Derivation of pluripotent stem cells from cultured human primordial germ cells

Shamblott, Michael J.; Axelman, Joyce; Wang, Shunping; Bugg, Elizabeth M.; Littlefield, John W.; Donovan, Peter; Blumenthal, Paul D.; Huggins, George R.; Gearhart, John D.

doi:10.1073/pnas.95.23.13726

Cited by 1,273 publications

(535 citation statements)

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“…Human pluripotent stem cells have been generated from cells isolated from the inner cell mass of the blastocyst (embryonic stem cells), primordial gonadal ridge (embryonic germ cells), and somatic cells (induced pluripotent stem cells) [1][2][3][4]. These pluripotent stem cells have the capability to proliferate and self-renew over long periods of time and to differentiate toward almost all cell types.…”

Section: Introductionmentioning

confidence: 99%

Engineering Musculoskeletal Tissues with Human Embryonic Germ Cell Derivatives

et al. 2010

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The cells derived from differentiating embryoid bodies of human embryonic germ (hEG) cells express a broad spectrum of gene markers and have been induced toward ectoand endodermal lineages. We describe here in vitro and in vivo differentiation of hEG-derived cells (LVEC line) toward mesenchymal tissues. The LVEC cells express many surface marker proteins characteristic of mesenchymal stem cells and differentiated into cartilage, bone, and fat. Homogenous hyaline cartilage was generated from cells after 63 population doublings. In vivo results demonstrate cell survival, differentiation, and tissue formation. The high proliferative capacity of hEG-derived cells and their ability to differentiate and form three-dimensional mesenchymal tissues without teratoma formation underscores their significant potential for regenerative medicine. The adopted coculture system also provides new insights into how a microenvironment comprised of extracellular and cellular components may be harnessed to generate hierarchically complex tissues from pluripotent cells. STEM CELLS 2010;28:765-774 Disclosure of potential conflicts of interest is found at the end of this article.

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Section: Introductionmentioning

confidence: 99%

Engineering Musculoskeletal Tissues with Human Embryonic Germ Cell Derivatives

et al. 2010

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“…Stage‐specific embryonal antigens are known and established as markers for murine as well as human embryonic stem (ES) cells 14, 15, 16. Given the observed similarities of gene expression profiles of murine as well as human basal PESCs with the profiles of ES cells 11, we were interested in the specific expression of SSEAs we discovered in the cell surface protein screen.…”

Section: Resultsmentioning

confidence: 99%

Protein profile of basal prostate epithelial progenitor cells—stage‐specific embryonal antigen 4 expressing cells have enhanced regenerative potential in vivo

Höfner

Klein

Eisen

et al. 2016

J Cellular Molecular Medi

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The long‐term propagation of basal prostate progenitor cells ex vivo has been very difficult in the past. The development of novel methods to expand prostate progenitor cells in vitro allows determining their cell surface phenotype in greater detail. Mouse (Lin−Sca‐1+ CD49f+ Trop2high‐phenotype) and human (Lin− CD49f+ TROP2high) basal prostate progenitor cells were expanded in vitro. Human and mouse cells were screened using 242 anti‐human or 176 antimouse monoclonal antibodies recognizing the cell surface protein profile. Quantitative expression was evaluated at the single‐cell level using flow cytometry. Differentially expressed cell surface proteins were evaluated in conjunction with the known CD49f+/TROP2high phenotype of basal prostate progenitor cells and characterized by in vivo sandwich‐transplantation experiments using nude mice. The phenotype of basal prostate progenitor cells was determined as CD9+/CD24+/CD29+/CD44+/CD47+/CD49f+/CD104+/CD147+/CD326+/Trop2high of mouse as well as human origin. Our analysis revealed several proteins, such as CD13, Syndecan‐1 and stage‐specific embryonal antigens (SSEAs), as being differentially expressed on murine and human CD49f+ TROP2+ basal prostate progenitor cells. Transplantation experiments suggest that CD49f+ TROP2high SSEA‐4high human prostate basal progenitor cells to be more potent to regenerate prostate tubules in vivo as compared with CD49f+ TROP2high or CD49f+ TROP2high SSEA‐4low cells. Determination of the cell surface protein profile of functionally defined murine and human basal prostate progenitor cells reveals differentially expressed proteins that may change the potency and regenerative function of epithelial progenitor cells within the prostate. SSEA‐4 is a candidate cell surface marker that putatively enables a more accurate identification of the basal PESC lineage.

