scholarly journals Maintenance of a Schwann-Like Phenotype in Differentiated Adipose-Derived Stem Cells Requires the Synergistic Action of Multiple Growth Factors

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Alice E. Mortimer ◽  
Alessandro Faroni ◽  
Mahmut A. Kilic ◽  
Adam J. Reid
Keyword(s):  
Stem Cells ◽  
Growth Factors ◽  
Growth Factor ◽  
Growth Medium ◽  
Cell Morphology ◽  
Synergistic Action ◽  
Adipose Derived Stem Cells ◽  
Glial Growth Factor ◽  
Stimulating Factor

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adipose-derived stem cells (ASCs) towards Schwann cells produces an unstable phenotype when stimulating factors are withdrawn.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 Following ASC differentiation to Schwann-like cells, stimulating factors were withdrawn such that cells either remained in media supplemented with all stimulating factors, GGF-2 alone, or underwent complete withdrawal of all factors.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.

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 ◽  
...  
Keyword(s):  
Stem Cells ◽  
Growth Factors ◽  
Growth Factor ◽  
Keratinocyte Growth Factor ◽  
Adipogenic Differentiation ◽  
Growth Factor Signaling ◽  
Adipose Derived Stem Cells ◽  
Transient Activation ◽  
Neuropilin 1

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.

scholarly journals Controlled Growth Factor Delivery and Cyclic Stretch Induces a Smooth Muscle Cell-Like Phenotype in Adipose-Derived Stem Cells

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3123
Author(s):  
Brandan Walters ◽  
Paul A. Turner ◽  
Bernd Rolauffs ◽  
Melanie L. Hart ◽  
Jan P. Stegemann
Keyword(s):  
Stem Cells ◽  
Smooth Muscle ◽  
Growth Factors ◽  
Growth Factor ◽  
Sustained Release ◽  
Smooth Muscle Cell ◽  
Cell Morphology ◽  
Cyclic Stretch ◽  
Adipose Derived Stem Cells ◽  
Growth Factor Delivery

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.

scholarly journals Cyclophosphamide, Doxorubicin, Vincristine, Prednisone Dose Intensification With Granulocyte Colony-Stimulating Factor Markedly Depletes Stem Cell Reserve for Autologous Bone Marrow Transplantation

Blood ◽  
1997 ◽  
Vol 90 (12) ◽  
pp. 4996-5001 ◽  
Author(s):  
Arnold Freedman ◽  
Donna Neuberg ◽  
Peter Mauch ◽  
John Gribben ◽  
Robert Soiffer ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Growth Factors ◽  
Growth Factor ◽  
Standard Dose ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Dose Intensification ◽  
Sequential Trials ◽  
Stimulating Factor

Abstract Hematopoietic growth factors allow dose escalation of chemotherapy. This approach may potentially reduce the quality and quantity of hematopoietic stem cells. The capacity of stem cells recovered after dose intensification to support myeloablative therapy is unknown. In patients with previously untreated advanced follicular lymphoma, trilineage hematopoietic engraftment was compared in two sequential trials of induction therapy (standard dose cyclophosphamide, doxorubicin, vincristine, prednisone [CHOP] without growth factors or dose intensification CHOP supported by granulocyte colony-stimulating factor [G-CSF ]) followed by identical myeloablative therapy and autologous stem cell support. Neutrophil, platelet, and red blood cell (RBC) engraftment were compared on days 100, 180, and 360 after stem cell reinfusion. Despite similar patient characteristics including reinfusion of comparable numbers of marrow mononuclear cells, after stem cell transplantation, a highly significant prolongation of neutrophil and platelet engraftment was seen in patients who received high dose CHOP and G-CSF in comparison to standard dose CHOP. These findings suggest that dose intensified chemotherapy and G-CSF recruited stem cells into a proliferative phase and that G-CSF allowed retreatment at a time when stem cells were susceptible to damage by cytotoxic therapy. Such inadequate hematologic engraftment after myeloablative therapy might be avoided by either shortening the time that growth factor support is administered, lengthening the interval between cycles, or attempting to repetitively harvest additional stem cells either from the marrow or peripheral blood. Therefore, intensification of chemotherapy with growth factor support must be used with caution if stem cells are to be used to support myeloablative therapy.

