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 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adipose-derived stem cells (ASCs) towards Schwann cells produces an unstable phenotype when stimulating factors are withdrawn.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 Following ASC differentiation to Schwann-like cells, stimulating factors were withdrawn such that cells either remained in media supplemented with all stimulating factors, GGF-2 alone, or underwent complete withdrawal of all factors.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 Human adipose-derived stem cells pre-treated with platelet-rich plasma and hepatocyte growth factor alleviate liver fibrosis in mice

2018 ◽  
Vol 5 (5) ◽  
pp. 2332-2348 ◽  
Author(s):  
Nam H. Nguyen ◽  
Trinh V. Le ◽  
Huy Q. Do ◽  
Thanh M. Dang ◽  
Yen K. T. Nguyen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Growth Factor ◽  
Liver Fibrosis ◽  
Hepatocyte Growth Factor ◽  
Platelet Rich Plasma ◽  
Smooth Muscle Actin ◽  
Mrna Levels ◽  
Adipose Derived Stem Cells ◽  
Healthy Human ◽  
Hepatocyte Growth

Background: Transplantation of adipose-derived stem cells (ADSCs) is a potential therapy for a variety of liver diseases. Previous studies have shown that ADSC-based therapy is promising for liver fibrosis treatment. Recently, many publications have suggested that pretreating ADSCs with growth factors before transplantation can elevate the effectiveness of the therapy. Therefore, we hypothesize that human ADSCs (hADSCs) pretreated with platelet-rich plasma (PRP) and hepatocyte growth factor (HGF), compared to ADSCs alone, would accelerate the treatment effects on liver fibrosis in mice. Methods: The hADSCs were cultured solely with conventional media, or with HGF (human recombinant; 20 ng/ml), or with HGF and PRP (from healthy human blood, 10%), concomitantly added to the medium for 7 days before transplantation. Eight-week-old male mice were treated with CCl4 (1 ml/kg) for 11 weeks to induce liver fibrosis. The mice were then subsequently divided into: 1) Placebo group (PBS injection); 2) ADSCs/HGF+PRP (5x105HGF and PRP pre-treated cells/mice); 3) ADSCs/HGF (5x105HGF pre-treated cells/mice) and 4) ADSCs (5x105non-pretreated cells/mice). Results: Seven days post-transplantation, the alanine transaminase (ALT) level in the placebo was notably elevated (143.10±14.96 IU/L), compared to ALT levels of ADSCs-, ADSCs/HGF+PR-, and ADSCs/HGF-transplanted mice, which showed an improvement (67.94±18.57 IU/L, 49.44±7.56 IU/L, and 57.93±5.75 IU/L, respectively). The procollagen-α1 and alpha-smooth muscle actin (α-SMA) mRNA levels were significantly down-regulated in the ADSCs-transplanted group compared to those of the placebo. Importantly, these levels were lower in ADSCs/HGF+PR (procollagen-α1: 75.64±45.89; α-SMA: 36.17±36.09) than those of ADSCs/HGF (procollagen-α1: 212.8±84.35; α-SMA: 52.41±7.93) and ADSCs only (procollagen-α1: 310.50 ± 55.36; α-SMA: 184.70±14.06). Stem cell transplantation also improved histological index, reducing inflammation and collagen/necrotic structure accumulation. However, there were no statistical differences between three ADSCs treatment groups after 14 days after transplantation. Conclusion: Pre-treatment with PRP and HGF for 7 days enhanced the efficacy of ADSCs in alleviating liver fibrosis in vivo.

Hepatocyte Growth Factor Secreted from Human Adipose-Derived Stem Cells Inhibits Fibrosis in Hypertrophic Scar Fibroblasts

2020 ◽  
Vol 20 (7) ◽  
pp. 558-571 ◽  
Author(s):  
Ji Ma ◽  
Xin Yan ◽  
Yue Lin ◽  
Qian Tan
Keyword(s):  
Stem Cells ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Hypertrophic Scar ◽  
Collagen Type ◽  
Smooth Muscle Actin ◽  
Adipose Derived Stem Cells ◽  
Collagen Production ◽  
Rabbit Ear ◽  
Hepatocyte Growth

Aims: To study the effect of Adipose-derived stem cells (ADSCs) on fibrosis of hypertrophic scar-derived fibroblasts (HSFs) and its concrete mechanism. Background: ADSCs have been reported to reduce collagen production and fibroblast proliferation in co-culture experiments. Conditioned medium from adipose-derived stem cells (ADSCs-CM) has successfully inhibited fibrosis by decreasing the expression of collagen type І (Col1) and α-smooth muscle actin (α-SMA) in rabbit ear scar models. Hepatocyte growth factor (HGF), the primary growth factor in ADSCs-CM, has been shown to reverse fibrosis in various fibrotic diseases. Background: ADSCs have been reported to reduce collagen production and fibroblast proliferation in co-culture experiments. Conditioned medium from adipose-derived stem cells (ADSCs-CM) has successfully inhibited fibrosis by decreasing the expression of collagen type І (Col1) and α-smooth muscle actin (α-SMA) in rabbit ear scar models. Hepatocyte growth factor (HGF), the primary growth factor in ADSCs-CM, has been shown to reverse fibrosis in various fibrotic diseases. Objective: To test the hypothesis that ADSCs inhibit fibrosis of HSFs through the secretion of HGF. Methods: HSFs were treated with DMEM containing 0%, 10%, 50% and 100% concentration of ADSCs-CM. The effect of ADSCs-CM on the viability was determined by cell viability assay, and the collagen production in HSFs was examined by Sirius red staining. Expression and secretion of fibrosis and degradation proteins were detected separately. After measuring the concentration of HGF in ADSCs-CM, the same number of HSFs were treated with 50% ADSCs-CM or HGF. HGF activity in ADSCs-CM was neutralized with a goat anti-human HGF antibody. Results: The results demonstrated that ADSCs-CM dose-dependently decreased cell viability, expression of fibrosis molecules, and tissue inhibitor of metalloproteinases-1 (TIMP-1), and significantly increased matrix metalloproteinase-1 (MMP-1) expression in HSFs. Collagen production and the ratio of collagen type І and type III (Col1/Col3) were also suppressed by ADSCs-CM in a dose-dependent manner. When HSFs were cultured with either 50% ADSCs-CM or HGF (1 ng/ml), a similar trend was observed in gene expression and protein secretion. Adding an HGF antibody to both groups returned protein expression and secretion to basal levels but did not significantly affect the fibrosis factors in the control group. Conclusion: Our findings revealed that adipose-derived stem cell-secreted HGF effectively inhibits fibrosis-related factors and regulates extracellular matrix (ECM) remodeling in hypertrophic scar fibroblasts.

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 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.

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