LMNA -Lipodystrophies are a group of heterogeneous syndromes, with either genetic or acquired origin, characterized by the accumulation of prelamin A, an inmature form of the protein lamin A, one of the major components of the nuclear lamina. Several molecular studies suggest lamin A is involved in adipocyte development, the disruption of which leads to compromised regulation of adipogenesis, adipocyte lipid droplet formation and maintenance, and subsequent secondary dysfunctions in fat metabolism. Moreover, these diseases clinically present with generalized or partial fat atrophy connected with metabolic complications, such as insulin-resistant diabetes and dyslipidemia, in addition to age associated manifestations. There is a real need to increase our understanding regarding these syndromes because of their import in human health and the lack of knowledge of their etiopathology. To gain deeper insights into these metabolic diseases, we have taken advantage of a previously generated “disease in a dish” model of human LMNA -lipodystrophy based on the pathological accumulation of the precursor prelamin A in stem cell derived adipocytes. This experimental model recapitulates phenotypes observed in lipodystrophic patient’s samples and animal models, and it has been critical in elucidating new insights into the molecular mechanisms governing this set of disorders. Recently, we have identified alterations in fundamental processes of lipid homeostasis such as lipolysis, as well as mitochondrial and endoplasmic reticulum functions, similar to what can be observed in some metabolic and aging phenotypes. Additionally, the lipidomic profile of this lipodystrophic experimental model displayed a lipid metabolic signature similar to aging systems, providing new information concerning metabolic pathways affected during the aging process. By clarifying the fundamental mechanisms governing these aging associated diseases, future novel interventions could be developed that will at least delay the appearance of aging phenotypes and thereby increase the healthspan or disease-free time of an individual.
{"title":"An emerging interplay between altered human lipid metabolism, lipodystrophy and aging","authors":"A. Infante, C. I. Rodríguez","doi":"10.14800/SCTI.982","DOIUrl":"https://doi.org/10.14800/SCTI.982","url":null,"abstract":"LMNA -Lipodystrophies are a group of heterogeneous syndromes, with either genetic or acquired origin, characterized by the accumulation of prelamin A, an inmature form of the protein lamin A, one of the major components of the nuclear lamina. Several molecular studies suggest lamin A is involved in adipocyte development, the disruption of which leads to compromised regulation of adipogenesis, adipocyte lipid droplet formation and maintenance, and subsequent secondary dysfunctions in fat metabolism. Moreover, these diseases clinically present with generalized or partial fat atrophy connected with metabolic complications, such as insulin-resistant diabetes and dyslipidemia, in addition to age associated manifestations. There is a real need to increase our understanding regarding these syndromes because of their import in human health and the lack of knowledge of their etiopathology. To gain deeper insights into these metabolic diseases, we have taken advantage of a previously generated “disease in a dish” model of human LMNA -lipodystrophy based on the pathological accumulation of the precursor prelamin A in stem cell derived adipocytes. This experimental model recapitulates phenotypes observed in lipodystrophic patient’s samples and animal models, and it has been critical in elucidating new insights into the molecular mechanisms governing this set of disorders. Recently, we have identified alterations in fundamental processes of lipid homeostasis such as lipolysis, as well as mitochondrial and endoplasmic reticulum functions, similar to what can be observed in some metabolic and aging phenotypes. Additionally, the lipidomic profile of this lipodystrophic experimental model displayed a lipid metabolic signature similar to aging systems, providing new information concerning metabolic pathways affected during the aging process. By clarifying the fundamental mechanisms governing these aging associated diseases, future novel interventions could be developed that will at least delay the appearance of aging phenotypes and thereby increase the healthspan or disease-free time of an individual.","PeriodicalId":90974,"journal":{"name":"Stem cell and translational investigation","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66658678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Adenosine deaminases acting on RNA (ADARs) are enzymes related in RNA editing that converts adenosine residues to inosine specifically in double-stranded RNAs. ADAR regulates mRNA stability and gene expression. ADAR1-Dicer complexes promote microRNA processing and RNA interference (RNAi) gene silencing. ADAR1 is highly expressed in human pluripotent stem cells. Recently, we observed that ADAR1-deficiency in human iPS cells promotes caspase3-mediated apoptotic cell death. On the other hand, ADAR1-deficiency did not alter cell morphology, alkaline phosphatase (AP) staining activities and the expression levels of pluripotent marker genes, indicating that ADAR1 is not required for maintenance of pluripotency. Further, ADAR1 deficient iPS cells did not change proliferation rate. Altogether, we demonstrated that ADAR1 is necessary for existence of human iPS cells.
