Hair growth stimulated by conditioned medium of adipose-derived stem cells is enhanced by hypoxia: evidence of increased growth factor secretion

Park, Byung-Soon; Kim, Won‐Serk; Choi, Joon-Seok; Kim, Hyung-Ki; Won, Jong-Hyun; Ohkubo, Fumio; Fukuoka, Hirotaro

doi:10.2220/biomedres.31.27

Cited by 149 publications

(131 citation statements)

References 30 publications

(27 reference statements)

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“…For example, Rehman et al reported that hypoxia increased antiapoptotic and angiogenic growth factor secretion of ASC, which increased the recovery from hind-limb ischemia [11]. Our group also demonstrated that hypoxia-expanded ASCs enhanced antioxidant and angiogenic growth factor secretion to accelerate skin regeneration [8,9]. However, all those studies focused on the chronic response to hypoxia whereby stabilization of HIF-1a enhanced the secretion of target proteins and increased the regenerative potential of ASCs.…”

Section: Introductionmentioning

confidence: 59%

“…In those studies, the treatment of a conditioned medium of ASCs (ASC-CM) stimulated dermal fibroblasts and papilla cells, and ASC transplantation accelerated wound healing and hair regeneration in vivo. Of note, the hypoxia-cultured ASCs and CM induced a significant increase in wound-healing and hairgrowth potential compared with normal culture conditions [8,9]. Likewise, the beneficial effects of culturing ASC under hypoxic conditions has been reported in various experimental systems [10][11][12][13][14].…”

Section: Introductionmentioning

confidence: 86%

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The Pivotal Role of Reactive Oxygen Species Generation in the Hypoxia-Induced Stimulation of Adipose-Derived Stem Cells

Kim

Park

et al. 2011

Stem Cells and Development

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Adipose-derived stem cells (ASCs) offer a potential alternative for tissue repair and regeneration. We have recently shown that hypoxia stimulates ASCs and enhances the regenerative potential of ASCs, which is beneficial for ASC therapy. In the present study, we further investigated a key mediator and a signal pathway involved in the stimulation of ASC during hypoxia. Culturing ASC in a hypoxic incubator (2% oxygen tension) increased the proliferation and migration, and this was mediated by Akt and ERK pathways. To determine the generation of reactive oxygen species (ROS), 2¢,7¢-dichlorofluorescin diacetate intensity was detected by fluorescence-activated cell sorting. Hypoxia significantly increased the dichlorofluorescin diacetate intensity, which was greatly reduced by N-acetyl-cysteine and diphenyleneiodonium treatment. Likewise, the hypoxia-induced proliferation and migration of ASCs were reversed by N-acetyl-cysteine and diphenyleneiodonium treatment, suggesting the involvement of ROS generation in ASC stimulation. Further, we examined the activation of receptor tyrosine kinases and observed that hypoxia stimulated the phosphorylation of platelet-derived growth factor receptor-b. In summary, the ROS produced by ASCs in response to hypoxia was mostly likely due to NADPH oxidase activity. The increased cellular ROS was accompanied by the phosphorylation of platelet-derived growth factor receptor-b as well as by the activation of ERK and Akt signal pathways. Our results suggest a pivotal role for ROS generation in the stimulation of ASCs by hypoxia.

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Section: Introductionmentioning

confidence: 59%

Section: Introductionmentioning

confidence: 86%

The Pivotal Role of Reactive Oxygen Species Generation in the Hypoxia-Induced Stimulation of Adipose-Derived Stem Cells

Kim

Park

et al. 2011

Stem Cells and Development

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“…The proliferation of adipose tissue-derived stem cells (ADSCs) is elevated under hypoxic conditions as compared to normoxic conditions. In this experimental model, hypoxia enhanced the ADSC-promoted hair growth via the production/ secretion of growth factors (29). The physiological condition of the bone marrow appears to be low in oxygen tension and limited in nutrient supply.…”

Section: Discussionmentioning

confidence: 80%

Intensified expressions of a monocarboxylate transporter in consistently renewing tissues of the mouse

2011

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Monocarboxylates-lactate and ketone bodies-can compensate for glucose as energy sources under certain physical conditions. To identify the main energy source used in self-renewing tissues, expression profiles of monocarboxylate transporters (MCTs) were mainly investigated immunohistochemically in the gastrointestinal tract, skin, and bone marrow of mice, with reference to glucose transporters. In the small intestine, MCT1-immunoreactive epithelial cells accumulated in crypts with a selective immunolabeling along the basolateral membrane of cells. BrdU-labeled dividing cells were included in the cryptal MCT1-immunoreactive foci. The skin displayed an intense and extensive immunoreactivity for MCT1 in the hair bulge, which gives rise to the epidermis, hair, and sebaceous gland. The stratified squamous epithelium in the esophagus contained MCT1-immunoreactive cells in the basal layer but frequently lacked GLUT1-immunoreactive cells. The bone marrow was largely immunoreactive for MCT1 but not for GLUT1, suggesting the active production and utilization of monocarboxylates for hematopoiesis under hypoxic conditions. These findings support the idea that monocarboxylates are favorite energy sources in self-renewing tissues.Mammals use two kinds of energy substrates, glucose and monocarboxylates. The latter includes lactate, acetate, ketone bodies, and others. These monocarboxylates, which are intermediate metabolites, provide a "ready-to-use" fuel in most cells or are converted into glucose (gluconeogenesis) and fatty acids (lipogenesis). They can compensate for glucose as an energy source under several physical conditions such as fasting, diabetes, and the neonatal period (16,35). The production of monocarboxylates does not need oxygen; therefore, they may be evolutionally older (more primitive) energy substrates than glucose, since the concentration of O 2 was low in ancient times. Hypoxic conditions exist in the bone marrow and tumors where proliferative activities are high, and some signals of hypoxia stimulate the cell proliferation (7, 9). There is a possibility that the monocarboxylates produced by anaerobic glycolysis are favorite energy sources for cell growth in selfrenewing tissues and tumors. In mammals, a membrane-bound transporter family mediates the uptake and excretion of monocarboxylates. A representative transporter for monocarboxylates is the monocarboxylate transporter (MCT) and the classified SLC16 gene family. MCT is a H + -coupled, electroneutral, and bi-directional transporter composed of twelve transmembrane domains with intracellular N and C terminal domains (10, 11). To date, fourteen MCT isoforms-each having a unique distribution and different sequence homology-have been identified in mammals, though only four (MCT1-MCT4) have been demonstrated experimentally to facilitate the proton-linked transport of metabolically important monocarboxylates (14,23). It is possible to evaluate the existence of a monocarbox-

