Activin A expression regulates multipotency of mesenchymal progenitor cells

Djouad, Farida; Jackson, Wesley M.; Bobick, Brent E.; Janjanin, Sasa; Song, Yingjie; Huang, George T.‐J.; Tuan, Rocky S.

doi:10.1186/scrt11

Cited by 51 publications

(55 citation statements)

References 59 publications

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“…According to the reports by our group and others, T-MSCs exhibit typical expression patterns of MSC surface markers (negative for CD14, CD34, and CD45; positive for CD73, CD90, and CD105) and have multilineage differentiation potential [14,15,16,17,40]. Previous studies also emphasized the relatively short doubling time of T-MSCs (about 38 h) compared with other types of MSCs (14–17).…”

Section: Discussionmentioning

confidence: 91%

See 1 more Smart Citation

Tonsil-Derived Mesenchymal Stem Cells Differentiate into a Schwann Cell Phenotype and Promote Peripheral Nerve Regeneration

Jung

Park

Choi

et al. 2016

IJMS

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Schwann cells (SCs), which produce neurotropic factors and adhesive molecules, have been reported previously to contribute to structural support and guidance during axonal regeneration; therefore, they are potentially a crucial target in the restoration of injured nervous tissues. Autologous SC transplantation has been performed and has shown promising clinical results for treating nerve injuries and donor site morbidity, and insufficient production of the cells have been considered as a major issue. Here, we performed differentiation of tonsil-derived mesenchymal stem cells (T-MSCs) into SC-like cells (T-MSC-SCs), to evaluate T-MSC-SCs as an alternative to SCs. Using SC markers such as CAD19, GFAP, MBP, NGFR, S100B, and KROX20 during quantitative real-time PCR we detected the upregulation of NGFR, S100B, and KROX20 and the downregulation of CAD19 and MBP at the fully differentiated stage. Furthermore, we found myelination of axons when differentiated SCs were cocultured with mouse dorsal root ganglion neurons. The application of T-MSC-SCs to a mouse model of sciatic nerve injury produced marked improvements in gait and promoted regeneration of damaged nerves. Thus, the transplantation of human T-MSCs might be suitable for assisting in peripheral nerve regeneration.

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Section: Discussionmentioning

confidence: 91%

“…In particular, the high proliferation rate of T-MSCs is very important for quantitative recovery and for the establishment of dependable cell lines. Several studies have confirmed that T-MSCs express typical MSC cell surface markers and can differentiate into mesodermal lineages [14,15,16]. …”

Section: Introductionmentioning

confidence: 99%

Tonsil-Derived Mesenchymal Stem Cells Differentiate into a Schwann Cell Phenotype and Promote Peripheral Nerve Regeneration

Jung

Park

Choi

et al. 2016

IJMS

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“…It contributes to internalization of Activin receptors, thus reducing the number of receptors available for ligand interaction, which in turn could inhibit signaling [47]. Activin A receptor was shown to be positively linked to chondrogenesis, with COL2 and sulfated GAGs being reduced when the Activin A receptor was knocked down [48]. Furthermore, RALA has been shown to inhibit exocytosis [49].…”

mentioning

confidence: 97%

microRNA-140 TargetsRALAand Regulates Chondrogenic Differentiation of Human Mesenchymal Stem Cells by Translational Enhancement ofSOX9andACAN

Karlsen

Jakobsen²,

Mikkelsen³

et al. 2014

Stem Cells and Development

113

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Lesions of articular cartilage do not heal spontaneously. One treatment strategy would be to make cartilage in the laboratory by directed chondrogenic differentiation of mesenchymal stem cells (MSCs). To promote our understanding of the molecular control of chondrogenesis, we have compared the changes in microRNAs (miRNAs) during in vitro chondrogenesis of MSCs with those observed in uncultured and dedifferentiated articular chondrocytes (ACs). Several miRNAs showed a reciprocal relationship during the differentiation of MSCs and dedifferentiation of ACs. miR-140-5p and miR-140-3p changed the most during in vitro chondrogenesis, they were the miRNAs most highly expressed in tissue-engineered chondrocytes, and they were also among the miRNAs most highly expressed in uncultured ACs. There was a 57% overlap for the 100 most highly expressed miRNAs in differentiated MSCs and uncultured ACs, but for other miRNAs, the expression pattern was quite different. We transiently and stably inhibited and overexpressed miR-140-5p and miR-140-3p in differentiating MSCs and dedifferentiating ACs, respectively, to describe global effects and identify and validate new targets. Surprisingly, SOX9 and aggrecan proteins were found to be downregulated in anti-miR-140 transduced differentiating MSCs despite unchanged mRNA levels. This suggests that miR-140 stimulates in vitro chondrogenesis by the upregulation of these molecules at the protein level. RALA, a small GTPase, was identified as a miR-140 target and knockdown experiments showed that RALA regulated SOX9 at the protein level. These observations shed new light on the effect of miR-140 for chondrogenesis in vitro and in vivo.

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“…1). Activin A has been defined to trigger PS/ME lineages in both ESCs and iPSCs [41, 56–58]; however, it maintains multipotency in MSCs [59]. The differences in the role of Activin A are related to the differences in stem cell origins and their developmental stages.…”

Section: Discussionmentioning

confidence: 99%

Defined three-dimensional culture conditions mediate efficient induction of definitive endoderm lineage from human umbilical cord Wharton’s jelly mesenchymal stem cells

et al. 2016

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BackgroundWharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) are gaining increasing interest as an alternative source of stem cells for regenerative medicine applications. Definitive endoderm (DE) specification is a prerequisite for the development of vital organs such as liver and pancreas. Hence, efficient induction of the DE lineage from stem cells is crucial for subsequent generation of clinically relevant cell types. Here we present a defined 3D differentiation protocol of WJ-MSCs into DE cells.MethodsWJ-MSCs were cultured in suspension to generate spheroids, about 1500 cells each, for 7 days. The serum-free differentiation media contained specific growth factors, cytokines, and small molecules that specifically regulate signaling pathways including sonic hedgehog, bone morphogenetic protein, Activin/Wnt, and Notch.ResultsWe obtained more than 85 % DE cells as shown with FACS analysis using antibodies directed against the DE marker CXCR4. In addition, biochemical and molecular analysis of bona-fide DE markers revealed a time-course induction of Sox17, CXCR4, and FoxA2. Focused PCR-based array also indicated a specific induction into the DE lineage.ConclusionsIn this study, we report an efficient serum-free protocol to differentiate WJ-MSCs into DE cells utilizing 3D spheroid formation. Our approach might aid in the development of new protocols to obtain DE-derivative lineages including liver-like and pancreatic insulin-producing cells.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-016-0426-9) contains supplementary material, which is available to authorized users.

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Activin A expression regulates multipotency of mesenchymal progenitor cells

Cited by 51 publications

References 59 publications

Tonsil-Derived Mesenchymal Stem Cells Differentiate into a Schwann Cell Phenotype and Promote Peripheral Nerve Regeneration

Tonsil-Derived Mesenchymal Stem Cells Differentiate into a Schwann Cell Phenotype and Promote Peripheral Nerve Regeneration

microRNA-140 TargetsRALAand Regulates Chondrogenic Differentiation of Human Mesenchymal Stem Cells by Translational Enhancement ofSOX9andACAN

Defined three-dimensional culture conditions mediate efficient induction of definitive endoderm lineage from human umbilical cord Wharton’s jelly mesenchymal stem cells

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