Cytotoxicity of Calcium Hydroxide on Human Umbilical Cord Mesenchymal Stem Cells

Abstract Objective: To examine the cytotoxicity of calcium hydroxide on human umbilical cord mesenchymal stem cells (HUCMSC) to understand the characteristics for use in regenerative dentistry procedures especially regenerative endodontics. Material and Methods: HUCMSC was isolated, cultured, and confirmed by flow cytometry. The biological characteristics, such as cell morphology, proliferation, and protein expression, were screened. To check the cytotoxicity, HUCMSC was cultured and divided into two groups, the control group (cultured in minimum essential medium (MEM) alpha) and calcium hydroxide group (cultured in MEM alpha and calcium hydroxide). Methyl-thiazole-tetrazolium (MTT) assay was done on different concentrations of calcium hydroxide (0.39 to 25 µg/mL) and the cells were observed and counted. One-way ANOVA test was used with a significance level set at 5%. Results: Flow cytometric analysis confirmed positive of CD73, CD90, CD105, negative of CD45 and CD34. A significant difference was found between the concentration of 6.25 and 3.125 µg/mL (p=0.004). There was no significant difference among 6.25, 12.5 and 25 µg/mL concentrations. There was also no significant difference among 0.39, 0.78, 1.56, and 3.125 µg/mL concentrations. Conclusion: Even though calcium hydroxide is a medicament of choice in clinical endodontics, it decreases the viability of HUCMSC. The lower the concentration of calcium hydroxide, the higher the viability of HUCMSC.

Isolation of Secretome with Enhanced Antifibrotic Properties from miR-214-Transfected Adipose-Derived Stem Cells

BACKGROUND: Secretome refers to the total set of molecules secreted or surface-shed by stem cells. The limitations of stem cell research have led numerous investigators to turn their attention to the use of secretome instead of stem cells. In this study, we intended to reinforce antifibrotic properties of the secretome released from adipose-derived stem cells (ASCs) transfected with miR-214. METHODS: We generated miR-214-transfected ASCs, and extracted the secretome (miR214-secretome) from conditioned media of the transfected ASCs through a series of ultrafiltrations. Subsequently, we intravenously injected the miR-214-secretome into mice with liver fibrosis, and determined the effects of miR-214-secretome on liver fibrosis. RESULTS: Compared with that by naïve secretome, liver fibrosis was ameliorated by intravenous infusion of miR-214-secretome into mice with liver fibrosis, which was demonstrated by significantly lower expression of fibrosis-related markers (alpha-smooth muscle actin, transforming growth factor-β, and metalloproteinases-2) in the livers as well as lower fibrotic scores in the special stained livers compared with naïve secretome. The infusion of miR-214-secretome also led to lesser local and systemic inflammation, higher expression of an antioxidant enzyme (superoxide dismutase), and higher liver proliferative and synthetic function. CONCLUSION: MicroRNA-214 transfection stimulates ASCs to release the secretome with higher antifibrotic and anti-inflammatory properties. miR-214-secretome is thus expected to be one of the prominent ways of overcoming liver fibrosis, if further studies consistently validate its safety and efficiency.

PD-L1 Expression on Circulating CD34+ Hematopoietic Stem Cells Closely Correlated with T-cell Apoptosis in Chronic Hepatitis C Infected Patients

BACKGROUND AND OBJECTIVES: Lack of understanding of the interplay between hematopoietic stem cells (HSCs) and the immune system has severely hampered stem cell research. Programmed death-1 (PD-L1) has been reported on parenchymal cells in patients with chronically inflamed livers and found to play an essential role in T cell homeostasis regulation. However, the bidirectional interaction between HSCs and lymphocytes remains elusive. Here, we aimed to get more insight into circulating CD34+ HSCs PD-L1 expression and T cell apoptosis in chronic HCV infected patients. METHODS: CD34+ HSCs were isolated and purified by immunomagnetic separation. PD-L1 expression was analyzed by quantitative PCR and flow cytometry. Furthermore, co-culture experiments between CD34+ HSCs and T-lymphocytes were established. T-cell lymphocyte apoptosis in peripheral blood and in cultures was detected. RESULTS: CD34+ HSCs constitutively express low levels of PD-L1. Its expression is up-regulated in chronic HCV infected patients. Moreover, PD-L1 expression on circulating CD34+ HSCs enhanced T cell apoptosis in peripheral blood and co-culture. CONCLUSION: Our results suggest novel bidirectional interplay between HSCs and lymphocytes mediated by PD-L1 expression on CD34+ HSCs. PD-L1 expression correlated with T-cell lymphocyte apoptosis. This may contribute to immunomodulatory properties of HSCs which improves its use for allogeneic transplantation.