{"title":"RNA editing enzyme ADAR1 in human iPS cells","authors":"Shota Katayama","doi":"10.14800/SCTI.914","DOIUrl":"https://doi.org/10.14800/SCTI.914","url":null,"abstract":"Adenosine deaminases acting on RNA (ADARs) are enzymes related in RNA editing that converts adenosine residues to inosine specifically in double-stranded RNAs. ADAR regulates mRNA stability and gene expression. ADAR1-Dicer complexes promote microRNA processing and RNA interference (RNAi) gene silencing. ADAR1 is highly expressed in human pluripotent stem cells. Recently, we observed that ADAR1-deficiency in human iPS cells promotes caspase3-mediated apoptotic cell death. On the other hand, ADAR1-deficiency did not alter cell morphology, alkaline phosphatase (AP) staining activities and the expression levels of pluripotent marker genes, indicating that ADAR1 is not required for maintenance of pluripotency. Further, ADAR1 deficient iPS cells did not change proliferation rate. Altogether, we demonstrated that ADAR1 is necessary for existence of human iPS cells.","PeriodicalId":90974,"journal":{"name":"Stem cell and translational investigation","volume":"97 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66658637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Valproic acid (VPA) is a widely used antiepileptic drug to treat epilepsy and psychiatric disorders, but potentially causes idiosyncratic liver injury. Alpers-Huttenlocher syndrome (AHS), a neurometabolic disorder caused by mutations in mitochondrial DNA polymerase gamma (POLG), is associated with an increased risk of developing fatal VPA hepatotoxicity. However, the mechanistic link of this clinical mystery remains unknown. Here, we established an induced pluripotent stem cell （iPSC） toxicity model to explore the mechanism behind the high risk of VPA-induced liver injury in AHS. By this model, we demonstrated that AHS iPSCs-hepatocytes are more sensitive to VPA-induced mitochondrial-dependent apoptosis than controls. Furthermore, Superoxide flashes, spontaneous bursts of superoxide generation, caused by opening of the mitochondrial permeability transition pore (mPTP), occur more frequently in AHS iPSCs-hepatocytes, and the mPTP inhibitor, cyclosporine A, is able to rescue VPA-induced apoptotic sensitivity. In addition, carnitine and N-acetylcysteine, which has been used to treat VPA-induced liver injury, also rescue VPA-induced apoptotic sensitivity.
