Engraftment and tumor formation after allogeneic in utero transplantation of primate embryonic stem cells1

Asano, Takayuki; Ageyama, Naohide; Takeuchi, Koichi; Momoeda, Mikio; Kitano, Yoshihiro; Sasaki, Keiko; Ueda, Yasuji; Suzuki, Yutaka; Kondo, Yasushi; Torii, Ryuzo; Hasegawa, Mamoru; Ookawara, Shigeo; Harii, Kiyonori; Terao, Keiji; Ozawa, Keiya; Hanazono, Yutaka

doi:10.1097/01.tp.0000090342.85649.81

Cited by 52 publications

(31 citation statements)

References 27 publications

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“…Accordingly, several groups are examining hematopoietic development from nonhuman primate ES cells. [184][185][186][187][188] In general, these lines exhibit hematopoiesis similar to what is observed from human ES cells. While these studies are relatively preliminary, continued investigation of nonhuman primate ES cells will provide improved preclinical models for ES cell-derived hematopoietic transplantation therapies.…”

Section: The Futurementioning

confidence: 69%

Designer blood: creating hematopoietic lineages from embryonic stem cells

Olsen

Stachura

Weiss

2006

Blood

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Section: The Futurementioning

confidence: 69%

Designer blood: creating hematopoietic lineages from embryonic stem cells

Olsen

Stachura

Weiss

2006

Blood

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“…Whereas questions of optimized expansion, specific in vitro differentiation, and purification of ESCderived CMs prior to transplantation can be addressed directly by using hESCs [9,11,13], other issues such as postimplantation functionality, ESC transplantation-related immunological processes [29,30], or formation of teratoma [31] have to be investigated in allogeneic large animal models prior to clinical use. According to the (still very limited) available data, one can expect rESCs to be very similar to hESCs in many aspects, including expression of marker genes, pluripotency, proliferation potential, differentiation potential, and genetic stability [32].…”

Section: Discussionmentioning

confidence: 99%

Generation and Characterization of Functional Cardiomyocytes from Rhesus Monkey Embryonic Stem Cells

et al. 2006

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Embryonic stem cells (ESCs) from mice and humans (hESCs) have been shown to be able to efficiently differentiate toward cardiomyocytes (CMs). Because murineESCs and hESCs do not allow for establishment of preclinical allogeneic transplantation models, the aim of our study was to generate functional CMs from rhesus monkey ESCs (rESCs). Although formation of ectodermal and neuronal/glial cells appears to be the default pathway of the rESC line R366.4, we were able to change this commitment and to direct generation of endodermal/mesodermal cells and further differentiation toward CMs. Differentiation of rESCs resulted in an average of 18% of spontaneously contracting embryoid bodies (EBs) from rESCs. Semiquantitative reverse transcription-polymerase chain reaction analyses demonstrated expression of marker genes typical for endoderm, mesoderm, cardiac mesoderm, and CMs, including brachyury, goosecoid, Tbx-5, Tbx-20, Mesp1, Nkx2.5, GATA-4, FOG-2, Mlc2a, MLC2v, ANF, and ␣-MHC in rESC-derived CMs. Immunohistological and ultrastructural studies showed expression of CM-typical proteins, including sarcomeric actinin, troponin T, titin, connexin 43, and cross-striated muscle fibrils. Electrophysiological studies by means of multielectrode arrays revealed evidence of functionality, electrical coupling, and ␤-adrenergic signaling of the generated CMs. This is the first study demonstrating generation of functional CMs derived from rESCs. In contrast to hESCs, rESCs allow for establishment of preclinical allogeneic transplantation models. Moreover, rESC-derived CMs represent a cell source for the development of high-throughput assays for cardiac safety pharmacology.

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“…Indeed, the full developmental potential of ES cells can best be determined by measuring their ability to contribute to embryonic, fetal, and adult cell lineages in chimeric animals. Initial successes have been reported following in utero transplantation of peripheral blood stem cells [14] or embryonic stem cells [15]. We have established that membrane-labeled ES cells, when injected into four-or eight-cell-stage embryos, propagate and integrate into the blastocyst as a first step in producing chimeric rhesus monkeys [16].…”

Section: Isolation and Characterizationmentioning

confidence: 99%

Progress with Nonhuman Primate Embryonic Stem Cells1

Wolf

Kuo

Pau

et al. 2004

Biology of Reproduction

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Embryonic stem cells hold potential in the fields of regenerative medicine, developmental biology, tissue regeneration, disease pathogenicity, and drug discovery. Embryonic stem (ES) cell lines are now available in primates, including man, rhesus, and cynomologous monkeys. Monkey ES cells serve as invaluable clinically relevant models for studies that can't be conducted in humans because of practical or ethical limitations, or in rodents because of differences in physiology and anatomy. Here, we review the current status of nonhuman primate research with ES cells, beginning with a description of their isolation, characterization, and availability. Substantial limitations still plague the use of primate ES cells, such as their required growth on feeder layers, poor cloning efficiency, and restricted availability. The ability to produce homogenous populations of both undifferentiated as well as differentiated phenotypes is an important challenge, and genetic approaches to achieving these objectives are discussed. Finally, safety, efficiency, and feasibility issues relating to the transplantation of ES-derived cells are considered.

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Engraftment and tumor formation after allogeneic in utero transplantation of primate embryonic stem cells1

Abstract: Transplanted cynomolgus ES cells can be engrafted in allogeneic fetuses. The cells will, however, form a tumor if they "leak" into an improper space such as the thoracic cavity.

Cited by 52 publications

References 27 publications

Designer blood: creating hematopoietic lineages from embryonic stem cells

Designer blood: creating hematopoietic lineages from embryonic stem cells

Generation and Characterization of Functional Cardiomyocytes from Rhesus Monkey Embryonic Stem Cells

Progress with Nonhuman Primate Embryonic Stem Cells1

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