Pesquisa com células-tronco no Brasil: a produção de um novo campo científico / Stem cell research in Brazil: the production of a new field of science

Resumo O artigo apresenta um panorama das pesquisas com células-tronco no Brasil, a partir de levantamento bibliográfico de artigos de pesquisadores brasileiros, publicados no início do século XXI. A análise das produções evidenciou três eixos centrais na abordagem da temática: o âmbito de fomentos destinados a investigações brasileiras com células-tronco; os estudos pré-clínicos e clínicos realizados no país; e análises socioantropológicas com foco em questões éticas e legais. O artigo aponta aspectos controversos na construção desse campo científico, especialmente vinculados à mídia, como propagadora de valores e determinadas representações sociais, com destaque para novas modalidades de esperança. Nesse cenário de incertezas, encontram-se enfermos e familiares, mobilizados pelas promessas da “medicina do futuro”.

Abstract Based on a review of the literature published in the early twenty-first century by Brazilian researchers, the article offers an overview of stem cell research in Brazil. Three central topics were detected in these papers: (1) the funding of stem cell research in Brazil; (2) preclinical and clinical trials in Brazil; and (3) social anthropological analysis focused on ethical and legal matters. Our review identifies controversial questions in the construction of this scientific field, especially issues involving the media as a disseminator of values and of certain social representations, where new kinds of hope figure large. Within this climate of uncertainty, we find patients and their families energized by the promises of the “medicine of the future.”

Recent Advances in Stem Cell Researches and Their Future Perspectives in Regenerative Medicine

No abstract available.

Adult Stem Cells of Orofacial Origin: Current Knowledge and Limitation and Future Trend in Regenerative Medicine

Stem cell research is one of the most rapidly expanding field of medicine which provides significant opportunities for therapeutic and regenerative applications. Different types of stem cells have been isolated investigating their accessibility, control of the differentiation pathway and additional immunomodulatory properties. Bulk of the literature focus has been on the study and potential applications of adult stem cells (ASC) because of their low immunogenicity and reduced ethical considerations. This review paper summarizes the basic available literature on different types of ASC with special focus on stem cells from dental and orofacial origin. ASC have been isolated from different sources, however, isolation of ASC from orofacial tissues has provided a novel promising alternative. These cells offer a great potential in the future of therapeutic and regenerative medicine because of their remarkable availability at low cost while allowing minimally invasive isolation procedures. Furthermore, their immunomodulatory and anti-inflammatory potential is of particular interest. However, there are conflicting reports in the literature regarding their particular biology and full clinical potentials. Sound knowledge and higher control over proliferation and differentiation mechanisms are prerequisites for clinical applications of these cells. Therefore, further standardized basic and translational studies are required to increase the reproducibility and reduce the controversies of studies, which in turn facilitate comparison of related literature and enhance further development in the field.

