Adipose tissue-derived mesenchymal stromal cells efficiently differentiate into insulin-producing cells in pancreatic islet microenvironment both in vitro and in vivo

Karaöz, Erdal; Okçu, Alparslan; Ünal, Zehra Seda; Subaşı, Cansu; Sağlam, Özlem; Duruksu, Gökhan

doi:10.1016/j.jcyt.2013.01.005

Cited by 84 publications

(86 citation statements)

References 41 publications

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“…We found that the clusters appeared after 15 days of differentiation, a much longer period when compared to the differentiation of insulin-producing cells from embryonic stem cells (Boyd et al, 2008). However, similar to our study, it took more than 10 days to induce the formation of clusters in the differentiation of insulin-producing cells from adipose tissue derived stromal cells by co-culture with isolated islets (Karaoz et al, 2013). identified that mesenchymal stem cells trans-differentiated into insulin-producing cells via the expression of nestin, a neural stem cell marker.…”

Section: Discussionsupporting

confidence: 84%

Production of islet-like insulin-producing cell clusters in vitro from adiposederived stem cells

Dang¹,

Bui²,

Pham³

et al. 2015

Biomed Res Ther

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Abstract-Diabetes mellitus is a high incidence disease that has increased rapidly in recent years. Many new therapies are being studied and developed in order to find an effective treatment. An ideal candidate is stem cell therapy. In this study, we investigated the differentiation of adipose derived stem cells (ADSCs) into pseudo-islets in defined medium in vitro, to produce large quantities of insulin-producing cells (IPCs) for transplantation. ADSCs isolated from adipose tissue were induced to differentiate into islet-like insulin-producing cell clusters in vitro by inducing medium DMEM/F12 containing nicotinamide, N2, B27, bFGF, and insulin-transferrin-selenite (ITS). Differentiated cells were analyzed for properties of IPCs, including storage of Zn 2+ by dithizone staining, insulin production by ELISA and immunochemistry, and beta cell-related gene expression by reverse transcriptase PCR. The results showed that after 2 weeks of differentiation, the ADSCs aggregated into cell clusters, and after 4 weeks they formed islets, 50-400 micrometers in diameter. These islet cells exhibited characteristics of pancreatic beta cells as they were positive for dithizone staining, expressed insulin in vitro and C-peptide in the cytoplasm, and expressed pancreatic beta cellspecific genes, including Pdx-1, NeuroD, and Ngn3. These results demonstrate that ADSCs can be used to produce a large number of functional islets for research as well as application.

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Section: Discussionsupporting

confidence: 84%

Production of islet-like insulin-producing cell clusters in vitro from adiposederived stem cells

Dang¹,

Bui²,

Pham³

et al. 2015

Biomed Res Ther

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“…Gonzalez et al [13] showed that MSCs can express pluripotency-related genes, and even more interesting these MSCs were isolated from adult human testes, which could indicate that these cells and PO-MSCs originate from the same cells in the developmental stage of indifferent gonads. Moreover, there are more and more studies confirming the trans-differentiation potential of MSCs [49][50][51][52][53][54][55] which makes them still more interesting to be applied in regenerative medicine and cellular therapies in the future. In the case of cells cultured in this study, we would particularly suggest using them in the frame of restoring ovarian function in cases of its impairment or of premature ovarian failure.…”

Section: Discussionmentioning

confidence: 99%

Putative mesenchymal stem cells isolated from adult human ovaries

Štimpfel

Cerkovnik

Novaković

et al. 2014

J Assist Reprod Genet

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Purpose The purpose of this study was to show that healthy adult human ovaries can be a source of cells showing typical MSCs characteristics under in vitro conditions. Methods and results The cells, which were isolated from ovarian cortex tissue and named putative ovarian mesenchymal stem cells (PO-MSCs), were compared to bone marrowderived MSCs (BM-MSCs) and to adult human dermal fibroblasts (HDFs). The results of a gene expression analysis using the Human Mesenchymal Stem Cell RT² Profiler™ PCR Array revealed that PO-MSCs were different than fibroblasts. They expressed most of the analyzed genes as BM-MSCs, although some genes were differentially expressed. However, the heterogeneity of PO-MSCs samples was revealed. The PO-MSCs expressed the characteristic genes related to MSCs, such as CD105, CD44, CD90, M-CAM, CD73 and VCAM1. In addition, the expression of markers CD44, CD90, M-CAM and STRO-1 was confirmed in PO-MSCs using immunocytochemistry. The PO-MSCs showed multipotent character, since they were able to differentiate into the cells of adipogenic, osteogenic, neural and pancreatic lineage. Conclusions Healthy adult human ovaries can harbour an interesting population of cells showing typical MSCs characteristics under in vitro conditions and for this reason we named these cells putative MSCs. These cells express genes encoding main MSCs markers and have an interesting differential potential. Based on these results, we propose PO-MSCs as a novel type of MSCs which share some similarities with BMMSCs. Nevertheless they show distinct and specific characteristics and are not fibroblasts.

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“…These expanded ADSCs exhibit the MSC phenotype (Bourin et al, 2013;Zimmerlin et al, 2013), as is evidenced by the expression of MSC markers such as CD44, CD73, CD90 and CD105. These cells also successfully differentiate into adipocytes, osteoblasts, and chondrocytes, and could be trans-differentiated into other mesoderm cell types such as insulin producing cells (Karaoz et al, 2013;Moshtagh et al, 2013), hepatocytes (Aurich et al, 2009;Lee et al, 2012;Okura et al, 2010), and neuronal-like cells (Cardozo et al, 2010;Rezanejad et al, 2014). (Sandor et al, 2014), non-revascularizable critical limb ischemia (Bura et al, 2014), acute myocardial infarction and heart failure (Panfilov et al, 2013), complex perianal fistula in Crohn's disease (de la Portilla et al, 2013;Garcia-Olmo et al, 2009), and chronic myocardial ischemia (Qayyum et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Good manufacturing practice-compliant isolation and culture of human adipose derived stem cells

Pham¹,

Vu²,

Le³

et al. 2014

Biomed Res Ther

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Abstract-Adipose-derived stem cells (ADSCs) are excellent for regenerative medicine. Like mesenchymal stem cells, ADSCs possess multi-potent differentiation capacity that enables them to differentiate into osteoblasts, chondrocytes and adipocytes, as well as trans-differentiation into other cells. ADSC transplantation has gained attention in recent years, especially in vitro expanded ADSC transplantation. This study aimed to provide a new method to in vitro primarily culture and secondary culture of ADSCs that were compliant with good manufacturing practice for clinical applications. Stromal vascular fraction (SVF) was extracted from adipose tissue by commercial kits. SVF was expanded in vitro in medium with non-allogeneic supplements. Cultured ADSCs maintained immune-phenotype, karyotype, and differentiation potential after ten passages. Moreover, ADSCs at 15th passage could not form tumors in NOD/SCID mice. This research produced a suitable protocol for clinical applications of expanded ADSCs.

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Adipose tissue-derived mesenchymal stromal cells efficiently differentiate into insulin-producing cells in pancreatic islet microenvironment both in vitro and in vivo

Cited by 84 publications

References 41 publications

Production of islet-like insulin-producing cell clusters in vitro from adiposederived stem cells

Production of islet-like insulin-producing cell clusters in vitro from adiposederived stem cells

Putative mesenchymal stem cells isolated from adult human ovaries

Good manufacturing practice-compliant isolation and culture of human adipose derived stem cells

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