scholarly journals Regulation of Cell Growth

1987 ◽  
Vol 80 (9) ◽  
pp. 591-593
Author(s):  
A J Barrett
Keyword(s):  
Stem Cells ◽  
Growth Factors ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Cell Growth ◽  
Cell Lines ◽  
Growth Regulation ◽  
Platelet Derived Growth Factor ◽  
Haemopoietic Stem Cells

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.

Apoptosis in the haemopoietic system

1994 ◽  
Vol 345 (1313) ◽  
pp. 257-263 ◽  
Keyword(s):  
Stem Cells ◽  
Growth Factors ◽  
Growth Factor ◽  
Cell Survival ◽  
Lineage Differentiation ◽  
Haemopoietic Stem Cells ◽  
Underlying Causes ◽  
Membrane Bound ◽  
Survival Signals

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.

scholarly journals Chemokines and Growth Factors Produced by Lymphocytes in the Incompetent Great Saphenous Vein

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Ewa Grudzińska ◽  
Sławomir Grzegorczyn ◽  
Zenon P. Czuba
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Saphenous Vein ◽  
Oscillatory Flow ◽  
Great Saphenous Vein ◽  
Upper Limbs ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Stimulating Factor

The role of cytokines in the pathogenesis of chronic venous disease (CVD) remains obscure. It has been postulated that oscillatory flow present in incompetent veins causes proinflammatory changes. Our earlier study confirmed this hypothesis. This study is aimed at assessing chemokines and growth factors (GFs) released by lymphocytes in patients with great saphenous vein (GSV) incompetence. In 34 patients exhibiting reflux in GSV, blood was derived from the cubital vein and from the incompetent saphenofemoral junction. In 12 healthy controls, blood was derived from the cubital vein. Lymphocyte culture with and without stimulation by phytohemagglutinin (PHA) was performed. Eotaxin, interleukin 8 (IL-8), macrophage inflammatory protein 1 A and 1B (MIP-1A and MIP-1B), interferon gamma-induced protein (IP-10), monocyte chemoattractant protein-1 (MCP-1), interleukin 5 (IL-5), fibroblast growth factor (FGF), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), platelet-derived growth factor-BB (PDGF-BB), and vascular endothelial growth factor (VEGF) were assessed in culture supernatants by a Bio-Plex assay. Higher concentrations of eotaxin and G-CSF were revealed in the incompetent GSV, compared with the concentrations in the patients’ upper limbs. The concentrations of MIP-1A and MIP-1B were higher in the CVD group while the concentration of VEGF was lower. In the stimulated cultures, the concentration of G-CSF proved higher in the incompetent GSV, as compared with the patients’ upper limbs. Between the groups, the concentration of eotaxin was higher in the CVD group, while the IL-5 and MCP-1 concentrations were lower. IL-8, IP-10, FGF, GM-CSF, and PDGF-BB did not reveal any significant differences in concentrations between the samples. These observations suggest that the concentrations of chemokines and GFs are different in the blood of CVD patients. The oscillatory flow present in incompetent veins may play a role in these changes. However, the role of cytokines in CVD requires further study.

scholarly journals Cardiac regeneration by pharmacologically active microcarriers releasing growth factors and/or transporting adipose-derived stem cells

2014 ◽  
Vol 87 (1) ◽  
Author(s):  
Monia Savi ◽  
Leonardo Bocchi ◽  
Emanuela Fiumana ◽  
Caterina Frati ◽  
Francesca Bonafé ◽  
...  
Keyword(s):  
Stem Cells ◽  
Growth Factors ◽  
Growth Factor ◽  
Cardiac Mechanics ◽  
Cardiac Regeneration ◽  
Physical Interaction ◽  
Adipose Derived Stem Cells ◽  
Old Myocardial Infarction ◽  
Pharmacologically Active ◽  
Hepatocyte Growth

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.

