移方法。 所产生的核转移单位可用于通过胎儿和后代的产生来增殖基因型和转基因基因型。 通过本发明的方法促进转基因植物或转基因猪胚胎，胎儿和后代的生产，因为供体核的分化细胞源可被遗传修饰和克隆繁殖。

公开(公告)号：US06235969B1

公开(公告)日：2001-05-22

申请号：US08888057

申请日：1997-07-03

Applicant: Steven L. Stice ,  James M. Robl ,  Jose Cibelli ,  Paul Golueke

Inventor： Steven L. Stice ,  James M. Robl ,  Jose Cibelli ,  Paul Golueke

IPC: C12N1500

CPC classification number: C12N15/8778 ,  A01K67/027 ,  A01K67/0273 ,  A01K67/0275 ,  A01K2217/05 ,  A01K2227/101 ,  A61K35/12 ,  A61K38/00 ,  C12N5/0603 ,  C12N15/8771 ,  C12N2510/00 ,  C12N2517/02 ,  C12N2517/04

Abstract: An improved method of nuclear transfer involving the transplantation of donor differentiated pig cell nuclei into enucleated pig oocytes is provided. The resultant nuclear transfer units are useful for multiplication of genotypes and transgenic genotypes by the production of fetuses and offspring. Production of genetically engineered or transgenic pig embryos, fetuses and offspring is facilitated by the present method since the differentiated cell source of the donor nuclei can be genetically modified and clonally propagated.

Abstract translation: 提供了涉及将供体分化的猪细胞核移植到去核猪卵母细胞中的改进的核转移方法。 所产生的核转移单位可用于通过胎儿和后代的产生来增殖基因型和转基因基因型。 通过本发明的方法促进转基因植物或转基因猪胚胎，胎儿和后代的生产，因为供体核的分化细胞源可被遗传修饰和克隆繁殖。

公开(公告)号：US06194202B1

公开(公告)日：2001-02-27

申请号：US08610744

申请日：1996-03-04

Applicant: Joan L. Susko-Parrish ,  David L. Northey ,  M. Lorraine Leibfried-Rutledge ,  Steven L. Stice

Inventor： Joan L. Susko-Parrish ,  David L. Northey ,  M. Lorraine Leibfried-Rutledge ,  Steven L. Stice

IPC: C12N506

CPC classification number: C12N15/873 ,  C12N5/0609 ,  C12N2500/14 ,  C12N2501/70 ,  C12N2501/999

Abstract: A process of parthenogenic activation of mammalian oocytes which includes increasing intracellular levels of divalent cations in the oocyte; and reducing phosphorylation of cellular proteins in the oocyte. One method of accomplishing this is by introducing Ca2+ free cation, such as ionomycin, to the oocyte and then preventing phosphorylation of the cellular proteins within the oocyte by adding a serine-threonine kinase inhibitor, such as 6-dimethylaminopurine (DMAP).

Abstract translation: 哺乳动物卵母细胞的单性激活过程，其包括增加卵母细胞中二价阳离子的细胞内水平; 并减少卵母细胞中细胞蛋白的磷酸化。 实现这一点的一个方法是通过将Ca 2+游离的阳离子（如离子霉素）引入卵母细胞，然后通过加入丝氨酸 - 苏氨酸激酶抑制剂如6-二甲基氨基嘌呤（DMAP）来防止卵母细胞内的细胞蛋白的磷酸化。

公开(公告)号：US20110277049A1

公开(公告)日：2011-11-10

申请号：US13188286

申请日：2011-07-21

Applicant: Steven L. Stice ,  John Gibbons ,  Donald Respess

Inventor： Steven L. Stice ,  John Gibbons ,  Donald Respess

IPC: A01K67/02

CPC classification number: C12N15/8771

Abstract: Genetic material is derived from animals post-mortem, and used in nuclear transfer processes to produce cloned embryos and live cloned animals having genetic make-ups identical to the post mortem animals. The method has particular applicability to the management and breeding of livestock, to the production of animals having desired genetic traits, and to the integration of those genetic traits into selective breeding operations.