Three-dimensional printing for craniomaxillofacial regeneration

Craniomaxillofacial injuries produce complex wound environments involving various tissue types and treatment strategies. In a clinical setting, care is taken to properly irrigate and stabilize the injury, while grafts are molded in an attempt to maintain physiological functionality and cosmesis. This often requires multiple surgeries and grafts leading to added discomfort, pain and financial burden. Many of these injuries can lead to disfigurement and resultant loss of system function including mastication, respiration, and articulation, and these can lead to acute and long-term psychological impact on the patient. A main causality of these issues is the lack of an ability to spatially control pre-injury morphology while maintaining shape and function. With the advent of additive manufacturing (three-dimensional printing) and its use in conjunction with biomaterial regenerative strategies and stem cell research, there is an increased potential capacity to alleviate such limitations. This review focuses on the current capabilities of additive manufacturing platforms, completed research and potential for future uses in the treatment of craniomaxillofacial injuries, with an in-depth discussion of regeneration of the periodontal complex and teeth.

Three-dimensional printing for craniomaxillofacial regeneration

Craniomaxillofacial injuries produce complex wound environments involving various tissue types and treatment strategies. In a clinical setting, care is taken to properly irrigate and stabilize the injury, while grafts are molded in an attempt to maintain physiological functionality and cosmesis. This often requires multiple surgeries and grafts leading to added discomfort, pain and financial burden. Many of these injuries can lead to disfigurement and resultant loss of system function including mastication, respiration, and articulation, and these can lead to acute and long-term psychological impact on the patient. A main causality of these issues is the lack of an ability to spatially control pre-injury morphology while maintaining shape and function. With the advent of additive manufacturing (three-dimensional printing) and its use in conjunction with biomaterial regenerative strategies and stem cell research, there is an increased potential capacity to alleviate such limitations. This review focuses on the current capabilities of additive manufacturing platforms, completed research and potential for future uses in the treatment of craniomaxillofacial injuries, with an in-depth discussion of regeneration of the periodontal complex and teeth.

Participação do nicho endosteal na regulação da hemopoese de camundongos submetidos à desnutrição proteica / Endosteal niche participation in the hematopoiesis of mice submitted to protein malnourishment

O nicho endosteal da medula óssea abriga as células-tronco hemopoéticas (CTH) em quiescência/autorrenovação. As CTH podem ser classificadas em dois grupos: células que reconstituem a hemopoese em longo prazo (LT-CTH) e curto prazo (CT-CTH). Investigamos, neste trabalho, os efeitos da desnutrição proteica (DP) no tecido ósseo e a participação do nicho endosteal na sinalização osteoblasto-CTH. Para tanto, utilizamos camundongos submetidos à DP induzida pelo consumo de ração hipoproteica. Os animais desnutridos apresentaram pancitopenia e diminuição nas concentrações de proteínas séricas e albumina. Quantificamos as CTH por citometria de fluxo e verificamos que os desnutridos apresentaram menor porcentagem de LT-CTH, CT-CTH e de progenitores multipotentes (PMP). Avaliamos a expressão das proteínas CD44, CXCR4, Tie-2 e Notch-1 nas LT-CTH. Observamos diminuição da expressão da proteína CD44 nos desnutridos. Isolamos as células LT-CTH por cell sorting e avaliamos a expressão gênica de CD44, CXCR4 e NOTCH-1. Verificamos que os desnutridos apresentaram menor expressão de CD44. Em relação ao ciclo celular, verificamos maior quantidade de LT-CTH nas fases G0/G1. Caracterizamos as alterações do tecido ósseo femoral, in vivo. Observamos diminuição da densidade mineral óssea e da densidade medular nos desnutridos. A desnutrição acarretou diminuição da área média das seções transversais, do perímetro do periósteo e do endósteo na cortical do fêmur dos animais. E na região trabecular, verificou-se diminuição da razão entre volume ósseo e volume da amostra e do número de trabéculas, aumento da distância entre as trabéculas e prevalência de trabéculas ósseas em formato cilíndrico. Avaliamos a expressão de colágeno, osteonectina (ON) e osteocalcina (OC) por imuno-histoquímica, e de osteopontina (OPN) por imunofluorescência no fêmur e verificamos diminuição da marcação para OPN, colágeno tipo I, OC e ON nos desnutridos. Evidenciamos, pela técnica do Picrosírius, desorganização na distribuição das fibras colágenas e presença de fibras tipo III nos fêmures dos desnutridos, além de maior número de osteoclastos evidenciados pela reação da fosfatase ácida tartarato resistente. Os osteoblastos da região femoral foram isolados por depleção imunomagnética, imunofenotipados por citometria de fluxo e cultivados em meio de indução osteogênica. Observamos menor positividade para fosfatase alcalina e vermelho de alizarina nas culturas dos osteoblastos dos desnutridos. Avaliamos, por Western Blotting, a expressão de colágeno tipo I, OPN, osterix, Runx2, RANKL e osteoprotegerina (OPG), e, por PCR em tempo real, a expressão de COL1A2, SP7, CXCL12, ANGPT1, SPP1, JAG2 e CDH2 nos osteoblastos isolados. Verificamos que a desnutrição acarretou diminuição da expressão proteica de osterix e OPG e menor expressão gênica de ANGPT1. Avaliamos a proliferação das células LSK (Lin-Sca1+c-Kit+) utilizando ensaio de CFSE (carboxifluoresceína succinimidil ester). Foi realizada cocultura de células LSK e osteoblastos (MC3T3-E1) na presença e ausência de anti-CD44. Após uma semana, verificamos menor proliferação das LSK dos desnutridos. O bloqueio de CD44 das LSK do grupo controle diminuiu a proliferação destas em três gerações. Entretanto, nos desnutridos, esse bloqueio não afetou a proliferação. Concluímos que a DP promoveu alterações no tecido ósseo e nas CTH. Entretanto, não podemos afirmar que as alterações observadas no sistema hemopoético foram decorrentes de alterações exclusivas do nicho endosteal