Adipose-Derived Stem Cells Improve the Aging Skin of Nude Mice by Promoting Angiogenesis and Reducing Local Tissue Water

2021 ◽  
Author(s):  
Feng Qin ◽  
Wenchao Zhang ◽  
Mingzi Zhang ◽  
Xiao Long ◽  
Loubin Si ◽  
...  
Keyword(s):  
Stem Cells ◽  
Growth Factors ◽  
Growth Factor ◽  
Nude Mice ◽  
Blood Perfusion ◽  
Adipose Derived Stem Cells ◽  
Angiogenic Growth Factors ◽  
Tissue Water ◽  
Skin Rejuvenation ◽  
Aging Skin

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.

scholarly journals Cyclophosphamide, Doxorubicin, Vincristine, Prednisone Dose Intensification With Granulocyte Colony-Stimulating Factor Markedly Depletes Stem Cell Reserve for Autologous Bone Marrow Transplantation

Blood ◽  
1997 ◽  
Vol 90 (12) ◽  
pp. 4996-5001 ◽  
Author(s):  
Arnold Freedman ◽  
Donna Neuberg ◽  
Peter Mauch ◽  
John Gribben ◽  
Robert Soiffer ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Growth Factors ◽  
Growth Factor ◽  
Standard Dose ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Dose Intensification ◽  
Sequential Trials ◽  
Stimulating Factor

Hematopoietic growth factors allow dose escalation of chemotherapy. This approach may potentially reduce the quality and quantity of hematopoietic stem cells. The capacity of stem cells recovered after dose intensification to support myeloablative therapy is unknown. In patients with previously untreated advanced follicular lymphoma, trilineage hematopoietic engraftment was compared in two sequential trials of induction therapy (standard dose cyclophosphamide, doxorubicin, vincristine, prednisone [CHOP] without growth factors or dose intensification CHOP supported by granulocyte colony-stimulating factor [G-CSF ]) followed by identical myeloablative therapy and autologous stem cell support. Neutrophil, platelet, and red blood cell (RBC) engraftment were compared on days 100, 180, and 360 after stem cell reinfusion. Despite similar patient characteristics including reinfusion of comparable numbers of marrow mononuclear cells, after stem cell transplantation, a highly significant prolongation of neutrophil and platelet engraftment was seen in patients who received high dose CHOP and G-CSF in comparison to standard dose CHOP. These findings suggest that dose intensified chemotherapy and G-CSF recruited stem cells into a proliferative phase and that G-CSF allowed retreatment at a time when stem cells were susceptible to damage by cytotoxic therapy. Such inadequate hematologic engraftment after myeloablative therapy might be avoided by either shortening the time that growth factor support is administered, lengthening the interval between cycles, or attempting to repetitively harvest additional stem cells either from the marrow or peripheral blood. Therefore, intensification of chemotherapy with growth factor support must be used with caution if stem cells are to be used to support myeloablative therapy.

scholarly journals Deciphering the role of substrate stiffness in enhancing the internalization efficiency of plasmid DNA in stem cells using lipid-based nanocarriers

Nanoscale ◽  
2018 ◽  
Vol 10 (19) ◽  
pp. 8947-8952 ◽  
Author(s):  
Saman Modaresi ◽  
Settimio Pacelli ◽  
Jonathan Whitlow ◽  
Arghya Paul
Keyword(s):  
Stem Cells ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Plasmid Dna ◽  
Substrate Stiffness ◽  
Vascular Endothelial ◽  
Adipose Derived Stem Cells ◽  
Endothelial Growth Factor ◽  
Viral Transfection

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).

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