The Paracrine Effect of Adipose-Derived Stem Cells Orchestrates Competition between Different Damaged Dermal Fibroblasts to Repair UVB-Induced Skin Aging

Background. Human dermal fibroblasts (HDFs) are the primary cells in skin and are associated with UVB-induced skin photoaging. Adipose-derived stem cells (ASCs) have been proposed as a treatment for skin aging. The goal of this study was to investigate paracrine mechanisms by which ASCs repair HDFs damage from UVB exposure. Methods. ASCs were cocultured with UVB-irradiated and nonirradiated HDFs. We compared HDF senescence, proliferation, migration, oxidative stress, and cytokine expression. In a nude mouse UVB-induced photoaging model, ASCs were injected subcutaneously, and skin samples were collected weekly between postoperative weeks 3 through 7. Histological analysis, PCR, ELISA, and immunohistochemistry were used to analyze the effect of ASCs. Results. Compared with UVB-irradiated HDFs, nonirradiated HDFs showed higher proliferation and migration, reduced apoptosis, and fewer senescent cells when cocultured with ASCs. The expression of extracellular matrix-related cytokines was also regulated by ASCs. In addition, ASCs effectively reversed UVB-induced skin photoaging in vivo. We propose that ASCs more robustly coordinate healthy HDFs than UVB-damaged HDFs to repair aging skin. Conclusions. ASCs improved the function of both UVB-damaged and healthy HDFs through paracrine effects. However, the impact of ASCs on healthy HDFs was greater than UVB-damaged HDFs. These findings help to elucidate the underlying mechanisms of the skin rejuvenation effect of ASCs.

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Paracrine Effects of Adipose-Derived Stem Cells on Keratinocytes and Dermal Fibroblasts

Annals of Dermatology ◽

10.5021/ad.2012.24.2.136 ◽

2012 ◽

Vol 24 (2) ◽

pp. 136 ◽

Cited By ~ 105

Author(s):

Seung Ho Lee ◽

Sang Yun Jin ◽

Jin Seok Song ◽

Kyle K. Seo ◽

Kwang Hyun Cho

Keyword(s):

Stem Cells ◽

Dermal Fibroblasts ◽

Adipose Derived Stem Cells ◽

Paracrine Effects

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HB-EGF Improves the Hair Regenerative Potential of Adipose-Derived Stem Cells via ROS Generation and Hck Phosphorylation

International Journal of Molecular Sciences ◽

10.3390/ijms21010122 ◽

2019 ◽

Vol 21 (1) ◽

pp. 122 ◽

Cited By ~ 4

Author(s):

Nahyun Choi ◽

Won-Serk Kim ◽

Sang Ho Oh ◽

Jong-Hyuk Sung

Keyword(s):

Stem Cells ◽

Growth Factor ◽

Hair Growth ◽

Ros Generation ◽

Adipose Derived Stem Cells ◽

Heparin Binding ◽

Dermal Papilla Cells ◽

Self Renewal ◽

Paracrine Effects

Although adipose-derived stem cells (ASCs) have hair regenerative potential, their hair inductive capabilities are limited. The mitogenic and hair inductive effects of heparin binding-epidermal growth factor-like growth factor (HB-EGF) on ASCs were investigated in this study and the underlying mechanism of stimulation was examined. Cell growth, migration, and self-renewal assays, as well as quantitative polymerase chain reactions and immunostaining, were carried out. Telogen-to-anagen transition and organ culture using vibrissa follicles were also conducted. HB-EGF significantly increased ASC motility, including cell proliferation, migration, and self-renewal activity. The preconditioning of ASCs with HB-EGF induced telogen-to-anagen transition more rapidly in vivo, and injected PKH26-ASCs survived for longer periods of time. Conditioned medium obtained from HB-EGF-treated ASCs promoted hair growth in vivo, upregulating growth factors. In particular, thrombopoietin (THPO) also induced hair growth in vivo, stimulating dermal papilla cells (DPCs). Reactive oxygen species (ROS) appeared to play a key role in ASC stimulation as the inhibition of ROS generation and NOX4 knockout attenuated ASC stimulation and THPO upregulation by HB-EGF. In addition, the Hck phosphorylation pathway mediated the stimulation of ASCs by HB-EGF. In summary, HB-EGF increased the motility and paracrine effects of ASCs releasing THPO growth factor and THPO promoted hair growth-stimulating DPCs. ROS generation and Hck phosphorylation are key factors in HB-EGF-induced ASC stimulation. Therefore, combination therapy involving HB-EGF and ASCs may provide a novel solution for hair-loss treatment.

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Oncogenic Linear Collagen VI of Invasive Breast Cancer Is Induced by CCL5

Journal of Clinical Medicine ◽

10.3390/jcm9040991 ◽

2020 ◽

Vol 9 (4) ◽

pp. 991 ◽

Cited By ~ 2

Author(s):

Elizabeth Brett ◽

Matthias Sauter ◽

Éadaoin Timmins ◽

Omid Azimzadeh ◽

Michael Rosemann ◽

...