The bone marrow endosteal niche hosts hematopoietic stem cells (HSC) in quiescence/self-renewal. HSC can be classified into two groups: cells capable of renewing indefinitely (LT-HSC) or repopulating in the short term (ST-HSC). In this work, we investigated the effects of protein malnutrition (PM) on bone tissue and the involvement of the endosteal niche in osteoblast-CTH signaling. Therefore, we used mice subjected to PM induced by the consumption of hypoproteic feed. Malnourished animals presented pancytopenia and decreased concentration of serum protein and albumin. We quantified the HSC by flow cytometry and found that the malnourished ones had lower percentage of LT-HSC, ST-HSC and multipotent progenitors (MPP). We assessed the expression of the CD44, CXCR4, Tie-2 and Notch-1 proteins in LT-HSC. We observed decreased expression of CD44 protein with the malnourished ones. We isolated the LT-HSC cells by means of cell sorting and assessed the gene expression of CD44, CXCR4 and NOTCH-1. We found that malnutrition had lower expression of CD44. Regarding the cell cycle, we see greater amount of LT-HSC in the G0 and G1 phases. We characterized the changes of the femoral bone tissue in vivo. We observed a decrease in the bone mineral density and medullar density in malnourished animals. As for malnourished animals, the femoral cortical region showed a significant decrease in tissue area, periosteal and endosteal perimeter. The femoral trabecular region of malnourished animals showed decreased bone volume/tissue volume ratio, decreased trabecular number, increased trabecular separation and prevalence of rod-like trabeculae. We investigated the expression of collagen, osteonectin (ON) and osteocalcin (OC) by means of immunohistochemistry and the expression of osteopontin (OPN) by immunofluorescence and we found that malnourished animals showed decreased labeling for OPN, type I collagen, OC and ON in the cortical region of the femur. Picrosirius staining was used to analyze disorganization of collagen fibers and presence of type III fibers in the femurs of the malnourished. Cortical and trabecular regions of malnourished animals presented a higher number of osteoclasts as shown by tartrate-resistant acid phosphatase reaction. Moreover, osteoblasts were isolated from the femoral region by immunomagnetic depletion and immunophenotyped by flow cytometry and cultured in osteogenic induction medium. Results proved less positive for alkaline phosphatase and alizarin red in the cultures of osteoblasts of malnourished animals. We assessed, by means of Western blotting, type I collagen expression, OPN, osterix, Runx2, RANKL and osteoprotegerin (OPG) and, by real time PCR, the expression of COL1A2, SP7, CXCL12, ANGPT1, SPP1, JAG2 and CDH2 with the isolated osteoblasts. We found that malnutrition led to osterix and OPG decreased protein expression and lower ANGPT1 gene expression. We evaluated LSK cell (Lin-Sca1+c-Kit+) proliferation by CFSE (carboxyfluorescein succinimidyl ester). LSK cells and osteoblasts (MC3T3-E1) cocultures were performed in the presence and absence of anti-CD44. After a week, we found lower proliferation of LSK in the malnourished. The LSK CD44 blocking in the control group decreased the proliferation of these three generations. However, as for the malnourished, such blockage did not affect proliferation. We concluded that the PM has promoted changes in bone tissue and the CTH. However, we can't claim that the alterations observed in hematopoietic system were due to endosteal niche-only changes