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“…La siguiente alternativa planteada, siguiendo la lógica como sucede con la estimulación angiogénica y fibroblástica (17,18), es que exista estimulación por efecto paracrino hacia el linaje epidérmico mediante la secreción de factores de crecimiento como el EGF, IGF, PDGF, entre otros. Más aún, está documentado el crecimiento de pelo debido a la estimulación paracrina de las ASCs (19,20).…”

Section: Discussionunclassified

Epitelización inducida por células troncales derivadas del tejido adiposo

Meruane

Benítez

Rojas

et al. 2014

Cir. plást. iberolatinoam.

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ResumenEl tratamiento de lesiones con pérdida de tejido cutáneo ha mejorado notablemente con el advenimiento de la bioingeniería tisular. Una alternativa en desarrollo es la utilización de sustitutos dérmicos combinados con células troncales derivadas del tejido adiposo autó-logo. Estudios previos nos muestran que con esta técnica es posible optimizar la angiogénesis y la síntesis de colágeno, sin embargo potenciar la epitelización es un tema pendiente por resolver. En el presente estudio evaluamos la progresión y diferenciación epitelial en un período de tiempo prologando.Obtuvimos las células troncales a partir del tejido adiposo (ASC) de la región inguinal de 4 ratas Sprague Dawley. Cultivamos las cé-lulas frescas en una matriz de Integra ® durante un período total de 48 horas, y las marcamos con un vector lentiviral-GFP (proteína fluorescente verde). Posteriormente, injertamos en las mismas ratas la matriz dérmica con células troncales y un implante contralateral sin células, como control. A las 4 semanas, evaluamos el avance epitelial mediante planimetría de superficie e histología.Los resultados macroscópicos muestran que el cierre de la herida por contracción de los bordes no tiene diferencias significativas (82,63%±3,4% vs. 80,66%±3,89%; p=0,08), pero el cierre por epitelización fue significativamente mayor en el lado intervenido con ASCs (93,47%±5,98% vs. 79,88%±6,28%; p=0,0028). Todas las muestras obtuvieron tinción positiva para el anticuerpo anti-citoqueratina 34βE12 y el avance epitelial lineal cuantificado por microscopía resultó significativamente mayor en el lado con ASCs (6408±275µm vs. 5375±250µm; p<0,001). Identificamos las células GFP positivas formando parte de la dermis regenerada, no así en la epidermis.En conclusión, las células troncales derivadas del tejido adiposo autólogo sembradas en una matriz de Integra® aumentan la formación epitelial significativamente, probablemente por un mecanismo de inducción más que de diferenciación. Palabras clave Epitelio epidérmico, Células madre,Tejido adiposo, Sustituto dérmico, Ingeniería tisular. Nivel de evidencia científica II AbstractThe treatment of injuries with loss of skin tissue has improved significantly with the advent of bioengineered tissue. Previous studies showed that the use of dermal substitutes combined with autologous Adipose-derived Stem Cells (ASCs) improve angiogenesis and collagen synthesis; however, epithelialization is an outstanding issue to be resolved. In the present study, we evaluated the epithelial progression and differentiation in an extended period of time.We obtained the adipose tissue derived stem cells (ASCs) from the inguinal fat pad of 4 Sprague Dawley rats. The non-expanded cells were cultivated in a dermal scaffold (Integra®) for 48 hours and marked with a green fluorescent protein (GFP) lentiviral vector. The scaffold plus stem cells and a contralateral cell-free scaffold (control) were implanted in the same rats. After 4 weeks, epithelial surface was assesses by planimetry and histology.The results show that ...

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Hair growth stimulated by conditioned medium of adipose-derived stem cells is enhanced by hypoxia: evidence of increased growth factor secretion

Cited by 149 publications

References 30 publications

The Pivotal Role of Reactive Oxygen Species Generation in the Hypoxia-Induced Stimulation of Adipose-Derived Stem Cells

The Pivotal Role of Reactive Oxygen Species Generation in the Hypoxia-Induced Stimulation of Adipose-Derived Stem Cells

Intensified expressions of a monocarboxylate transporter in consistently renewing tissues of the mouse

Epitelización inducida por células troncales derivadas del tejido adiposo

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