{"title":"Mechanism of valproic acid-induced hepatotoxicity in alpers syndrome using an induced pluripotent stem cell model","authors":"Jingyi Guo, Zhongfu Ying, Yi Wu, Xingguo Liu","doi":"10.14800/SCTI.838","DOIUrl":"https://doi.org/10.14800/SCTI.838","url":null,"abstract":"Valproic acid (VPA) is a widely used antiepileptic drug to treat epilepsy and psychiatric disorders, but potentially causes idiosyncratic liver injury. Alpers-Huttenlocher syndrome (AHS), a neurometabolic disorder caused by mutations in mitochondrial DNA polymerase gamma (POLG), is associated with an increased risk of developing fatal VPA hepatotoxicity. However, the mechanistic link of this clinical mystery remains unknown. Here, we established an induced pluripotent stem cell （iPSC） toxicity model to explore the mechanism behind the high risk of VPA-induced liver injury in AHS. By this model, we demonstrated that AHS iPSCs-hepatocytes are more sensitive to VPA-induced mitochondrial-dependent apoptosis than controls. Furthermore, Superoxide flashes, spontaneous bursts of superoxide generation, caused by opening of the mitochondrial permeability transition pore (mPTP), occur more frequently in AHS iPSCs-hepatocytes, and the mPTP inhibitor, cyclosporine A, is able to rescue VPA-induced apoptotic sensitivity. In addition, carnitine and N-acetylcysteine, which has been used to treat VPA-induced liver injury, also rescue VPA-induced apoptotic sensitivity.","PeriodicalId":90974,"journal":{"name":"Stem cell and translational investigation","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66658589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jes G. Kuruvilla, A. Ghaleb, A. Bialkowska, Mandayam Nandan, V. Yang
The intestinal epithelium is a tissue that undergoes continuous self-renewal initiated at the bottom of the crypts, which harbor the intestinal stem cell (ISC) pool. The ISC pool is sub-divided into crypt base columnar (CBC) cells at the crypt bottom and label retention cells (LRC) at position +4 from the crypt bottom. CBC cells are marked by Leucine-rich repeat-containing G-protein coupled receptor (Lgr5) while LRC cells are identified by several markers including Bmi1, mTert, Hopx, Lrig1, and Sox9. Krüppel-like factors (KLFs) belong to a family of transcription factors that exert important physiological function in various tissues. In the intestine, KLF4 is predominantly expressed in the terminally differentiated, non-proliferating cells lining the villus. Its deletion in the adult mouse intestine results in perturbed homeostasis. In contrast, KLF5 is expressed in actively proliferating cells of the intestinal crypt, including CBC cells and transit amplifying (TA) cells. We recently investigated the effect of Klf5 deletion specifically from the Lgr5-expressing CBC cells in adult mouse intestine using an inducible Cre recombinase system. Shortly (3-5 days) after Cre induction, proliferation of both CBC and TA cells ceased, which was accompanied by an increase in apoptosis in the crypt. Beginning at two weeks following Cre induction, both Klf5 expression and proliferation re-appeared but without the re-emergence of Lgr5-positive CBC cells, which were eventually depleted by four months following induction. These findings indicate that KLF5 plays an important role in regulating proliferation and survival of CBC stem cells in the intestine.
{"title":"Role of Krüppel-like factor 5 in the maintenance of the stem cell niche in the intestinal crypt.","authors":"Jes G. Kuruvilla, A. Ghaleb, A. Bialkowska, Mandayam Nandan, V. Yang","doi":"10.14800/SCTI.839","DOIUrl":"https://doi.org/10.14800/SCTI.839","url":null,"abstract":"The intestinal epithelium is a tissue that undergoes continuous self-renewal initiated at the bottom of the crypts, which harbor the intestinal stem cell (ISC) pool. The ISC pool is sub-divided into crypt base columnar (CBC) cells at the crypt bottom and label retention cells (LRC) at position +4 from the crypt bottom. CBC cells are marked by Leucine-rich repeat-containing G-protein coupled receptor (Lgr5) while LRC cells are identified by several markers including Bmi1, mTert, Hopx, Lrig1, and Sox9. Krüppel-like factors (KLFs) belong to a family of transcription factors that exert important physiological function in various tissues. In the intestine, KLF4 is predominantly expressed in the terminally differentiated, non-proliferating cells lining the villus. Its deletion in the adult mouse intestine results in perturbed homeostasis. In contrast, KLF5 is expressed in actively proliferating cells of the intestinal crypt, including CBC cells and transit amplifying (TA) cells. We recently investigated the effect of Klf5 deletion specifically from the Lgr5-expressing CBC cells in adult mouse intestine using an inducible Cre recombinase system. Shortly (3-5 days) after Cre induction, proliferation of both CBC and TA cells ceased, which was accompanied by an increase in apoptosis in the crypt. Beginning at two weeks following Cre induction, both Klf5 expression and proliferation re-appeared but without the re-emergence of Lgr5-positive CBC cells, which were eventually depleted by four months following induction. These findings indicate that KLF5 plays an important role in regulating proliferation and survival of CBC stem cells in the intestine.","PeriodicalId":90974,"journal":{"name":"Stem cell and translational investigation","volume":"100 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66658627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
