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 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 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.

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 Cytokine, Chemokine, and Growth Factor Profile Characterization of Undifferentiated and Osteoinduced Human Adipose-Derived Stem Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
F. Mussano ◽  
T. Genova ◽  
M. Corsalini ◽  
G. Schierano ◽  
F. Pettini ◽  
...  
Keyword(s):  
Stem Cells ◽  
Growth Factors ◽  
Growth Factor ◽  
Expression Profile ◽  
Conditioned Media ◽  
High Expression ◽  
Adipose Derived Stem Cells ◽  
Osteogenic Medium ◽  
Cell Models

Bone is the second most manipulated tissue after blood. Adipose-derived stem cells (ASCs) may become a convenient source of MSC for bone regenerative protocols. Surprisingly, little is known about the most significant biomolecules these cells produce and release after being osteoinduced. Therefore, the present study aimed at dosing 13 candidates chosen among the most representative cytokines, chemokines, and growth factors within the conditioned media of osteodifferentiated and undifferentiated ASCs. Two acknowledged osteoblastic cell models, that is, MG-63 and SaOs-2 cells, were compared. Notably, IL-6, IL-8, MCP-1, and VEGF were highly produced and detectable in ASCs. In addition, while IL-6 and IL-8 seemed to be significantly induced by the osteogenic medium, no such effect was seen for MCP-1 and VEGF. Overall SaOS-2 had a poor expression profile, which may be consistent with the more differentiated phenotype of SaOs-2 compared to ASCs and MG-63. Instead, in maintaining medium, MG-63 displayed a very rich production of IL-12, MCP-1, IP-10, and VEGF, which were significantly reduced in osteogenic conditions, with the only exception of MCP-1. The high expression of MCP-1 and VEGF, even after the osteogenic commitment, may support the usage of ASCs in bone regenerative protocols by recruiting both osteoblasts and osteoclasts of the host.

scholarly journals The Antimicrobial Peptide Human β-Defensin-3 Accelerates Wound Healing by Promoting Angiogenesis, Cell Migration, and Proliferation Through the FGFR/JAK2/STAT3 Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Miho Takahashi ◽  
Yoshie Umehara ◽  
Hainan Yue ◽  
Juan Valentin Trujillo-Paez ◽  
Ge Peng ◽  
...  
Keyword(s):  
Wound Healing ◽  
Cell Migration ◽  
Growth Factors ◽  
Growth Factor ◽  
Antimicrobial Peptide ◽  
Fibroblast Growth Factor ◽  
Human Fibroblasts ◽  
Janus Kinase ◽  
Fibroblast Growth ◽  
Angiogenic Growth Factors

In addition to its antimicrobial activity, the skin-derived antimicrobial peptide human β-defensin-3 (hBD-3) promotes keratinocyte proliferation and migration to initiate the wound healing process; however, its effects on fibroblasts, which are the major cell type responsible for wound healing, remain unclear. We investigated the role of hBD-3 in cell migration, proliferation and production of angiogenic growth factors in human fibroblasts and evaluated the in vivo effect of hBD-3 on promoting wound healing and angiogenesis. Following hBD-3 treatment, the mouse wounds healed faster and showed accumulation of neutrophils and macrophages in the early phase of wound healing and reduction of these phagocytes 4 days later. hBD-3-treated wounds also displayed an increased number of fibroblasts and newly formed vessels compared to those of the control mice. Furthermore, the expression of various angiogenic growth factors was increased in the hBD-3-treated wounds. Additionally, in vitro studies demonstrated that hBD-3 enhanced the secretion of angiogenic growth factors such as fibroblast growth factor, platelet-derived growth factor and vascular endothelial growth factor and induced the migration and proliferation of human fibroblasts. The hBD-3-mediated activation of fibroblasts involves the fibroblast growth factor receptor 1 (FGFR1)/Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathways, as evidenced by the inhibitory effects of pathway-specific inhibitors. We indeed confirmed that hBD-3 enhanced the phosphorylation of FGFR1, JAK2 and STAT3. Collectively, the current study provides novel evidence that hBD-3 might be a potential candidate for the treatment of wounds through its ability to promote wound healing, angiogenesis and fibroblast activation.

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