Experimental endocrine manipulation by contraceptive regimen in the male marmoset (Callithrix jacchus)

Wistuba, Joachim; Luetjens, C. Marc; Ehmcke, Jens; Redmαnn, K.; Damm, Oliver; Steinhoff, Annekatrin; Sandhowe-Klaverkamp, Reinhild; Nieschlag, Eberhard; Simoni, Manuela; Schlatt, Stefan

doi:10.1530/rep-12-0373

Cited by 17 publications

(8 citation statements)

References 42 publications

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“…We consider the generated iPS cell lines reprogrammed, although, as expected since under control of the CAG promoter [ 30 , 31 ], the introduced reprogramming cassette is not silenced. Since expression from the reprogramming cassette does not respond to the cells’ gene regulatory mechanisms, the expression from the endogenous loci has to be adjusted to the total amount of protein within the cells.…”

Section: Discussionmentioning

confidence: 99%

“…Based on the comparison of the expression of the reprogramming cassette and SOX2 expression levels in the one high-passage number iPS cell line (DPZcj_iPSC1) and the five lower-number iPS cell lines (DPZcj_iPSC2–6; see Fig. 2E ), we speculate that the expression of the reprogramming cassette, which is driven by the robust CAG promoter [ 30 , 31 ], is decreased slowly with increasing passage number. The expression level of the reprogramming cassette is lowest in DPZcj_iPSC1 (approximately at passage 80).…”

Section: Discussionmentioning

confidence: 99%

“…For this reason, we chose the common marmoset monkey ( Callithrix jacchus ) as a non-human primate species to generate iPS cells. The common marmoset is frequently used in biomedical research and recently gained increasing interest especially in the fields of stem cell research [ 29 , 30 ], reproductive biology [ 31 – 33 ] and neurobiology (reviewed in [ 34 , 35 ]). Its small size—yet representing primate physiology-, the absence of zoonoses, easy handling and relatively low housing costs are some of its important practical advantages further promoting the marmoset monkey as a bridging non-human primate species between rodent studies and clinical application.…”

Section: Introductionmentioning

confidence: 99%

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Non-Viral Generation of Marmoset Monkey iPS Cells by a Six-Factor-in-One-Vector Approach

et al. 2015

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Groundbreaking studies showed that differentiated somatic cells of mouse and human origin could be reverted to a stable pluripotent state by the ectopic expression of only four proteins. The resulting pluripotent cells, called induced pluripotent stem (iPS) cells, could be an alternative to embryonic stem cells, which are under continuous ethical debate. Hence, iPS cell-derived functional cells such as neurons may become the key for an effective treatment of currently incurable degenerative diseases. However, besides the requirement of efficacy testing of the therapy also its long-term safety needs to be carefully evaluated in settings mirroring the clinical situation in an optimal way. In this context, we chose the long-lived common marmoset monkey (Callithrix jacchus) as a non-human primate species to generate iPS cells. The marmoset monkey is frequently used in biomedical research and is gaining more and more preclinical relevance due to the increasing number of disease models. Here, we describe, to our knowledge, the first-time generation of marmoset monkey iPS cells from postnatal skin fibroblasts by non-viral means. We used the transposon-based, fully reversible piggyback system. We cloned the marmoset monkey reprogramming factors and established robust and reproducible reprogramming protocols with a six-factor-in-one-construct approach. We generated six individual iPS cell lines and characterized them in comparison with marmoset monkey embryonic stem cells. The generated iPS cells are morphologically indistinguishable from marmoset ES cells. The iPS cells are fully reprogrammed as demonstrated by differentiation assays, pluripotency marker expression and transcriptome analysis. They are stable for numerous passages (more than 80) and exhibit euploidy. In summary, we have established efficient non-viral reprogramming protocols for the derivation of stable marmoset monkey iPS cells, which can be used to develop and test cell replacement therapies in preclinical settings.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Non-Viral Generation of Marmoset Monkey iPS Cells by a Six-Factor-in-One-Vector Approach

et al. 2015

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“…Therefore, the common marmoset is the NHP model of choice for specific applications and purposes and nicely complements the macaque models. This is reflected by many studies performed in the fields of stem cell research 21 22 , reproductive biology 23 24 25 , developmental biology 26 27 , and neurobiology reviewed in refs 28 , 29 . Embryo-derived pluripotent stem cells of the common marmoset were first published in 1996 2 .…”

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confidence: 99%

The transcriptomes of novel marmoset monkey embryonic stem cell lines reflect distinct genomic features

Debowski

Drummer

Lentes

et al. 2016

Sci Rep

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Embryonic stem cells (ESCs) are useful for the study of embryonic development. However, since research on naturally conceived human embryos is limited, non-human primate (NHP) embryos and NHP ESCs represent an excellent alternative to the corresponding human entities. Though, ESC lines derived from naturally conceived NHP embryos are still very rare. Here, we report the generation and characterization of four novel ESC lines derived from natural preimplantation embryos of the common marmoset monkey (Callithrix jacchus). For the first time we document derivation of NHP ESCs derived from morula stages. We show that quantitative chromosome-wise transcriptome analyses precisely reflect trisomies present in both morula-derived ESC lines. We also demonstrate that the female ESC lines exhibit different states of X-inactivation which is impressively reflected by the abundance of the lncRNA X inactive-specific transcript (XIST). The novel marmoset ESC lines will promote basic primate embryo and ESC studies as well as preclinical testing of ESC-based regenerative approaches in NHP.

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“…Marmosets and tamarins seem to be the only anthropoid primate species that regularly exhibit multiple ovulations per cycle [25]. Because of these substantial differences, the clinical relevance of the marmoset for reproductive toxicity PART 8 SPECIAL TOXICITY TESTING WITH NHP assessment has been questioned, and unless there is no other choice, using this species for DART evaluation is not recommended [26]. If there is no other choice, however, there is precedence and limited historical data available for all three experimental designs of the standard DART study types in the marmoset.…”

Section: Which Nhp Model?mentioning

confidence: 99%

Developmental and Reproductive Toxicity Testing

Weinbauer

Bowman

Halpern³

et al. 2015

The Nonhuman Primate in Nonclinical Drug Development and Safety Assessment

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Experimental endocrine manipulation by contraceptive regimen in the male marmoset (Callithrix jacchus)

Cited by 17 publications

References 42 publications

Non-Viral Generation of Marmoset Monkey iPS Cells by a Six-Factor-in-One-Vector Approach

Non-Viral Generation of Marmoset Monkey iPS Cells by a Six-Factor-in-One-Vector Approach

The transcriptomes of novel marmoset monkey embryonic stem cell lines reflect distinct genomic features

Developmental and Reproductive Toxicity Testing

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