Rhythmus: Eine Begriffsbestimmung

Stevens, Jane R.; Seidel, Wilhelm

doi:10.2307/843497

Cited by 3 publications

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“…This would not be surprising, in view of the experimental origin of the teratoma from a 6-day postimplantation embryo (7). Moreover, the tumor stem cells have been found to resemble certain undifferentiated cells of the early postimplantation stage, rather than preimplantation-stage cells, in their ultrastructure (19) and alkaline phosphatase content (20); their soluble protein profiles also differ from those of morula cells (5).…”

Section: Resultsmentioning

confidence: 99%

“…The OTT 6050 teratoma was experimentally produced by Stevens in 1967 (7), by grafting a 6-day chromosomally male (X/Y) embryo (8) of the 129/Sv slJ C P inbred strain (to be referred to as 129) under the testis capsule. The embryo became disorganized and formed a teratoma which, after intraperitoneal injection into another recipient, was converted to a modified ascites form.…”

Section: Methodsmentioning

confidence: 99%

“…We therefore undertook experiments in which mouse teratocarcinoma cells were injected into the cavity of genetically marked blastocysts (5,6). The donor cells were from the "cores" of teratoma embryoid bodies grown only in vvo as a transplantable ascites since the tumor (OTT 6050) was isolated in 1967 (7). This source seemed particularly promising because the cells had reAbbreviations: GPI, glucosephosphate isomerase; IDH, isocitrate dehydrogenase.…”

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confidence: 99%

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Totipotency and normal differentiation of single teratocarcinoma cells cloned by injection into blastocysts.

Illmensee¹,

Mintz²

1976

Proc. Natl. Acad. Sci. U.S.A.

398

169

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A definitive test for developmental totipotency of mouse malignant teratocarcinoma cells was conducted by cloning singly injected cells in genetically marked blastocysts. Totipotency was conclusively shown in an adult mosaic female whose tumor-strain cells had made substantial contributions to all of the wide range of its somatic tissues analyzed; the clonally propagated cell lineage had therefore differentiated in numerous normal directions. The test cells were from "cores" of embryoid bodies of a euploid, chromosomally male (X/Y), ascites tumor grown only in vivo by transplantation for 8 years. The capacity of cells from the same source to differentiate, in a phenotypic male, into reproductively functional sperms, has been shown in our previous experiments [(1975) Proc. Nat. Acad. Sci. USA 72, 3585-3589]. Cells from this transplant line therefore provide material suitable for projected somatic and germ-line genetic analyses of mammalian differentiation based on "cycling" of mutation-carrying tumor cells through developing embryos. In some animals obtained from single-cell injections tumor-derived cells were sporadically distributed in developmentally unrelated tissues. These cases can be accounted for by delayed and haphazard cellular integration, and by a marked degree of sustained cellular developmental flexibility in early mammalian development, irrespective of certain classical "germ-layer" designations. All mosaic mice obtained have thus far been free of teratomas. In one case, the injected stem cell contributed only to the pancreas and gave rise to a malignancy resembling pancreatic adenocarcinoma. The high modal frequency of euploidy in these individually tested cells thus tends to indicate that a near-normal chromosome complement is sufficient for total restoration of orderly gene expression in a normal embryonic environment; it may also be necessary for teratoma stem-cell proliferation to be terminated there.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Totipotency and normal differentiation of single teratocarcinoma cells cloned by injection into blastocysts.

Illmensee¹,

Mintz²

1976

Proc. Natl. Acad. Sci. U.S.A.

398

169

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“…Some teratomas have been experimentally converted to a modified ascites form, termed "embryoid bodies" (3). Smallsize embryoid bodies have the advantage over the solid tumors that the location of their embryonal carcinoma cells is known: the latter comprise a "core" (Fig.…”

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confidence: 99%

Normal genetically mosaic mice produced from malignant teratocarcinoma cells.

Mintz¹,

Illmensee²

1975

Proc. Natl. Acad. Sci. U.S.A.

1,036

456

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3585The most rigorous test possible for developmental totipotency would be significant contributions of the carcinoma cells to the normal differentiation of virtually all tissues in a mouse. For this to occur, the initially malignant cells would presumably have to be brought into association with early embryo cells so that the latter could provide an organizational framework appropriate for normal development. The experiment is analogous to production of allophenic mice (6).The projected teratoma studies in this laboratory involve the use of mutagenized embryonal carcinoma cells for experimental analyses of genetic regulatory systems in mammalian differentiation (7). The most promising source of baseline, or nonmutagenized, cells appears to be from the cores of small embryoid bodies grown only in vivo, as these would be less likely to have accumulated genetic changes than would cells cultivated in vitro. Most in vitro teratocarcinoma cell lines do not in fact have a normal chromosome number and some have lost multipotentiality (8-11), whereas the tumors from which they originated were diploid (12).We report here that teratocarcinoma cells taken from the cores of embryoid bodies grown only in vivo for 8 years, during which they retained a euploid chromosome complement, appear to be developmentally totipotent. The original conversion to malignancy in all likelihood did not involve mutational events and has proved to be completely reversible to normalcy. A partial report of these results has been presented (7). MATERIALS AND METHODSCore Cells. The OTT 6050 ascites teratoma, originally received from Dr. L. C. Stevens, has been maintained by intraperitoneal transfers every 2-3 weeks in syngeneic males of the 129/Sv SlJ C P inbred strain (to be referred to as 129) (see Fig. 1). To obtain core cells, only small-size embryoid bodies were collected, in Dulbecco's phosphate-buffered saline (PBS), by filtration of ascites fluid through 100 /Am Nitex mesh (13). They were subjected to light proteolytic treatment for approximately 3 min in 0.25% trypsin (crystalline, Worthington) and 1.25% pancreatin (Difco) in PBS; proteolysis was stopped in Dulbecco's modification of Eagle's medium (DMEM) with 50% fetal calf serum (FCS) (Gibco). Addition of 5 ,gg/ml of DNase eliminated stickiness.After about 15 min, the embryoid bodies were centrifuged and transferred to DMEM with 15% FCS and organic buffers [10 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (Hepes) and 10 mM morpholinopropane sulfonic acid (Mops)], and the epithelium was peeled off with tungsten needles. The cores (Fig. 3) were then partially dissociat- [+/+].) The embryo was placed under a testis capsule, where it became disorganized, forming a teratoma which metastasized to a renal node. The primary tumor was minced and transplanted intraperitoneally; it became an ascites tumor of "embryoid bodies" with yolk sac "rinds" and teratocarcinoma (or embryonal carcinoma) "cores". In 1975, after almost 200 transplant generations in syngeneic hosts, the rinds of some...

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Zwischen Freiheit und Fremdbestimmung. Überlegungen zu H.G. Adlers ontologischer Panoramatik

Görner¹

2011

Monatshefte

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Rhythmus: Eine Begriffsbestimmung

Cited by 3 publications

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Totipotency and normal differentiation of single teratocarcinoma cells cloned by injection into blastocysts.

Totipotency and normal differentiation of single teratocarcinoma cells cloned by injection into blastocysts.

Normal genetically mosaic mice produced from malignant teratocarcinoma cells.

Zwischen Freiheit und Fremdbestimmung. Überlegungen zu H.G. Adlers ontologischer Panoramatik

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