scholarly journals Neuropilin 1 Mediates Keratinocyte Growth Factor Signaling in Adipose-Derived Stem Cells: Potential Involvement in Adipogenesis

2018 ◽  
Vol 2018 ◽  
pp. 1-18 ◽  
Author(s):  
Simona Ceccarelli ◽  
Cristina Nodale ◽  
Enrica Vescarelli ◽  
Paola Pontecorvi ◽  
Valeria Manganelli ◽  
...  

Adipogenesis is regulated by a complex network of molecules, including fibroblast growth factors. Keratinocyte growth factor (KGF) has been previously reported to promote proliferation on rat preadipocytes, although the expression of its specific receptor, FGFR2-IIIb/KGFR, is not actually detected in mesenchymal cells. Here, we demonstrate that human adipose-derived stem cells (ASCs) show increased expression of KGF during adipogenic differentiation, especially in the early steps. Moreover, KGF is able to induce transient activation of ERK and p38 MAPK pathways in these cells. Furthermore, KGF promotes ASC differentiation and supports the activation of differentiation pathways, such as those of PI3K/Akt and the retinoblastoma protein (Rb). Notably, we observed only a low amount of FGFR2-IIIb in ASCs, which seems not to be responsible for KGF activity. Here, we demonstrate for the first time that Neuropilin 1 (NRP1), a transmembrane glycoprotein expressed in ASCs acting as a coreceptor for some growth factors, is responsible for KGF-dependent pathway activation in these cells. Our study contributes to clarify the molecular bases of human adipogenesis, demonstrating a role of KGF in the early steps of this process, and points out a role of NRP1 as a previously unknown mediator of KGF action in ASCs.

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Alice E. Mortimer ◽  
Alessandro Faroni ◽  
Mahmut A. Kilic ◽  
Adam J. Reid

Differentiating human adipose-derived stem cells (ASCs) towards Schwann cells produces an unstable phenotype when stimulating factors are withdrawn. Here, we set out to examine the role of glial growth factor 2 (GGF-2) in the maintenance of Schwann-like cells. Following ASC differentiation to Schwann-like cells, stimulating factors were withdrawn such that cells either remained in media supplemented with all stimulating factors, GGF-2 alone, or underwent complete withdrawal of all factors. Furthermore, each stimulating factor was also removed from the growth medium individually. At 72 hours, gene (qRT-PCR) and protein (ELISA) expression of key Schwann cell factors were quantified and cell morphology was analysed. Cells treated with GGF-2 alone reverted to a stem cell morphology and did not stimulate the production of brain-derived neurotrophic factor (BDNF), regardless of the concentration of GGF-2 in the growth medium. However, GGF-2 alone increased the expression of Krox20, the main transcription factor involved in myelination, relative to those cells treated with all stimulating factors. Cells lacking fibroblast growth factor were unable to maintain a Schwann-like morphology, and those lacking forskolin exhibited a downregulation in BDNF production. Therefore, it is likely that the synergistic action of multiple growth factors is required to maintain Schwann-like phenotype in differentiated ASCs.


1987 ◽  
Vol 80 (9) ◽  
pp. 591-593
Author(s):  
A J Barrett

At this meeting of the RSM's Section of Pathology, the regulation of haemopoietic stem cells and growth factors regulating various cell lines were described, and the role of oncogenes, platelet-derived growth factor and nerve growth factor in growth regulation was discussed.


1994 ◽  
Vol 345 (1313) ◽  
pp. 257-263 ◽  

Our previous studies have shown that haemopoietic stem cells undergo apoptotic death as a consequence of growth factor withdrawal. In this paper we review the new data that has accumulated since this observation and compare it with older data from the ‘pre-apoptotic’ age. Models of erythropoiesis and granulopoiesis that incorporate apoptosis as a normal physiological process controlling homeostasis are examined. The converse to cell death is cell survival, and we describe experiments which suggest that haemopoietic growth factors can not only act as mitogenic or differentiation stimuli but also act as survival signals. We, and others, have proposed that these growth factor-induced survival signals act through the membrane bound polypeptide receptors and share common features of signal transduction with proliferative responses. Enforced expression of bcl-2 in haemopoietic stem cells is able to overcome apoptosis following the withdrawal of growth factor, and the cells commit into different lineage differentiation programmes. Such cells spontaneously differentiate without cell division, suggesting a stochastic model of haemopoiesis in which the major role of haemopoietic growth factors is to suppress apoptosis and act as mitogens. We review the evidence that the underlying causes of some haematological diseases may be associated with change in the balance between cell survival and death.


2020 ◽  
Vol 21 (17) ◽  
pp. 6181
Author(s):  
Sara Cruciani ◽  
Giuseppe Garroni ◽  
Francesca Balzano ◽  
Renzo Pala ◽  
Emanuela Bellu ◽  
...  

Fat tissue represents an important source of adipose-derived stem cells (ADSCs), which can differentiate towards several phenotypes under certain stimuli. Definite molecules as vitamin D are able to influence stem cell fate, acting on the expression of specific genes. In addition, miRNAs are important modulating factors in obesity and numerous diseases. We previously identified specific conditioned media able to commit stem cells towards defined cellular phenotypes. In the present paper, we aimed at evaluating the role of metformin on ADSCs differentiation. In particular, ADSCs were cultured in a specific adipogenic conditioned medium (MD), in the presence of metformin, alone or in combination with vitamin D. Our results showed that the combination of the two compounds is able to counteract the appearance of an adipogenic phenotype, indicating a feedforward regulation on vitamin D metabolism by metformin, acting on CYP27B1 and CYP3A4. We then evaluated the role of specific epigenetic modulating genes and miRNAs in controlling stem cell adipogenesis. The combination of the two molecules was able to influence stem cell fate, by modulating the adipogenic phenotype, suggesting their possible application in clinical practice in counteracting uncontrolled lipogenesis and obesity-related diseases.


