In Vivo Osteoprogenitor Potency of Human Stromal Cells from Different Tissues Does Not Correlate with Expression of POU5F1 or Its Pseudogenes

Kaltz, Nikolas; Funari, Alessia; Hippauf, Sandra; Delorme, Bruno; Noël, Danièle; Riminucci, Mara; Jacobs, Volker R.; Häupl, Thomas; Jørgensen, Christian; Charbord, Pierre; Peschel, Christian; Bianco, Paolo; Oostendorp, Robert A.J.

doi:10.1634/stemcells.2008-0304

Cited by 44 publications

(26 citation statements)

References 31 publications

(65 reference statements)

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“…These observations are supported by previous studies describing the properties of MSC derived from different populations [57,58]. Therefore, it remains to be determined whether the differences in differentiation propensity result from the derivation of MSC from iPSC or whether they are dictated by the tissue of origin of the parental iPSC.…”

Section: Discussionsupporting

confidence: 64%

Generation of Functional Mesenchymal Stem Cells from Different Induced Pluripotent Stem Cell Lines

Hynes

Menicanin

Mrozik

et al. 2014

Stem Cells and Development

139

142

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The therapeutic potential of mesenchymal stem cells (MSC) has highlighted the need for identifying easily accessible and reliable sources of these cells. An alternative source for obtaining large populations of MSC is through the controlled differentiation of induced pluripotent stem cells (iPSC). In the present study, colonies of iPSC were cultured in MSC culture media for 2 weeks. Serial passaging then selected for fast growing MSClike cells with a typical fibroblastic morphology and the capacity to proliferate on standard culture flasks without feeder cells. MSC-like cells were developed from iPSC lines arising from three different somatic tissues: gingiva, periodontal ligament (PDL), and lung. The iPSC-MSC like cells expressed key MSC-associated markers (CD73, CD90, CD105, CD146, and CD166) and lacked expression of pluripotent markers (TRA160, TRA181, and alkaline phosphatase) and hematopoietic markers (CD14, CD34, and CD45). In vitro iPSC-MSC-like cells displayed the capacity to differentiate into osteoblasts, adipocytes, and chondrocytes. In vivo subcutaneous implantation of the iPSC-MSC-like cells into NOD/SCID mice demonstrated that only the PDL-derived iPSC-MSC-like cells exhibited the capacity to form mature mineralized structures which were histologically similar to mature bone. These findings demonstrate that controlled induction of iPSC into fibroblastic-like cells that phenotypically and functionally resemble adult MSC is an attractive approach to obtain a readily available source of progenitor cells for orthopedic and dental-related tissue-engineering applications. However, a detailed characterization of the iPSC-MSC-like cells will be important, as MSC-like cells derived from different iPSC lines exhibit variability in their differentiation capacity.

show abstract

Section: Discussionsupporting

confidence: 64%

Generation of Functional Mesenchymal Stem Cells from Different Induced Pluripotent Stem Cell Lines

Hynes

Menicanin

Mrozik

et al. 2014

Stem Cells and Development

139

142

View full text Add to dashboard Cite

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“…Our results indicated that the OCT4 gene was not expressed in human MSC or in fibroblasts, contradicting data from previous reports (Pochampally et al, 2004;Izadpanah et al, 2006;Greco et al, 2007;Go et al, 2008;Riekstina et al, 2009) but in agreement with other studies (Berg and Goodell, 2007;Lengner et al, 2007;Liedtke et al, 2007;Kaltz et al, 2008). This discrepancy found in the literature is due to the fact that OCT4 has at least 4 protein isoforms (OCT4A,) generated by an alternative splicing and alternative translation initiation (Wang and Dai, 2010).…”

Section: Discussionsupporting

confidence: 51%

Short Communication Forced expression of OCT4 influences the expression of pluripotent genes in human mesenchymal stem cells and fibroblasts

Palma¹,

Tannous²,

Malta³

et al. 2013

Genet. Mol. Res.