Abstract translation: 遗传物质来源于宰后动物，并用于核转移过程中，以产生具有与死后动物相同的遗传构成的克隆胚胎和活的克隆动物。 该方法特别适用于牲畜的管理和育种，具有所需遗传性状的动物的生产，以及将这些遗传性状整合到选育育种操作中。

公开(公告)号：US6077710A

公开(公告)日：2000-06-20

申请号：US176395

申请日：1998-10-21

Applicant: Joan L. Susko-Parrish ,  David L. Northey ,  M. Lorraine Leibfried-Rutledge ,  Steven L. Stice

Inventor： Joan L. Susko-Parrish ,  David L. Northey ,  M. Lorraine Leibfried-Rutledge ,  Steven L. Stice

IPC: C12N5/075 ,  C12N15/873 ,  C12N5/06

CPC classification number: C12N15/873 ,  C12N5/0609 ,  C12N2500/14 ,  C12N2501/70 ,  C12N2501/999

Abstract: A process of parthenogenic activation of mammalian oocytes which includes increasing intracellular levels of divalent cations in the oocyte; and reducing phosphorylation of cellular proteins in the oocyte. One method of accomplishing this is by introducing Ca.sup.2+ free cation, such as ionomycin, to the oocyte and then preventing phosphorylation of the cellular proteins within the oocyte by adding a serine-threonine kinase inhibitor, such as 6-dimethylaminopurine (DMAP).

Abstract translation: 哺乳动物卵母细胞的单性激活过程，其包括增加卵母细胞中二价阳离子的细胞内水平; 并减少卵母细胞中细胞蛋白的磷酸化。 实现这一点的一个方法是通过将Ca 2+游离的阳离子（如离子霉素）引入卵母细胞，然后通过加入丝氨酸 - 苏氨酸激酶抑制剂如6-二甲基氨基嘌呤（DMAP）来防止卵母细胞内的细胞蛋白的磷酸化。

公开(公告)号：US5905042A

公开(公告)日：1999-05-18

申请号：US626054

申请日：1996-04-01

Applicant: Steven L. Stice ,  Paul J. Golueke

Inventor： Steven L. Stice ,  Paul J. Golueke

IPC: C12N15/09 ,  A01K67/027 ,  C12N5/073 ,  C12N5/0735 ,  C12N5/10 ,  C12N15/877 ,  C12N5/06 ,  C12N15/85 ,  C12N15/86

CPC classification number: A01K67/0275 ,  C12N15/8771 ,  C12N5/0603 ,  C12N5/0606 ,  A01K2217/05 ,  C12N2501/235 ,  C12N2502/13 ,  C12N2510/00

Abstract: Novel cultured inner cell mass (CICM) cells, and cell lines, derived from ungulates, in particular, pigs and cows, and methods for their preparation are provided. The subject CICMs possess similar morphology and express cell markers identically or substantially similarly to ICMs of undifferentiated developing embryos for prolonged culturing periods. Heterologous DNAs may be introduced into the subject CICM cells and cell lines to produce transgenic cells useful for the production of transgenic embryos, fetuses and/or offspring, e.g., by nuclear transfer procedures.

Abstract translation: 提供了新颖的培养的内细胞团（CICM）细胞和源自有蹄类动物，特别是猪和牛的细胞系及其制备方法。 受试者CICM具有与未分化发育的胚胎的ICM相似或基本上类似于延长培养期的相似形态和表达细胞标记。 可以将异源DNA引入受试者CICM细胞和细胞系以产生用于生产转基因胚胎，胎儿和/或后代的转基因细胞，例如通过核转移程序。

公开(公告)号：US06680199B1

公开(公告)日：2004-01-20

申请号：US09576592

申请日：2000-05-22

Applicant: Joan L. Susko-Parrish ,  David L. Northey ,  M. Lorraine Leibfried-Rutledge ,  Steven L. Stice

Inventor： Joan L. Susko-Parrish ,  David L. Northey ,  M. Lorraine Leibfried-Rutledge ,  Steven L. Stice

IPC: C12N500

CPC classification number: C12N15/873 ,  C12N5/0609 ,  C12N2500/14 ,  C12N2501/70 ,  C12N2501/999

Abstract: A process of parthenogenic activation of mammalian oocytes which includes increasing intercellular levels of divalent cations in the oocyte; and reducing phosphorylation of cellular proteins in the oocyte. One method of accomplishing this is by introducing Ca2+free cation, such as ionomycin, to the oocyte and then preventing phosphorylation of the cellular proteins within the oocyte by adding a serine-threonine kinase inhibitor, such as 6-dimethylaminopurine (DMAP).

Abstract translation: 哺乳动物卵母细胞的单性激活过程，其包括增加卵母细胞中二价阳离子的细胞间水平; 并减少卵母细胞中细胞蛋白的磷酸化。 实现这一点的一个方法是通过向卵母细胞中引入Ca 2+游离阳离子，例如离子霉素，然后通过加入丝氨酸 - 苏氨酸激酶抑制剂（例如6-二甲基氨基嘌呤（DMAP））来防止卵母细胞内的细胞蛋白的磷酸化 ）。