Author(s):  
Monia Savi ◽  
Leonardo Bocchi ◽  
Emanuela Fiumana ◽  
Caterina Frati ◽  
Francesca Bonafé ◽  
...  

We tested the hypothesis that cardiac regeneration through local delivery of adipose-derived stem cells (ASCs), activation of resident cardiac stem cells via growth factors (GFs) [hepatocyte growth factor (HGF) and insulin-like growth factor 1 (IGF-1):GFs] or both, are improved by pharmacologically active microcarriers (PAMs) interacting with cells/molecules conveyed on their surface. Rats with one-month old myocardial infarction were treated with ASCs, ASCs+PAMs, GF-releasing PAMs, ASCs+GF-releasing PAMs or vehicle. Two weeks later, hemodynamic function and inducibility of ventricular arrhythmias (VAs) were assessed. Eventually, the hearts were subjected to anatomical and immunohistochemical analyses. A significant ASCs engraftment and the largest improvement in cardiac mechanics occurred in ASC+GF-releasing PAM rats which by contrast were more vulnerable to VAs. Thus, PAMs may improve cell/GF-based cardiac regeneration although caution should be paid on the electrophysiological impact of their physical interaction with the myocardium.


PLoS ONE ◽  
2013 ◽  
Vol 8 (5) ◽  
pp. e63638 ◽  
Author(s):  
Mette Hemmingsen ◽  
Søren Vedel ◽  
Peder Skafte-Pedersen ◽  
David Sabourin ◽  
Philippe Collas ◽  
...  

Author(s):  
Feng Qin ◽  
Wenchao Zhang ◽  
Mingzi Zhang ◽  
Xiao Long ◽  
Loubin Si ◽  
...  

AbstractBackgroundAdipose-derived stem cells (ASCs) are considered promising cells for skin rejuvenation. However, whether the angiogenetic effect of ASCs plays an important role in the treatment of aging skin and its influence on skin tissue remain elusive.ObjectivesThe aim of this study was to evaluate the effect of ASCs on angiogenesis and local tissue water (LTW) in the aging skin of nude mice.MethodsTwelve nude mice were randomly divided into a UVB-induced photoaging group and a natural aging group. After the mouse model had been established, ASCs and phosphate-buffered saline (PBS) were then each injected into different sides of the dorsal skin of the mice. Blood perfusion and LTW content were measured. After 7 weeks, mice were killed, and skin samples were collected to measure the thickness of the dermis, the density of the capillaries, and the expression of angiogenic growth factors.ResultsASC therapy significantly increased the thickness of the dermis, the number of capillaries, and the expression of some angiogenic growth factors (vascular endothelial growth factor, insulin-like growth factor 1, and epidermal growth factor). At 7 weeks after injection, blood perfusion was significantly higher on the side injected with ASCs than on the side injected with PBS. LTW content was increased in the PBS-injected side, but the ASC-injected side showed no significant changes over time.ConclusionsASCs increased dermal thickness, promoted angiogenesis, and reduced LTW content in the skin of photoaging mice, providing a potential clinical therapy for skin rejuvenation.


Nanoscale ◽  
2018 ◽  
Vol 10 (19) ◽  
pp. 8947-8952 ◽  
Author(s):  
Saman Modaresi ◽  
Settimio Pacelli ◽  
Jonathan Whitlow ◽  
Arghya Paul

This study investigates the role of substrate stiffness in the non-viral transfection of human adipose-derived stem cells (hASCs) with the aim to maximize the hASC expression of vascular endothelial growth factor (VEGF).


Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3123
Author(s):  
Brandan Walters ◽  
Paul A. Turner ◽  
Bernd Rolauffs ◽  
Melanie L. Hart ◽  
Jan P. Stegemann

Adipose-derived stem cells (ASCs) are an abundant and easily accessible multipotent stem cell source with potential application in smooth muscle regeneration strategies. In 3D collagen hydrogels, we investigated whether sustained release of growth factors (GF) PDGF-AB and TGF-β1 from GF-loaded microspheres could induce a smooth muscle cell (SMC) phenotype in ASCs, and if the addition of uniaxial cyclic stretch could enhance the differentiation level. This study demonstrated that the combination of cyclic stretch and GF release over time from loaded microspheres potentiated the differentiation of ASCs, as quantified by protein expression of early to late SMC differentiation markers (SMA, TGLN and smooth muscle MHC). The delivery of GFs via microspheres produced large ASCs with a spindle-shaped, elongated SMC-like morphology. Cyclic strain produced the largest, longest, and most spindle-shaped cells regardless of the presence or absence of growth factors or the growth factor delivery method. Protein expression and cell morphology data confirmed that the sustained release of GFs from GF-loaded microspheres can be used to promote the differentiation of ASCs into SMCs and that the addition of uniaxial cyclic stretch significantly enhances the differentiation level, as quantified by intermediate and late SMC markers and a SMC-like elongated cell morphology.


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