During the last 2 decades, stem cell therapies with bone marrow mononuclear cells (BMMNCs) or mesenchymal stem cells (MSCs) to treat ischemic heart disease, including in pre-clinical and clinical trials, have demonstrated the ability of stem cells to improve cardiac function, infarct size, and cardiac remodeling in adult patients. In recent years, endogenous cardiac stem cells (CSCs) derived from heart tissue have been identified. CSCs have been shown to have superior regenerative potential over other types of stem cells in terms of cardiovascular-lineage differentiation, paracrine factor secretion, and functional improvement after cell transplantation. Cardiac stem cell therapy to regenerate damaged myocardium after chronic infarction has been reported in the SCIPIO and CADUCEUS trials. In contrast, although recent advances in pediatric cardiology, congenital cardiac surgery, and intensive care management have dramatically changed clinical outcomes, there is an increasing recognition of limited therapeutic improvement in children with severe heart failure. Congenital heart failure is a structural heart disease caused by multiple etiologies related to pressure and volume overload, arrhythmia, and myocardial degradation. Stem cell-based strategies to treat heart failure in adults have been investigated; however, little is known about their safety and efficacy in children and planned clinical studies are quite limited. Only case reports have been published and no large clinical trials have been conducted using any type of stem cells. Recently, the TICAP trial has revealed the safety and feasibility of intracoronary infusion of autologous cardiosphere-derived cells (CDCs) in children with hypoplastic left heart syndrome (HLHS). Although this trial had several limitations that required further evaluation, the results from this study provided a foothold for stem cell-based therapeutic strategies in patients with congenital heart disease. Eventually, a new paradigm of stem cell therapy to treat congenital heart failure has started to form. Many important issues including long-term cell engraftment, the mechanism of stem cell recruitment and differentiation, administration route, and appropriate cell types to deliver in situ remain to be investigated. Here, we review the latest research on stem cell therapies for heart failure and discuss the future perspectives on cell-based regenerative strategies to treat patients with congenital heart diseases.
{"title":"Cardiac stem cell therapies for congenital heart diseases","authors":"S. Ishigami, S. Sano, H. Oh","doi":"10.14800/SCTI.800","DOIUrl":"https://doi.org/10.14800/SCTI.800","url":null,"abstract":"During the last 2 decades, stem cell therapies with bone marrow mononuclear cells (BMMNCs) or mesenchymal stem cells (MSCs) to treat ischemic heart disease, including in pre-clinical and clinical trials, have demonstrated the ability of stem cells to improve cardiac function, infarct size, and cardiac remodeling in adult patients. In recent years, endogenous cardiac stem cells (CSCs) derived from heart tissue have been identified. CSCs have been shown to have superior regenerative potential over other types of stem cells in terms of cardiovascular-lineage differentiation, paracrine factor secretion, and functional improvement after cell transplantation. Cardiac stem cell therapy to regenerate damaged myocardium after chronic infarction has been reported in the SCIPIO and CADUCEUS trials. In contrast, although recent advances in pediatric cardiology, congenital cardiac surgery, and intensive care management have dramatically changed clinical outcomes, there is an increasing recognition of limited therapeutic improvement in children with severe heart failure. Congenital heart failure is a structural heart disease caused by multiple etiologies related to pressure and volume overload, arrhythmia, and myocardial degradation. Stem cell-based strategies to treat heart failure in adults have been investigated; however, little is known about their safety and efficacy in children and planned clinical studies are quite limited. Only case reports have been published and no large clinical trials have been conducted using any type of stem cells. Recently, the TICAP trial has revealed the safety and feasibility of intracoronary infusion of autologous cardiosphere-derived cells (CDCs) in children with hypoplastic left heart syndrome (HLHS). Although this trial had several limitations that required further evaluation, the results from this study provided a foothold for stem cell-based therapeutic strategies in patients with congenital heart disease. Eventually, a new paradigm of stem cell therapy to treat congenital heart failure has started to form. Many important issues including long-term cell engraftment, the mechanism of stem cell recruitment and differentiation, administration route, and appropriate cell types to deliver