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“…They exhibit telomerase activity, which is consistent with their extended capability for self-renewal (Liu, 2000;Pera et al, 2000;Lin et al, 2003). When released from inhibitory control in vitro, these cells will spontaneously differentiate into and exhibit phenotypic expression markers for cells of ectodermal, mesodermal, and endodermal origin (Thomson et al, 1995(Thomson et al, , 1998Shamblott et al, 1998;Pera et al, 2000). Thus, embryonic stem cells exhibit pluripotentiality, i.e., the ability of a single cell to form multiple types of tissue from all three primary germ layer lineages.…”

mentioning

confidence: 80%

“…They have been isolated from the blastocyst, inner cell mass, and gonadal ridges of rodents and primates, including humans (Evans and Kaufman, 1981;Martin, 1981;Thomson et al, 1995Thomson et al, , 1998Shamblott et al, 1998;Pera et al, 2000). After isolation and growth in vitro with inhibitory agents (i.e., leukemia inhibitory factor, ESGRO, and/or fibroblast feeder layers), these cells exhibit immunological and molecular markers for undifferentiated embryonic cells (Niwa et al, 2000;Pera et al, 2000;Pesce and Scholer, 2001;Henderson et al, 2002;Cheng et al, 2003).…”

mentioning

confidence: 99%

“…Thus, embryonic stem cells exhibit pluripotentiality, i.e., the ability of a single cell to form multiple types of tissue from all three primary germ layer lineages. Based on the unique qualities of extended capability for self-renewal and pluripotentiality, embryonic stem cells have been proposed as a source of donor cells for tissue transplantation (Thomson et al, 1995(Thomson et al, , 1998Shamblott et al, 1998;Assady et al, 2001;Lumelsky et al, 2001). Unfortunately, transplantation of undifferentiated embryonic stem cells in vivo has resulted thus far in the formation of teratomas (Thomson et al, 1995(Thomson et al, , 1998Shamblott et al, 1998;Pera et al, 2000).…”

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confidence: 99%

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Clonogenic analysis reveals reserve stem cells in postnatal mammals. II. Pluripotent epiblastic‐like stem cells

et al. 2004

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Undifferentiated cells have been identified in the prenatal blastocyst, inner cell mass, and gonadal ridges of rodents and primates, including humans. After isolation these cells express molecular and immunological markers for embryonic cells, capabilities for extended self‐renewal, and telomerase activity. When allowed to differentiate, embryonic stem cells express phenotypic markers for tissues of ectodermal, mesodermal, and endodermal origin. When implanted in vivo, undifferentiated noninduced embryonic stem cells formed teratomas. In this report we describe a cell clone isolated from postnatal rat skeletal muscle and derived by repetitive single‐cell clonogenic analysis. In the undifferentiated state it consists of very small cells having a high ratio of nucleus to cytoplasm. The clone expresses molecular and immunological markers for embryonic stem cells. It exhibits telomerase activity, which is consistent with its extended capability for self‐renewal. When induced to differentiate, it expressed phenotypic markers for tissues of ectodermal, mesodermal, and endodermal origin. The clone was designated as a postnatal pluripotent epiblastic‐like stem cell (PPELSC). The undifferentiated clone was transfected with a genomic marker and assayed for alterations in stem cell characteristics. No alterations were noted. The labeled clone, when implanted into heart after injury, incorporated into myocardial tissues undergoing repair. The labeled clone was subjected to directed lineage induction in vitro, resulting in the formation of islet‐like structures (ILSs) that secreted insulin in response to a glucose challenge. This study suggests that embryonic‐like stem cells are retained within postnatal mammals and have the potential for use in gene therapy and tissue engineering. Anat Rec Part A 277A:178–203, 2004. © 2004 Wiley‐Liss, Inc.

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Derivation of pluripotent stem cells from cultured human primordial germ cells

Abstract: ABSTRACT

Cited by 1,273 publications

References 37 publications

Engineering Musculoskeletal Tissues with Human Embryonic Germ Cell Derivatives

Engineering Musculoskeletal Tissues with Human Embryonic Germ Cell Derivatives

Protein profile of basal prostate epithelial progenitor cells—stage‐specific embryonal antigen 4 expressing cells have enhanced regenerative potential in vivo

Clonogenic analysis reveals reserve stem cells in postnatal mammals. II. Pluripotent epiblastic‐like stem cells

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