New technologies in biomedicine. Opinions of young Romanian physicians / Nuevas tecnologías en biomedicina. Opiniones de médicos jóvenes de Rumania / Novas tecnologias em biomedicina. Opiniões de jovens médicos romenos

Aim. The purpose of this article is to summarize the way young medical professionals view these modern biomedical procedures and their moral acceptability. Materials and methods. A survey, filled in online, analyzing items in four main areas: genetic techniques, cloning, stem cell research, and assisted reproduction. Results. Genetics related items. Most subjects agreed that the right to the genetic material should be a fundamental human right and that genetic engineering should be used if it could lead to the elimination os severe genetic diseases like cystic fibrosis and thalassemia. The least acceptance rate was obtained for techniques that would either change physical traits (like eye or hair color) or augment them. Assisted reproductive techniques. Most subjects agreed that the prenatal screening should be mandatory, and if the screening detects a severe congenital malformation the physician should recommend therapeutic abortion. Cloning. Most subjects disagreed that cloning of any type, either therapeutic or reproductive, using human, animal, or vegetal genetic material. Stem cell research. Most subjects agreed with the collection and storage of cord blood stem cells and the use of adult stem cells, and most of them disagreed with the creation of embryos specifically for obtaining stem cells. Conclusions. Even if the national legislation in this area is very scarce, the responses have usually identified the highly controversial techniques. If however the national legislation has elements similar to the items from the survey, they tended to take the respective items as morally acceptable without trying to analyze them critically.

Objetivo. El propósito de este artículo es recoger la forma en que jóvenes profesionales médicos ven los procedimientos biomédicos modernos y su aceptabilidad moral. Materiales y métodos: Una encuesta, rellenada online, que analiza elementos en cuatro áreas principales: técnicas genéticas, clonación, investigación con células madre y reproducción asistida. Resultados: Elementos relacionados con la genética: La mayoría de los sujetos acepta que el derecho a material genético debería ser un derecho humano fundamental y que la ingeniería genética debería usarse si pudiese eliminar enfermedades genéticas severas como la fibrosis quística y la talasemia. Se obtuvo una frecuencia de aceptación menor para técnicas que pudieran o cambiar características físicas (como el color de los ojos o del pelo) o aumentarlas. Técnicas de reproducción asistida: La mayoría de los sujetos acepta que el examen de detección prenatal debiera ser mandatorio y si se detecta una deformación congénita severa, el médico debería recomendar aborto terapéutico. Clonación: La mayoría de los sujetos no acepta clonación de ningún tipo, terapéutica o reproductiva, usando material genético humano, animal o vegetal. Investigación con células madre: La mayoría de los sujetos acepta recoger y almacenar células madre del cordón umbilical y el uso de células madre adultas y está en desacuerdo con la creación de embriones específicamente para obtener células madre. Conclusiones: aunque la legislación nacional en esta área es muy escasa, las respuestas por lo general han identificado las técnicas altamente controversiales. Sin embargo, si la legislación nacional tiene elementos similares a los temas de la encuesta, se tiende a tomarlos respectivamente como moralmente aceptables sin tratar de analizarlos críticamente.