in situ remain to be investigated. Here, we review the latest research on stem cell therapies for heart failure and discuss the future perspectives on cell-based regenerative strategies to treat patients with congenital heart diseases.","PeriodicalId":90974,"journal":{"name":"Stem cell and translational investigation","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66658577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Adipose-derived stromal/stem cells are easily harvested in large quantities with a minimal size of donor site, and have the potential to differentiate into a variety of cell types. Based on the observation that the specific keratinocyte markers p63 and desmoglein 3 are expressed in adipose-derived stromal/stem cells and that their expression is downregulated after the differentiation of these cells into adipocytes, we speculate that adipose-derived stromal/stem cells have the potential to differentiate into epithelial cells. Moreover, adipose-derived stromal/stem cells treated with retinoic acid and bone morphogenetic protein 4, and co-cultured with fibroblasts on type IV collagen have expressed approximately 8 times higher levels of desmoglein 3 and cytokeratin-5 expression. These findings indicated that suitable scaffolds, growth factors, or external environments are needed in clinical use of adipose-derived stromal/stem cells in treating skin diseases. Cultured adipose-derived stromal/stem cell preparations are heterogeneous and consist of different populations of stem and progenitor cells. For a more efficient induction of differentiation, cell sorting would be necessary, by selection for markers specific to the individual subpopulations. Adipose-derived stromal/stem cells play an increasingly important role as a source of transplantable cells in the treatment of several types of diseases including skin diseases. Further preclinical and clinical studies are needed to establish the efficient introduction of adipose-derived stromal/stem cells for the treatment of skin diseases or conditions.
{"title":"Adipose-derived stromal/stem cells as a potential source of skin regeneration","authors":"Toshio Hasegawa, S. Ikeda","doi":"10.14800/SCTI.787","DOIUrl":"https://doi.org/10.14800/SCTI.787","url":null,"abstract":"Adipose-derived stromal/stem cells are easily harvested in large quantities with a minimal size of donor site, and have the potential to differentiate into a variety of cell types. Based on the observation that the specific keratinocyte markers p63 and desmoglein 3 are expressed in adipose-derived stromal/stem cells and that their expression is downregulated after the differentiation of these cells into adipocytes, we speculate that adipose-derived stromal/stem cells have the potential to differentiate into epithelial cells. Moreover, adipose-derived stromal/stem cells treated with retinoic acid and bone morphogenetic protein 4, and co-cultured with fibroblasts on type IV collagen have expressed approximately 8 times higher levels of desmoglein 3 and cytokeratin-5 expression. These findings indicated that suitable scaffolds, growth factors, or external environments are needed in clinical use of adipose-derived stromal/stem cells in treating skin diseases. Cultured adipose-derived stromal/stem cell preparations are heterogeneous and consist of different populations of stem and progenitor cells. For a more efficient induction of differentiation, cell sorting would be necessary, by selection for markers specific to the individual subpopulations. Adipose-derived stromal/stem cells play an increasingly important role as a source of transplantable cells in the treatment of several types of diseases including skin diseases. Further preclinical and clinical studies are needed to establish the efficient introduction of adipose-derived stromal/stem cells for the treatment of skin diseases or conditions.","PeriodicalId":90974,"journal":{"name":"Stem cell and translational investigation","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66658537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Azadeh Anbarlou, A. Atashi, M. A. Rahnama, M. Soleimani, S. Kaviani
Different models were suggested for cancer development. One of them is cancer stem cell model. In this model, Invasion, relapse and resistance to anti-cancer drugs were seen in cancerous cells are related to these cells. Recently, weobserved that some of population in T-Acute lymphoblastic leukemia cell line display cancer stem cell properties. These cells were detected by CD133 marker. In vitro transwell assay showed that CD133 + Jurkat cells were more invasive than CD133 - Jurkat cells and also gene expression analysis confirmed CD133 + Jurkat cells expressed MMP9 gene in high levels. After treatment of CD133 + cells with doxorubicin, Annexin-PI staining showed that these cells have high resistance to chemotherapy drug. We demonstrated chemotherapy resistance may be because of up regulation of ABCG2 gene. In addition, CD133 + cells had unrestricted proliferation potential and were able to differentiate to cells with low growth potential (CD133 - ). Altogether; we demonstrated that CD133 could be as a marker to recognize cancer stem cells in Jurkat cell line.
