Human adipose-derived stem cells: current challenges and clinical perspectives

Adult or somatic stem cells hold great promise for tissue regeneration. Currently, one major scientific interest is focused on the basic biology and clinical application of mesenchymal stem cells. Adipose tissue-derived stem cells share similar characteristics with bone marrow mesenchymal stem cells, but have some advantages including harvesting through a less invasive surgical procedure. Moreover, adipose tissue-derived stem cells have the potential to differentiate into cells of mesodermal origin, such as adipocytes, cartilage, bone, and skeletal muscle, as well as cells of non-mesodermal lineage, such as hepatocytes, pancreatic endocrine cells, neurons, cardiomyocytes, and vascular endothelial cells. There are, however, inconsistencies in the scientific literature regarding methods for harvesting adipose tissue and for isolating, characterizing and handling adipose tissue-derived stem cells. Future clinical applications of adipose tissue-derived stem cells rely on more defined and widespread methods for obtaining cells of clinical grade quality. In this review, current methods in adipose tissue-derived stem cell research are discussed with emphasis on strategies designed for future applications in regenerative medicine and possible challenges along the way.As células-tronco adultas ou somáticas detêm grande promessa para a reparação e regeneração de tecidos. Atualmente, o interesse dos cientistas é contínuo na investigação da biologia de células-tronco mesenquimais, tanto em aspectos básicos, quanto no potencial de aplicações terapêuticas. As células-tronco adultas derivadas do estroma do tecido adiposo, em comparação com as células-tronco derivadas do estroma da medula óssea, apresentam como vantagem o método fácil de obtenção da fonte tecidual. As células-tronco adultas derivadas do estroma do tecido adiposo apresentam potencial para se diferenciarem em células de tecidos mesodérmicos, como os adipócitos, as cartilagens, os ossos e o músculo esquelético e não mesodérmicos, como os hepatócitos, as células pancreáticas endócrinas, os neurônios, os hepatócitos e as células endoteliais vasculares. Entretanto, os dados disponíveis na literatura científica sobre as características das células-tronco adultas derivadas do estroma do tecido adiposo e os procedimentos para sua obtenção e manipulação no laboratório são inconsistentes. É necessário o desenvolvimento de metodologias e procedimentos eficazes de isolamento dessas células para obtenção de células em quantidade e qualidade suficientes para aplicação terapêutica. Nesta revisão, são discutidos os métodos correntes de coleta de tecido adiposo, isolamento e caracterização de células-tronco adultas derivadas do estroma do tecido adiposo, com ênfase na futura aplicação em medicina regenerativa e nos possíveis desafios nesse recente campo da ciência.Universidade Federal do Vale do São FranciscoUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de PatologiaUniversidade Federal de São Paulo (UNIFESP) Departamento de Neurologia e NeurocirurgiaUNIFESP, EPM, Depto. de PatologiaUNIFESP, Depto. de Neurologia e NeurocirurgiaSciEL

Frequency and body-site distribuition of melanocytic nevi acquired in children and teenagers with of the 2 to 18 years old, from public nurseries and school in the city of Votuporanga, State of São Paulo, Brazil