Objetivo. A proposta deste artigo é sumarizar o modo de ver dos jovens profissionais médicos sobre procedimentos biomédicos modernos e sua aceitação moral. Materiais e métodos. Uma pesquisa de opinião realizada online, analisou ítens de quatro principais áreas: técnicas genéticas, clonagem, pesquisa com células-tronco, e reprodução assistida. Resultados. Itens relacionados à Genética. A maioria dos sujeitos concordaram que o direito ao material genético deveria ser um direito humano fundamental e que a engenharia genética poderia ser usada se puder levar à eliminação de doenças genéticas severas como a fibrose cística e a talassemia. A menor taxa de aceitação foi obtida para técnicas que pudessem modificar o aspecto físico individual (como olho e cor do cabelo) ou aumentá-los. Técnicas de reprodução assistida. A maioria dos sujeitos concordaram que a seleção pré-natal (screening) deverá ser impositiva, e que se o "screening" detetar uma severa malformação congênita o médico deveria recomendar o aborto terapêutico. Clonagem. A maioria dos sujeitos discordaram da clonagem de qualquer tipo, terapêutica ou reprodutiva, com material genético de uso humano, animal, ou vegetal. Pesquisa com células-tronco. A maioria dos sujeitos concordaram com a obtenção e estocagem de células-tronco de sangue do cordão umbilical e a utilização de células-tronco adultas , e a maioria deles discordaram da criação de embriões especificamente para a obtenção de células-tronco. Conclusões. Mesmo que a legislação nacional na área seja muito escassa, as respostas usualmente identificaram as técnicas como altamente controversas. Quando a legislação nacional oferece elementos semelhantes aos ítens obtidos pela pesquisa de opinião, eles tenderiam a tomar os respectivos ítens como moralmente aceitáveis sem tentar analisá-los criticamente.

Produção científica brasileira sobre células-tronco de 2000 a 2013:características e colaboração internacional / Brazilian scientific output in stem cells from 2000 till 2013: features and international collaboration / Producción científica brasileña acerca de células madre en los años 2000-2013: características y colaboración internacional

Este artigo analisa a produção científica brasileira sobre células-tronco publicada entre 2000 e 2013 e indexada na Web of Science (WoS). A pesquisa constitui um estudo bibliométrico, e os resultados revelam o crescimento significativo da produção científica, o predomínio dos artigos e a preferência pelo idioma inglês. Entre as instituições mais produtivas destacam-se a Universidade de São Paulo e a Universidade Federal do Rio de Janeiro. As áreas de hematologia e transplante recebem destaque na classificação temática dessa produção científica, marcada pela interdisciplinaridade. O núcleo dos periódicos revela forte presença dos títulos estrangeiros e indica a difusão internacional da produção científica. A colaboração internacional alcançou o índice de 31,3% e reuniu 56 países parceiros, com destaque para EUA, Alemanha e França. Considera-se que o Brasil tem-se estabelecido como um importante agente nas pesquisas sobre células tronco e que a produção científica tende a se expandir nos próximos anos e a alcançar maior visibilidade internacional...

This article analyzes the Brazilian scientific output in stem cells published from 2000 till 2013 andindexed in the Web of Science (WoS). The research constitutes a bibliometric study and the results showthe significant growth of the scientific output, the predominance of articles and the preference for the English language. Among the most productive institutions stand out the Universidade de São Paulo and the Universidade Federal do Rio de Janeiro. The areas hematology and transplantation are highlightedin thematic classification of scientific output marked by the interdisciplinarity. The core of journals reveals strong presence of foreign journals and indicates the international diffusion of scientific output. International collaboration has achieved the index of 31.3% and brought together 56 partner countries, especially USA, Germany and France. It is considered that Brazil has established itself as an important agent in research on stem cells and that scientific output is likely to increase in the coming years and toreach greater international visibility...