{"title":"Cancer stem cells in acute lymphoblastic leukemia","authors":"Azadeh Anbarlou, A. Atashi, M. A. Rahnama, M. Soleimani, S. Kaviani","doi":"10.14800/SCTI.783","DOIUrl":"https://doi.org/10.14800/SCTI.783","url":null,"abstract":"Different models were suggested for cancer development. One of them is cancer stem cell model. In this model, Invasion, relapse and resistance to anti-cancer drugs were seen in cancerous cells are related to these cells. Recently, weobserved that some of population in T-Acute lymphoblastic leukemia cell line display cancer stem cell properties. These cells were detected by CD133 marker. In vitro transwell assay showed that CD133 + Jurkat cells were more invasive than CD133 - Jurkat cells and also gene expression analysis confirmed CD133 + Jurkat cells expressed MMP9 gene in high levels. After treatment of CD133 + cells with doxorubicin, Annexin-PI staining showed that these cells have high resistance to chemotherapy drug. We demonstrated chemotherapy resistance may be because of up regulation of ABCG2 gene. In addition, CD133 + cells had unrestricted proliferation potential and were able to differentiate to cells with low growth potential (CD133 - ). Altogether; we demonstrated that CD133 could be as a marker to recognize cancer stem cells in Jurkat cell line.","PeriodicalId":90974,"journal":{"name":"Stem cell and translational investigation","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66658524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In vertebrates, stem cells play a fundamental role in embryogenesis and lifetime homeostasis of adult tissues. The transcriptional regulator Cited2 is essential for many mouse developmental and morphological processes, and mutations in human CITED2 gene have repeatedly been associated with congenital heart defects. An increasing number of studies have now described the importance of Cited2 in self-renewal and cell fate decision of embryonic stem cells (ESC) and some adult stem cells. Interestingly, the loss of stem cell properties due to aging or extensive regeneration of some adult stem cells has been associated with a decrease of Cited2 expression, while an aberrant increase in CITED2 expression might play a critical role in malignant oncologic processes. Here, we review recent advances unravelling the complexity of Cited2 function as a regulator of the maintenance and cell fate decision of ESC and adult stem cells, and present its potential role in pathological conditions by modulating stem cells properties.