Keyword(s):

Stem Cells ◽

Extracellular Matrix ◽

Potential Role ◽

Dermal Fibroblasts ◽

Adipose Derived Stem Cells ◽

Mechanism Of Formation ◽

Collagen Vi

The triple-negative breast tumor boundary is made of aligned, linear collagen. The pro-oncogenic impact of linear collagen is well established; however, its mechanism of formation is unknown. An in vitro analogue of the tumor border is created by a co-culture of MDA-MB-231 cells, adipose derived stem cells, and dermal fibroblasts. Decellularization of this co-culture after seven days reveals an extracellular matrix that is linear in fashion, high in pro-oncogenic collagen type VI, and able to promote invasion of reseeded cells. Further investigation revealed linear collagen VI is produced by fibroblasts in response to a paracrine co-culture of adipose derived stem cells and MDA-MB-231, which together secrete high levels of the chemokine CCL5. The addition of monoclonal antibody against CCL5 to the co-culture results in an unorganized matrix with dramatically decreased collagen VI. Importantly, reseeded cells do not exhibit pro-oncogenic behavior. These data illustrate a cellular mechanism, which creates linear extracellular matrix (ECM) in vitro, and highlight a potential role of CCL5 for building striated tumor collagen in vivo.

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Effect of Pig-Adipose-Derived Stem Cells’ Conditioned Media on Skin Wound-Healing Characteristics In Vitro

International Journal of Molecular Sciences ◽

10.3390/ijms22115469 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5469

Author(s):

Joanna Wiśniewska ◽

Magda Słyszewska ◽

Karolina Stałanowska ◽

Katarzyna Walendzik ◽

Marta Kopcewicz ◽

...

Keyword(s):

Stem Cells ◽

Wound Healing ◽

Three Dimensional ◽

Dermal Fibroblasts ◽

Conditioned Media ◽

Adipose Derived Stem Cells ◽

Skin Wound Healing ◽

Cell Functions ◽

The Impact

The primary mechanism by which adipose-derived stem cells (ASCs) exert their reparative or regenerative potential relies predominantly on paracrine action. Secretory abilities of ASCs have been found to be amplified by hypoxia pre-conditioning. This study investigates the impact of hypoxia (1% O2) on the secretome composition of pig ASCs (pASCs) and explores the effect of pASCs’ conditioned media (CM) on skin cell functions in vitro and the expression of markers attributed to wound healing. Exposure of pASCs to hypoxia increased levels of vascular endothelial growth factor (VEGF) in CM-Hyp compared to CM collected from the cells cultured in normoxia (CM-Nor). CM-Hyp promoted the migratory ability of pig keratinocytes (pKERs) and delayed migration of pig dermal fibroblasts (pDFs). Exposure of pKERs to either CM-Nor or CM-Hyp decreased the levels of pro-fibrotic indicators WNT10A and WNT11. Furthermore, CM-Hyp enhanced the expression of KRT14, the marker of the basal epidermis layer. In contrast, CM-Nor showed a stronger effect on pDFs manifested by increases in TGFB1, COL1A1, COL3A1, and FN1 mRNA expression. The formation of three-dimensional endothelial cell networks was improved in the presence of CM-Hyp. Overall, our results demonstrate that the paracrine activity of pASCs affects skin cells, and this property might be used to modulate wound healing.

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Stamina-Enhancing Effects of Human Adipose-Derived Stem Cells

Cell Transplantation ◽

10.1177/09636897211035409 ◽

2021 ◽

Vol 30 ◽

pp. 096368972110354

Author(s):

Eun-Jung Yoon ◽

Hye Rim Seong ◽

Jangbeen Kyung ◽

Dajeong Kim ◽

Sangryong Park ◽

...

Keyword(s):

Physical Activity ◽

Stem Cells ◽

Locomotor Activity ◽

Tissue Injury ◽

Male Rats ◽

Adipose Derived Stem Cells ◽

Sprague Dawley ◽

Serum Triglycerides

Stamina-enhancing effects of human adipose derived stem cells (hADSCs) were investigated in young Sprague-Dawley rats. Ten-day-old male rats were transplanted intravenously (IV) or intracerebroventricularly (ICV) with hADSCs (1 × 106 cells/rat), and physical activity was measured by locomotor activity and rota-rod performance at post-natal day (PND) 14, 20, 30, and 40, as well as a forced swimming test at PND 41. hADSCs injection increased the moving time in locomotor activity, the latency in rota-rod performance, and the maximum swimming time. For the improvement of physical activity, ICV transplantation was superior to IV injection. In biochemical analyses, ICV transplantation of hADSCs markedly reduced serum creatine phosphokinase, lactate dehydrogenase, alanine transaminase, and muscular lipid peroxidation, the markers for muscular and hepatic injuries, despite the reduction in muscular glycogen and serum triglycerides as energy sources. Notably, hADSCs secreted brain-derived neurotrophic factor (BDNF) and nerve growth factor in vitro, and increased the level of BDNF in the brain and muscles in vivo. The results indicate that hADSCs enhance physical activity including stamina not only by attenuating tissue injury, but also by strengthening the muscles via production of BDNF.