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ABSTRACT. Genetic reprogramming of adult cells to generate induced pluripotent stem (iPS) cells is a new and important step in sidestepping some of the ethical issues and risks involved in the use of embryonic stem cells. iPS cells can be generated by introduction of transcription factors, such as OCT4, SOX2, KLF4, and CMYC. iPS cells resemble embryonic stem cells in their properties and differentiation potential. The mechanisms that lead to induced pluripotency and the effect of each transcription factor are not completely understood. We performed a critical evaluation of the effect of overexpressing OCT4 in mesenchymal stem cells and fibroblasts and found that OCT4 can activate the expression of other stemness genes, such as SOX2, NANOG, CMYC, FOXD3, KLF4, and βCATENIN, which are not normally or are very weakly expressed in mesenchymal stem cells. Transient expression of OCT4 was also performed to evaluate Ectopic OCT4 expression activates other pluripotent genes whether these genes are affected by its overexpression in the first 48 h. Transfected fibroblast cells expressed around 275-fold more OCT4 than non-transfected cells. In transient expression, in which cells were analyzed after 48 h, we detected only the up-regulation of FOXD3, SOX2, and KLF4 genes, suggesting that these genes are the earlier targets of OCT4 in this cellular type. We conclude that forced expression of OCT4 can alter cell status and activate the pluripotent network. Knowledge gained through study of these systems may help us to understand the kinetics and mechanism of cell reprogramming.

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“…Many transcripts belonging to this set have already been reported by others as ''stemness'' genes downregulated after differentiation and upregulated after reversion to an undifferentiated state [16]. Not unexpectedly, this set does not include embryonic SC pluripotency genes and telomerase reverse transcriptase, already reported as nonexpressed by BM MSCs [42,43], but includes cytokines, such as interleukin 6, leukemia inhibitory factor and fibroblast growth factor 2, known to be essential for the maintenance of SCs in a proliferative state.…”

Section: Discussionmentioning

confidence: 76%

Specific Lineage-Priming of Bone Marrow Mesenchymal Stem Cells Provides the Molecular Framework for Their Plasticity

et al. 2009

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Lineage-priming is a molecular model of stem cell (SC) differentiation in which proliferating SCs express a subset of genes associated to the differentiation pathways to which they can commit. This concept has been developed for hematopoietic SCs, but has been poorly studied for other SC populations. Because the differentiation potential of human bone marrow mesenchymal stem cells (BM MSCs) remains controversial, we have explored the theory of lineage-priming applied to these cells. We show that proliferating primary layers and clones of BM MSCs have precise priming to the osteoblastic (O), chondrocytic (C), adipocytic (A), and the vascular smooth muscle (V) lineages, but not to skeletal muscle, cardiac muscle, hematopoietic, hepatocytic, or neural lineages. Priming was shown both at the mRNA (300 transcripts were evaluated) and the protein level. In particular, the master transactivator proteins PPARG, RUNX2, and SOX9 were coexpressed before differentiation induction in all cells from incipient clones. We further show that MSCs cultured in the presence of inducers differentiate into the lineages for which they are primed. Our data point out to a number of signaling pathways that might be activated in proliferating MSCs and would be responsible for the differentiation and proliferation potential of these cells. Our results extend the notion of lineage-priming and provide the molecular framework for inter-A, -O, -C, -V plasticity of BM MSCs. Our data highlight the use of BM MSCs for the cell therapy of skeletal or vascular disorders, but provide a word of caution about their use in other clinical indications.

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In Vivo Osteoprogenitor Potency of Human Stromal Cells from Different Tissues Does Not Correlate with Expression of POU5F1 or Its Pseudogenes

Cited by 44 publications

References 31 publications

Generation of Functional Mesenchymal Stem Cells from Different Induced Pluripotent Stem Cell Lines

Generation of Functional Mesenchymal Stem Cells from Different Induced Pluripotent Stem Cell Lines

Short Communication Forced expression of OCT4 influences the expression of pluripotent genes in human mesenchymal stem cells and fibroblasts

Specific Lineage-Priming of Bone Marrow Mesenchymal Stem Cells Provides the Molecular Framework for Their Plasticity

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