Abstract
Clinical application of regenerative therapies using embryonic or induced pluripotent stem cells is within reach. Progress made during recent years has encouraged researchers to address remaining open questions in order to finally translate experimental cell replacement therapies into application in patients. To achieve this, studies in translationally relevant animal models are required to make the final step to the clinic. In this context, the baboon (Papio anubis) may represent a valuable nonhuman primate (NHP) model to test cell replacement therapies because of its close evolutionary relationship to humans and its large body size. In this study, we describe the reprogramming of adult baboon skin fibroblasts using the piggyBac transposon system. Via transposon-mediated overexpression of six reprogramming factors, we generated five baboon induced pluripotent stem cell (iPSC) lines. The iPSC lines were characterized with respect to alkaline phosphatase activity, pluripotency factor expression analysis, teratoma formation potential, and karyotype. Furthermore, after initial cocultivation with mouse embryonic fibroblasts, we were able to adapt iPSC lines to feeder-free conditions. In conclusion, we established a robust and efficient protocol for iPSC generation from adult baboon fibroblasts.
Highlights
The development of successful approaches for the induction of pluripotency in somatic cells to generate induced pluripotent stem cells was ground-breaking (Takahashi and Yamanaka, 2006)
Using a six-factor-in-one vector transposon, we reported the successful reprogramming of marmoset monkey (Callithrix jacchus) postnatal skin fibroblasts into induced pluripotent stem cell (iPSC) (Debowski et al, 2015)
Five independent baboon iPSC (biPSC) lines, termed DPZ_biPSC1 to DPZ_biPSC5, were derived from fibroblasts isolated from a skin biopsy of an adult female baboon
Summary
The development of successful approaches for the induction of pluripotency in somatic cells to generate induced pluripotent stem cells (iPSCs) was ground-breaking (Takahashi and Yamanaka, 2006). IPSCs overcame the practical and ethical difficulties associated with the use of embryonic stem cells (ESCs) for cell replacement therapies (CRTs) (Takahashi et al, 2007). The combined efforts of researchers resulted in a broad panel of reprogramming methods for the generation of iPSCs (Malik and Mahendra, 2013; Patel and Yang, 2010). This allows the exploration of different strategies for cell reprogramming, impacting potential CRTs in humans (Sosa et al, 2017; Zhang et al, 2017). Several aspects need to be addressed before routine clinical application including (i) long-term safety, (ii) survival and prevalence of Published by Copernicus Publications on behalf of the Deutsches Primatenzentrum GmbH (DPZ)
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