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Elimination of Reperfusion-Induced Microcirculatory Alterations In Vivo by Adipose-Derived Stem Cell Supernatant without Adipose-Derived Stem Cells

Plastic & Reconstructive Surgery ◽

10.1097/prs.0000000000001097 ◽

2015 ◽

Vol 135 (4) ◽

pp. 1056-1064 ◽

Cited By ~ 7

Author(s):

Wei Z. Wang ◽

Xin-Hua Fang ◽

Shelley J. Williams ◽

Linda L. Stephenson ◽

Richard C. Baynosa ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Adipose Derived Stem Cells ◽

Adipose Derived Stem Cell ◽

Cell Supernatant

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Establishment and Identification of a CiPSC Lineage Reprogrammed from FSP-tdTomato Mouse Embryonic Fibroblasts (MEFs)

Stem Cells International ◽

10.1155/2018/5965727 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 3

Author(s):

Ruiping Chen ◽

Wenxiu Xie ◽

Baomei Cai ◽

Yue Qin ◽

Chuman Wu ◽

...

Keyword(s):

Stem Cells ◽

Small Molecule ◽

Fluorescent Protein ◽

Day Treatment ◽

Tracking System ◽

Embryonic Stem ◽

Mouse Embryonic Fibroblasts ◽

Embryonic Fibroblasts ◽

Underlying Mechanisms

Safety issues associated with transcription factors or viruses may be avoided with the use of chemically induced pluripotent stem cells (CiPSCs), thus promoting their clinical application. Previously, we had successfully developed and standardized an induction method using small-molecule compound, with simple operation, uniform induction conditions, and clear constituents. In order to verify that the CiPSCs were indeed reprogrammed from mouse embryonic fibroblasts (MEFs), and further explore the underlying mechanisms, FSP-tdTomato mice were used to construct a fluorescent protein-tracking system of MEFs, for revealing the process of CiPSC reprogramming. CiPSCs were identified by morphological analysis, mRNA, and protein expression of pluripotency genes, as well as teratoma formation experiments. Results showed that after 40-day treatment of tdTomato-MEFs with small-molecule compounds, the cells were presented with prominent nucleoli, high core-to-cytoplasmic ratio, round shape, group and mass arrangement, and high expression of pluripotency gene. These cells could differentiate into three germ layer tissues in vivo. As indicated by the above results, tdTomato-MEFs could be reprogrammed into CiPSCs, a lineage that possesses pluripotency similar to mouse embryonic stem cells (mESCs), with the use of small-molecule compounds. The establishment of CiPSC lineage, tracked by fluorescent protein, would benefit further studies exploring its underlying mechanisms. With continuous expression of fluorescent proteins during cellular differentiation, this cell lineage could be used for tracking CiPSC transplantation and differentiation into functional cells.

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High glucose induces early senescence in adipose-derived stem cells by accelerating p16 and mTOR

Biomedical Research and Therapy ◽

10.15419/bmrat.v6i6.548 ◽

2019 ◽

Vol 6 (6) ◽

pp. 3213-3221

Author(s):

Hieu Liem Pham ◽

Phuc Van Pham

Keyword(s):

Stem Cells ◽

High Glucose ◽

Glucose Concentration ◽

Culture Medium ◽

Diabetic Patients ◽

Adipose Derived Stem Cells ◽

Differentiation Potential ◽

Normal Glucose

Introduction: The senescence of stem cells is the primary reason that causes aging of stem cell-containing tissues. Some hypotheses have suggested that high glucose concentration in diabetic patients is the main factor that causes senescence of cells in those patients. This study aimed to evaluate the effects of high glucose concentrations on the senescence of adipose-derived stem cells (ADSCs). Methods: ADSCs were isolated and expanded from human adipose tissues. They were characterized and confirmed as mesenchymal stem cells (MSCs) by expression of surface markers, their shape, and in vitro differentiation potential. They were then cultured in 3 different media- that contained 17.5 mM, 35 mM, or 55 mM of D-glucose. The senescent status of ADSCs was recorded by the expression of the enzyme beta-galactosidase, cell proliferation, and doubling time. Real-time RT-PCR was used to evaluate the expression of p16, p21, p53 and mTOR. Results: The results showed that high glucose concentrations (35 mM and 55 mM) in the culture medium induced senescence of human ADSCs. The ADSCs could progress to the senescent status quicker than those cultured in the lower glucose-containing medium (17.5 mM). The senescent state was related to the up-regulation of p16 and mTOR genes. Conclusion: These results suggest that high glucose in culture medium can trigger the expression of p16 and mTOR genes which cause early senescence in ADSCs. Therefore, ADSCs should be cultured in low glucose culture medium, or normal glucose concentration, to extend their life in vitro as well as in vivo.

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