Objetivo: Avaliar, por meio de estudo epidemiologico, a frequencia e a distribuicao corporea dos nevos melanociticos adquiridos (NMA) e observar a influencia das variaveis ambientais e constitucionais nos fenotipos heterogeneos, em uma regiao geografica de intensa exposicao solar. Metodos: Foi realizado estudo transversal das frequencias absoluta e relativa dos NMA de todos os tamanhos, com a inclusao de todas as regioes anatomicas padronizadas pelo protocolo internacional (IARCI OMS, 1990), em 1.279 criancas e adolescentes, com idades de 2 a 18 anos, de creches e escolas publicas na cidade de Votuporanga (20°S), São Paulo, Brasil. Resultados: Setenta e cinco por cento dos individuos apresentaram ate 13 nevos, 50 por cento ate seis nevos e 5 por cento mais de 30 nevos. A contagem de NMA de todos os tamanhos foi mais alta nas regioes toracica e abdominal superior, ombros, face e dorso. Os membros superiores apresentaram mais NMA do que os membros inferiores e houve baixa contagem de NMA nas maos e nos pes. O sexo feminino apresentou quantidade de NMA estatisticamente semelhante ao sexo masculino. As mulheres apresentaram maior contagem de NMA nas faces externas dos membros superiores, face interna do membro superior direito, faces anteriores e posteriores dos membros inferiores, e gluteos. Os homens apresentaram maior contagem de NMA na regiao posterior do pescoco. Observou-se aumento progressivo da contagem de NMA com a idade, com picos aos 13 e aos 16 anos. As regioes de exposicao solar apresentaram maior numero de NMA de maiores diametros (ombros, torax, abdome superior, face e dorso). Os tamanhos dos NMA apresentaram correlacao com a idade, exceto para os gluteos, faces internas dos membros superiores e face posterior da perna direita. Houve forte correlacao entre o numero de NMA e o complexo de pele tipo 3. Exposicao solar, cor dos cabelos e dos olhos, efelides e queimadura solar, tambem apresentaram associacao com alta contagem dos NMA. Conclusoes: Os NMA estao distribuidos por toda a superficie corporal, e em maior numero e tamanho nas regioes de exposicao solar. O aparecimento precoce dos NMA, a distribuicao corporea e a contagem baixa de NMA na populacao heterogenea sustentam a hipotese de que a miscigenacao racial e as regioes anatomicas especificas apresentam diferencas no potencial de proliferacao dos nevosBV UNIFESP: Teses e dissertaçõe

Hyperandrogenism and skin: polycystic ovary syndrome and peripheral insulin resistance

The polycystic ovary syndrome is an extremely common endocrine disorder in women of chilbearing age. It is characterized by menstrual disturbance, hyperandrogenism and/or hyperandrogenemia. The primary pathophysiological defect is unknown, but important characteristics include insulin resistance, androgen excess and impaired gonadotropin dynamics. The most frequent clinical characteristics of polycystic ovary syndrome are associated with the pilosebaceous unit, such as hirsutism, acne, seborrhea and alopecia. Thus, the dermatologist may be responsible for making an early diagnosis of the syndrome, thus preventing delay in establishing preventive and therapeutic measures. The current management recommended for skin manifestations of polycystic ovary syndrome includes combined oral contraceptives, antiandrogens and insulin-sensitizing agents, besides changes in life style. This is a review article on diagnosis, pathophysiology and treatment of polycystic ovary syndrome. The authors emphasize that a clear understanding of pathophysiology of this syndrome, especially by dermatologists, is crucial for its preventive treatment through the different phases in the life of women.A síndrome do ovário policístico é distúrbio endócrino feminino, extremamente comum na idade reprodutiva. Caracteriza-se por anormalidades menstruais, hiperandrogenismo e/ou hiperandrogenemia. A principal alteração na fisiopatologia é desconhecida. Entretanto, parece que a resistência à insulina, o hiperandrogenismo e a alteração na dinâmica das gonadotropinas são os mais importantes mecanismos fisiopatológicos envolvidos. As características clínicas mais freqüentes da síndrome do ovário policístico estão relacionadas com a unidade pilossebácea, como hirsutismo, acne, seborréia e alopecia. Desse modo, o dermatologista pode ser responsável pelo diagnóstico precoce da síndrome, evitando o retardo na instituição de medidas terapêutico-preventivas. Atualmente, as drogas recomendadas para as manifestações cutâneas da síndrome do ovário policístico são os contraceptivos orais conjugados, antiandrógenos e sensibilizantes de insulina e, além disso, é geralmente recomendada a modificação no estilo de vida. Trata-se de artigo de revisão sobre diagnóstico, fisiopatologia e tratamento da síndrome do ovário policístico. Os autores enfatizam que o conhecimento da fisiopatologia dessa síndrome, principalmente pelos dermatologistas, é fundamental para seu tratamento preventivo, nas diferentes fases da vida da mulher.Universidade Federal de São Paulo (UNIFESP) Departamento de DermatologiaUNIFESP, Depto. de DermatologiaSciEL

“Courageous but insolent”: African soldiers in the Dutch East Indies as seen by Dutch officials and Indonesian neighbours

