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Gödöllő, Hungary

Hall V.J.,Copenhagen University | Kristensen M.,Copenhagen University | Rasmussen M.A.,Copenhagen University | Ujhelly O.,BioTalentum Ltd | And 4 more authors.
Cellular Reprogramming

Porcine induced pluripotent stem cells (piPSCs) have the capacity to differentiate in vitro and in vivo and form chimeras. However, the lack of transgene silencing of exogenous DNA integrated into the genome and the inability of cells to proliferate in the absence of transgene expression are underlying reported problems, suggesting that reprogramming is not complete. The aim of the present study was to evaluate reprogramming events using a partially reprogrammed piPSC-like line expressing hOCT4, hNANOG, and hcMYC under tetracycline-regulated control to investigate the effects of these particular transgenes on the expression of the porcine endogenous pluripotency machinery. Endogenous and exogenous gene expression of OCT4, NANOG, SOX2, KLF4, and cMYC was determined at passages 5, 10, 15, and 20, both in cells cultured at 1 μg/mL doxycycline or 4 μg/mL doxycycline. Our results revealed that endogenous genes are repressed by their transgene counterparts in culture and that lack of expression of the transgenes, SOX2 and KLF4 allows for expression of endogenous SOX2 and KLF4. Furthermore, we report that alternate endogenous transcripts for pNANOG, pSOX2, and pKLF4 can also be detected in the pig. Despite the ability for some endogenous genes to be expressed in these lines, the piPSC-like cells still cannot be maintained without doxycycline, indicating that the culture system of piPSCs may not be optimal or that the reprogramming factor combination used may not currently be optimal for maintaining pluripotency in the pig. This may help to explain the difficulties in producing stable piPSCs and bona fide embryonic stem cell lines in this species. © Mary Ann Liebert, Inc. Source

Raveh-Amit H.,BioTalentum Ltd | Berzsenyi S.,BioTalentum Ltd | Vas V.,Szent Istvan University | Ye D.,BioTalentum Ltd | And 3 more authors.

Aging is accompanied by reduced regenerative capacity of all tissues and organs and dysfunction of adult stem cells. Notably, these age-related alterations contribute to distinct pathophysiological characteristics depending on the tissue of origin and function and thus require special attention in a type by type manner. In this paper, we review the current understanding of the mechanisms leading to tissue-specific adult stem cell dysfunction and reduced regenerative capacity with age. A comprehensive investigation of the hematopoietic, the neural, the mesenchymal, and the skeletal stem cells in age-related research highlights that distinct mechanisms are associated with the different types of tissue stem cells. The link between age-related stem cell dysfunction and human pathologies is discussed along with the challenges and the future perspectives in stem cell-based therapies in age-related diseases. © 2013 The Author(s). Source

Deshmukh R.S.,BioTalentum Ltd | Kovacs K.A.,BioTalentum Ltd | Dinnyes A.,BioTalentum Ltd | Dinnyes A.,Szent Istvan University | Dinnyes A.,University Utrecht
Stem Cells International

Development of induced pluripotent stem cells (iPSCs) using forced expression of specific sets of transcription factors has changed the field of stem cell research extensively. Two important limitations for research application of embryonic stem cells (ESCs), namely, ethical and immunological issues, can be circumvented using iPSCs. Since the development of first iPSCs, tremendous effort has been directed to the development of methods to increase the efficiency of the process and to reduce the extent of genomic modifications associated with the reprogramming procedure. The established lineage-specific differentiation protocols developed for ESCs are being applied to iPSCs, as they have great potential in regenerative medicine for cell therapy, disease modeling either for drug development or for fundamental science, and, last but not least, toxicity testing. This paper reviews efforts aimed at practical development of iPSC differentiation to neural/cardiac lineages and further the use of these iPSCs-derived cells for drug development and toxicity testing. © Copyright 2012 Rahul S. Deshmukh et al. Source

Cebrian-Serrano A.,BioTalentum Ltd | Stout T.,University Utrecht | Dinnyes A.,BioTalentum Ltd | Dinnyes A.,University Utrecht | Dinnyes A.,Szent Istvan University
Veterinary Journal

Induced pluripotent stem cells (iPSCs) can now be derived from a tissue biopsy and represent a promising new platform for disease modelling, drug and toxicity testing, biomarker development and cell-based therapies for regenerative medicine. In regenerative medicine, large animals may represent the best models for man, and thereby provide invaluable systems in which to test the safety and the potential of iPSCs. Hence, testing iPSCs in veterinary species may serve a double function, namely, developing therapeutic products for regenerative medicine in veterinary patients while providing valuable background information for human clinical trials. The production of iPSCs from livestock or wild species is attractive because it could improve efficiency and reduce costs in various fields, such as transgenic animal generation and drug development, preservation of biological diversity, and because it also offers an alternative to xenotransplantation for in vivo generation of organs. Although the technology of cellular reprogramming using the so-called 'Yamanaka factors' is in its peak expectation phase and many concerns still need to be addressed, the rapid technical progress suggests that iPSCs could contribute significantly to novel therapies in veterinary and biomedical practice in the near future. This review provides an overview of the potential applications of iPSCs in veterinary medicine. © 2013 Elsevier Ltd. Source

Pirity M.K.,BioTalentum Ltd | Dinnyes A.,BioTalentum Ltd | Dinnyes A.,Szent Istvan University
Stem Cell Research and Therapy

Induced pluripotent stem cells (iPSCs) are novel tools for biomedical research, with a promise for future regenerative medicine applications. Recently, Han and colleagues reported in Nature that T box gene 3 (Tbx3) can improve the quality of mouse iPSCs and increase their germline transmission efficacy. This observation contributes greatly to the improvement of iPSC technology and might be a step towards 'designer' reprogramming strategies by generating high quality iPSCs. Further studies comparing pluripotency regulation in different species, including that in human, will be necessary to verify the universal role of Tbx3 and the medical relevance of the observation. © 2010 BioMed Central Ltd. Source

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