Este artículo analiza la producción científica brasileña acerca de células madre publicada entre 2000 y2013 e indexada en la Web of Science (WoS). La investigación constituye un estudio bibliométrico y los resultados muestran el importante crecimiento de la producción científica, el predominio de los artículosy la preferencia por el idioma inglés. Entre las instituciones más productivas están la Universidade de São Paulo y la Universidade Federal do Rio de Janeiro. Las áreas de hematología y trasplante se destacan enla clasificación temática de la producción científica marcada por la interdisciplinariedad. El núcleo de las revistas revela fuerte presencia de títulos extranjeros e indica la difusión internacional de la producción científica. La colaboración internacional ha alcanzado la tasa de 31,3% y reunió 56 países asociados, en especial, Estados Unidos, Alemania y Francia. Se considera que Brasil se ha consolidado como un agente importante en la investigación sobre las células madre y que la producción científica probablemente aumentará en los próximos años y alcanzará una mayor visibilidad internacional...

Células madre e ingeniería de tejidos: los avances y desafíos de la odontología del futuro / Stem cells and tissue engineering: the advances and challenges of the future dentistry

En los días actuales, con los avances de la ingeniería de tejidos, el principal objetivo de los investigadores es desarrollar una tercera dentición, utilizando células madre. Nuestro trabajo tuvo como objetivo un levantamiento bibliográfico acerca de la utilización de células madre en odontología para la regeneración de los tejidos bucales. Para este trabajo, llevamos en consideración la información de artículos nacionales e internacionales de 2006 hasta 2014, construyendo una tabla. Sabemos que las células madre son muy especiales y prometen revolucionar la historia de la odontología mundialmente, solucionando grandes problemas clínicos.

New Horizons in Stem Cell Research / 한양의대학술지

No abstract available.

Advanced Research on Stem Cell Therapy for Hepatic Diseases: Potential Implications of a Placenta-derived Mesenchymal Stem Cell-based Strategy / 한양의대학술지

The category of chronic liver diseases comprise one of the most common medical diagnoses worldwide. Currently, orthotopic liver transplantation is the only effective treatment for end-stage hepatic disease, but this procedure is associated with many problems, including donor scarcity, operative damage, high cost, risk of immune rejection and lifelong immunosuppressive treatments. Thus, the development of new therapies is highly desirable. Cell therapy with stem cells is increasingly being used to repair damaged tissue or to promote organ regeneration. Stem cells, which possess self-renewal activity as well as differentiation potential, can be categorized as embryonic stem cells (ESCs) or adult stem cells (ASCs), which include hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). Recently, placenta-derived mesenchymal stem cells (PD-MSCs) have been reported, and they are attracting much interest in stem cell research for their multiple advantages: 1) no ethical concerns, 2) the ability to obtain abundant cell numbers, 3) multi-lineage differentiation potential, and 4) strong immunosuppressive properties. PD-MSCs differentiate into hepatocyte-like cells when exposed to hepatogenic differentiation-inducing conditions and PD-MSCs transplantation has been shown to enhance hepatic regeneration and/or survival in a rat hepatic failure model by suppressing the progression of fibrosis and apoptosis and activating autophagy. In this review, we will explain the characteristics of several kinds of PD-MSCs and discuss recent studies of the therapeutic potential of PD-MSCs in the repair of liver injury and their utility in regenerative medicine. Although many problems remain to be solved, many studies support the potential for human stem cell therapies, including PD-MSCs, as a promising new technology for the therapeutic regeneration of human liver intractably damaged due to chronic disease and/or toxic and environmental insult.

Stem Cell Research in Pakistan; Past, Present and Future

BACKGROUND AND OBJECTIVES: Stem cells have proved to have great therapeutic potential as stem cell treatment is replacing traditional ways of treatment in different disorders like cancer, aplastic anemia, stroke, heart disorders. The developed and developing countries are investing differently in this area of research so research output and clinical translation of research greatly vary among developed and developing countries. Present study was done to investigate the current status of stem cells research in Pakistan and ways to improve it. RESULTS: Many advanced countries (USA, UK and Canada etc.) are investing heavily in stem cell research and treatment. Different developing countries like Iran, Turkey and India are also following the developed countries and investing a lot in stem cells research. Pakistan is also making efforts in establishing this field to get desired benefits but unfortunately the progress is at very low pace. If Government plays an active role along with private sector, stem cell research in Pakistan can be boosted up. The numbers of publications from Pakistan are very less compared to developed and neighboring countries and Pakistan also has very less number of institutes working in this area of research. CONCLUSIONS: Stem cells research is at its initial stages in Pakistan and there is great need to bring Government, academia and industry together so they could make serious efforts to promote research in this very important field. This will help millions of patients suffering from incurable disorders and will also reduce economic loss.