Labour shortages were endemic in colonial societies. Plantation and mining labour was notoriously unattractive, but the army posed problems of its own. In their search to satisfy the voracious appetite for labour in commercial empires and colonial societies, rulers developed racial and ethnic stereotypes as to which “race” was most suitable to perform certain jobs. Africans were deemed most suitable for hard physical labour in tropical climates. They were also portrayed as “martial races”, fit to fill the manpower needs of both Islamic and European armies. This article will first give a brief overview of the use of African labour in the Dutch East Indies. Next, I discuss in more detail one peculiar aspect of inter colonial labour migration in the Dutch colonial empire: the recruitment of West African soldiers for the Dutch East Indies army in the 19th century

Synergistic effect of bioactive lipid and condition medium on cardiac differentiation of human mesenchymal stem cells from different tissues

Human umbilical cord mesenchymal stem cells (hUCMSCs) and human adipose tissue mesenchymal stem cells (hATMSCs) have the potential to differentiate into cardiomyocytes, making them promising therapeutic candidates for treating damaged cardiac tissues. Currently, however, the differentiated cells induced from hUCMSCs or hATMSCs can hardly display functional characteristics similar to cardiomyocytes. In this study, we have investigated the effects of bioactive lipid sphingosine‐1‐phosphate (S1P) on cardiac differentiations of hUCMSCs and hATMSCs in condition medium composed of cardiac myocytes culture medium or 5‐azacytidine. Cardiac differentiations were identified through immunofluorescence staining, and the results were observed with fluorescence microscopy and confocal microscopy. Synergistic effects of S1P and condition medium on cell viability were evaluated by MTT assays. Functional characteristics similar to cardiomyocytes were evaluated through detecting calcium transient. The differentiated hUCMSCs or hATMSCs in each group into cardiomyocytes showed positive expressions of cardiac specific proteins, including α‐actin, connexin‐43 and myosin heavy chain‐6 (MYH‐6). MTT assays showed that suitable differentiation time was 14 days and that the optimal concentration of S1P was 0.5 μM. Moreover, incorporation of S1P and cardiac myocytes culture medium gave rise to calcium transients, an important marker for displaying in vivo electrophysiological properties. This feature was not observed in the S1P‐5‐azacytidine group, indicating the possible lack of cellular stimuli such as transforming growth factor‐beta, TGF‐β

Reconstruction of Endometrium from Human Endometrial Side Population Cell Lines

Endometrial regeneration is mediated, at least in part, by the existence of a specialized somatic stem cell (SSC) population recently identified by several groups using the side population (SP) technique. We previously demonstrated that endometrial SP displays genotypic, phenotypic and the functional capability to develop human endometrium after subcutaneous injection in NOD-SCID mice. We have now established seven human endometrial SP (hESP) cell lines (ICE 1–7): four from the epithelial and three from the stromal fraction, respectively. SP cell lines were generated under hypoxic conditions based on their cloning efficiency ability, cultured for 12–15 passages (20 weeks) and cryopreserved. Cell lines displayed normal 46XX karyotype, intermediate telomerase activity pattern and expressed mRNAs encoding proteins that are considered characteristic of undifferentiated cells (Oct-4, GDF3, DNMT3B, Nanog, GABR3) and those of mesodermal origin (WT1, Cardiac Actin, Enolase, Globin, REN). Phenotype analysis corroborated their epithelial (CD9+) or stromal (vimentin+) cell origin and mesenchymal (CD90+, CD73+ and CD45−) attributes. Markers considered characteristic of ectoderm or endoderm were not detected. Cells did not express either estrogen receptor alpha (ERα) or progesterone receptor (PR). The hESP cell lines were able to differentiate in vitro into adipocytes and osteocytes, which confirmed their mesenchymal origin. Finally, we demonstrated their ability to generate human endometrium when transplanted beneath the renal capsule of NOD-SCID mice. These findings confirm that SP cells exhibit key features of human endometrial SSC and open up new possibilities for the understanding of gynecological disorders such as endometriosis or Asherman syndrome. Our cell lines can be a valuable model to investigate new targets for endometrium proliferation in endometriosis