PDGF, TGF-β, and FGF signaling is important for differentiation and growth of mesenchymal stem cells (MSCs): transcriptional profiling can identify markers and signaling pathways important in differentiation of MSCs into adipogenic, chondrogenic, and osteogenic lineages

Blood ◽  
2008 ◽  
Vol 112 (2) ◽  
pp. 295-307 ◽  
Author(s):  
Felicia Ng ◽  
Shayne Boucher ◽  
Susie Koh ◽  
Konduru S. R. Sastry ◽  
Lucas Chase ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Signaling Pathways ◽  
Transforming Growth Factor ◽  
Transcriptional Profiling ◽  
Global Gene Expression ◽  
Cell Surface Receptor ◽  
Fgf Signaling ◽  
Global Gene Expression Profiling

Abstract We compared the transcriptomes of marrow-derived mesenchymal stem cells (MSCs) with differentiated adipocytes, osteocytes, and chondrocytes derived from these MSCs. Using global gene-expression profiling arrays to detect RNA transcripts, we have identified markers that are specific for MSCs and their differentiated progeny. Further, we have also identified pathways that MSCs use to differentiate into adipogenic, chondrogenic, and osteogenic lineages. We identified activin-mediated transforming growth factor (TGF)–β signaling, platelet-derived growth factor (PDGF) signaling and fibroblast growth factor (FGF) signaling as the key pathways involved in MSC differentiation. The differentiation of MSCs into these lineages is affected when these pathways are perturbed by inhibitors of cell surface receptor function. Since growth and differentiation are tightly linked processes, we also examined the importance of these 3 pathways in MSC growth. These 3 pathways were necessary and sufficient for MSC growth. Inhibiting any of these pathways slowed MSC growth, whereas a combination of TGF-β, PDGF, and β-FGF was sufficient to grow MSCs in a serum-free medium up to 5 passages. Thus, this study illustrates it is possible to predict signaling pathways active in cellular differentiation and growth using microarray data and experimentally verify these predictions.

scholarly journals Akt signaling is activated by TGFβ2 and impacts tenogenic induction of mesenchymal stem cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sophia K. Theodossiou ◽  
Jett B. Murray ◽  
LeeAnn A. Hold ◽  
Jeff M. Courtright ◽  
Anne M. Carper ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Signaling Pathways ◽  
Transforming Growth Factor ◽  
Akt Signaling ◽  
Cell Alignment ◽  
Limited Information ◽  
Akt Inhibitor ◽  
Tenogenic Differentiation

Abstract Background Tissue engineered and regenerative approaches for treating tendon injuries are challenged by the limited information on the cellular signaling pathways driving tenogenic differentiation of stem cells. Members of the transforming growth factor (TGF) β family, particularly TGFβ2, play a role in tenogenesis, which may proceed via Smad-mediated signaling. However, recent evidence suggests some aspects of tenogenesis may be independent of Smad signaling, and other pathways potentially involved in tenogenesis are understudied. Here, we examined the role of Akt/mTORC1/P70S6K signaling in early TGFβ2-induced tenogenesis of mesenchymal stem cells (MSCs) and evaluated TGFβ2-induced tenogenic differentiation when Smad3 is inhibited. Methods Mouse MSCs were treated with TGFβ2 to induce tenogenesis, and Akt or Smad3 signaling was chemically inhibited using the Akt inhibitor, MK-2206, or the Smad3 inhibitor, SIS3. Effects of TGFβ2 alone and in combination with these inhibitors on the activation of Akt signaling and its downstream targets mTOR and P70S6K were quantified using western blot analysis, and cell morphology was assessed using confocal microscopy. Levels of the tendon marker protein, tenomodulin, were also assessed. Results TGFβ2 alone activated Akt signaling during early tenogenic induction. Chemically inhibiting Akt prevented increases in tenomodulin and attenuated tenogenic morphology of the MSCs in response to TGFβ2. Chemically inhibiting Smad3 did not prevent tenogenesis, but appeared to accelerate it. MSCs treated with both TGFβ2 and SIS3 produced significantly higher levels of tenomodulin at 7 days and morphology appeared tenogenic, with localized cell alignment and elongation. Finally, inhibiting Smad3 did not appear to impact Akt signaling, suggesting that Akt may allow TGFβ2-induced tenogenesis to proceed during disruption of Smad3 signaling. Conclusions These findings show that Akt signaling plays a role in TGFβ2-induced tenogenesis and that tenogenesis of MSCs can be initiated by TGFβ2 during disruption of Smad3 signaling. These findings provide new insights into the signaling pathways that regulate tenogenic induction in stem cells.

scholarly journals Synthesis of embryonic tendon-like tissue by human marrow stromal/mesenchymal stem cells requires a three-dimensional environment and transforming growth factor β3

2010 ◽  
Vol 29 (8) ◽  
pp. 668-677 ◽  
Author(s):  
Zoher Kapacee ◽  
Ching-Yan Chloé Yeung ◽  
Yinhui Lu ◽  
David Crabtree ◽  
David F. Holmes ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Three Dimensional ◽  
Embryonic Tendon

scholarly journals Mesenchymal Stem Cells and Transforming Growth Factor-β3 (TGF-β3) to Enhance the Regenerative Ability of an Albumin Scaffold in Full Thickness Wound Healing

2018 ◽  
Vol 9 (4) ◽  
pp. 65 ◽  
Author(s):  
Dale Feldman ◽  
John McCauley
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Surgical Treatment ◽  
Growth Factor ◽  
Healing Rate ◽  
Pressure Ulcers ◽  
Transforming Growth Factor ◽  
Bed Rest ◽  
Full Thickness ◽  
Non Surgical Treatment

Pressure ulcers are one of the most common forms of skin injury, particularly in the spinal cord injured (SCI). Pressure ulcers are difficult to heal in this population requiring at least six months of bed rest. Surgical treatment (grafting) is the fastest recovery time, but it still requires six weeks of bed rest plus significant additional costs and a high recurrence rate. A significant clinical benefit would be obtained by speeding the healing rate of a non-surgical treatment to close to that of surgical treatment (approximately doubling of healing rate). Current non-surgical treatment is mostly inactive wound coverings. The goal of this project was to look at the feasibility of doubling the healing rate of a full-thickness defect using combinations of three treatments, for the first time, each shown to increase healing rate: application of transforming growth factor-β3 (TGF-β3), an albumin based scaffold, and mesenchymal stem cells (MSCs). At one week following surgery, the combined treatment showed the greatest increase in healing rate, particularly for the epithelialization rate. Although the target level of a 100% increase in healing rate over the control was not quite achieved, it is anticipated that the goal would be met with further optimization of the treatment.

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