Cell Sources, Liver Support Systems and Liver Tissue Engineering: Alternatives to Liver Transplantation

The liver is the largest organ in the body; it has a complex architecture, wide range of functions and unique regenerative capacity. The growing incidence of liver diseases worldwide requires increased numbers of liver transplant and leads to an ongoing shortage of donor livers. To meet the huge demand, various alternative approaches are being investigated including, hepatic cell transplantation, artificial devices and bioprinting of the organ itself. Adult hepatocytes are the preferred cell sources, but they have limited availability, are difficult to isolate, propagate poor and undergo rapid functional deterioration in vitro. There have been efforts to overcome these drawbacks; by improving culture condition for hepatocytes, providing adequate extracellular matrix, co-culturing with extra-parenchymal cells and identifying other cell sources. Differentiation of human stem cells to hepatocytes has become a major interest in the field of stem cell research and has progressed greatly. At the same time, use of decellularized organ matrices and 3 D printing are emerging cutting-edge technologies for tissue engineering, opening up new paths for liver regenerative medicine. This review provides a compact summary of the issues, and the locations of liver support systems and tissue engineering, with an emphasis on reproducible and useful sources of hepatocytes including various candidates formed by differentiation from stem cells.

Políticas internacionais em ciência e saúde: a pesquisa celular e a medicina regenerativa / International policies in science and health: cellular research and regenerative medicine

O desenvolvimento de medicamentos e terapias baseados nos princípios científicos das biociências e das biotecnologias da saúde - com base em células vivas e difíceis de serem estandardizadas - tem sido um tema de amplos debates públicos em nível global. A área tem sido recentemente demarcada como medicina regenerativa, que inclui as pesquisas e terapias com células-tronco (PCT e TC), foco deste estudo. No presente artigo, apresentam-se os principais eventos históricos na área de pesquisa celular, descreve-se o estágio atual na evolução da medicina regenerativa e as características das principais políticas desenvolvidas, em especial pelos países de liderança global, e em relação à regulamentação dos direitos de propriedade intelectual. Desenvolve-se análise quantitativa e qualitativa com dados secundários coletados em nível internacional, revisão bibliográfica e de informações em arquivos das instituições de regulamentação globais, resenhas jornalísticas atualizadas, assim como de artigos especializados publicados em revistas internacionais. A revisão da informação é guiada pelas seguintes perguntas: quais são as trajetórias principais de inovação em ciência e saúde nessa área? Quais fatores incidem principalmente na sua evolução? Conclui-se com reflexões específicas sobre os impactos dos desenvolvimentos associados na Saúde Coletiva...

Medicine and therapy developments based upon scientific principles of biosciences and health biotechnologies - with the use of live cells which are difficult to standardize - have been subject of wide public debates at the global level. The area has been recently defined as one of regenerative medicine that includes stem cell research and therapy, the focus of our study. This paper presents the main historical research events in cellular research, describes regenerative medicine's present stage of evolution and the characteristics of the main public policies developed, most especially in the leading countries and in relation to the regulation of intellectual property rights. A quantitative and qualitative analysis is developed, drawing upon different sets of secondary data collected internationally, bibliographic and archival information from global regulatory institutions, updated journal reviews as well as of specialized articles published in international journals. This information is reviewed guided by the following questions: which are the main trajectories in health innovation in this area? Which factors have most highly influenced its evolution? The paper concludes with reflections on the specific impacts of associated developments on collective health...