{"title":"Is CITED2 a general regulator of stem cell functions","authors":"J. Bragança, João M. A. Santos","doi":"10.14800/SCTI.755","DOIUrl":"https://doi.org/10.14800/SCTI.755","url":null,"abstract":"In vertebrates, stem cells play a fundamental role in embryogenesis and lifetime homeostasis of adult tissues. The transcriptional regulator Cited2 is essential for many mouse developmental and morphological processes, and mutations in human CITED2 gene have repeatedly been associated with congenital heart defects. An increasing number of studies have now described the importance of Cited2 in self-renewal and cell fate decision of embryonic stem cells (ESC) and some adult stem cells. Interestingly, the loss of stem cell properties due to aging or extensive regeneration of some adult stem cells has been associated with a decrease of Cited2 expression, while an aberrant increase in CITED2 expression might play a critical role in malignant oncologic processes. Here, we review recent advances unravelling the complexity of Cited2 function as a regulator of the maintenance and cell fate decision of ESC and adult stem cells, and present its potential role in pathological conditions by modulating stem cells properties.","PeriodicalId":90974,"journal":{"name":"Stem cell and translational investigation","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66658166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
I. Madabhavi, Gaurang Modi, Sandip Shah, A. Patel, A. Anand, H. Panchal, S. Parikh
Myelodysplastic syndrome (MDS) is heterogeneous hematopoietic stem cell disorders characterized by ineffective erythropoiesis and dyserythropoiesis. Allogenic HSCT from siblings in our country in pediatric MDS is very well documented. But HSCT from matched unrelated donor (MUD) in paediatric age is still a new concept to implement in our country. We are here presenting the relapse case of MDS (myelodysplastic syndrome) and we had done successful HSCT from MUD in a 14 year old paediatric patient. Myeloablative regimen (fludarabine, busulfan, cyclophosphamide, ATG) was used during HSCT. 100% donor chimerism was found on +day 34 VNTR study. Patient is doing well 1year after HSCT without any complications.
{"title":"Successful Hematopoietic stem cell transplantation (HSCT) from matched unrelated donor (MUD) in a pediatric patient using myeloablative regimen suffering from MDS: case report from western India.","authors":"I. Madabhavi, Gaurang Modi, Sandip Shah, A. Patel, A. Anand, H. Panchal, S. Parikh","doi":"10.14800/SCTI.738","DOIUrl":"https://doi.org/10.14800/SCTI.738","url":null,"abstract":"Myelodysplastic syndrome (MDS) is heterogeneous hematopoietic stem cell disorders characterized by ineffective erythropoiesis and dyserythropoiesis. Allogenic HSCT from siblings in our country in pediatric MDS is very well documented. But HSCT from matched unrelated donor (MUD) in paediatric age is still a new concept to implement in our country. We are here presenting the relapse case of MDS (myelodysplastic syndrome) and we had done successful HSCT from MUD in a 14 year old paediatric patient. Myeloablative regimen (fludarabine, busulfan, cyclophosphamide, ATG) was used during HSCT. 100% donor chimerism was found on +day 34 VNTR study. Patient is doing well 1year after HSCT without any complications.","PeriodicalId":90974,"journal":{"name":"Stem cell and translational investigation","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66658095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chun-Ting Lee, Abigail A. Kindberg, W. Freed, T. Su
Disorders of human neocortical development are particularly difficult to study by using animal models because of the marked complexity and unique features of the human cerebral cortex. Developmental effects of cocaine, as well as other drugs and toxins, are particularly challenging to study due to complicating factors such as variations in genetic background, time of exposure, and exposure to multiple substances. Studies aimed at elucidating the effects of cocaine on fetal brain development have used rodent cell lines, primary human cells, and rat models to show that cocaine metabolism by cytochrome P450 results in oxidative ER stress and subsequent impairment of neural progenitor cell proliferation. Recently, in vitro models of neocortical development have been generated by using pluripotent stem cells. One such model, utilizing human pluripotent stem cells, reproduced the formation of neocortical glutamatergic and GABAergic neurons on radial glial scaffolding structure in a temporally sensitive manner mimicking human in vivo neocortical development. Cocaine exposure resulted in the accumulation of reactive oxygen species (ROS), premature neuronal differentiation, accelerated generation of deep-layer and upper-layer glutamatergic projection neurons, and increased formation of GABAergic interneurons. Each of these changes was inhibited by the cytochrome P450 inhibitor cimetidine. These studies suggest that, in the developing human cerebral cortex, cocaine metabolism through cytochrome P450-dependent ROS generation leads to premature neuronal differentiation of neocortical progenitors and impaired neocortical patterning.
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