Thursday, September 24, 2009

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WPI receives $1.3 million in federal awards for ongoing research in the life sciences
September 24, 2009 at 3:18 pm


Reportlinker Adds Stem Cell Therapeutics Markets Report
September 24, 2009 at 12:03 pm


Stem cell applications and research highlight NJIT's first Research Cafe
September 24, 2009 at 12:03 pm


Gravity, a regulation factor in the differentiation of rat bone marrow mesenchymal stem cells.
September 24, 2009 at 9:35 am

Related Articles

Gravity, a regulation factor in the differentiation of rat bone marrow mesenchymal stem cells.

J Biomed Sci. 2009 Sep 21;16(1):87

Authors: Huang Y, Dai ZQ, Ling SK, Zhang HY, Wan YM, Li YH

ABSTRACT: Stem cell therapy has emerged as a potential therapeutic option for tissue engineering and regenerative medicine, but many issues remain to be resolved, such as the amount of seed cells, committed differentiation and the efficiency. Several previous studies have focused on the study of chemical inducement microenvironments. In the present study, we investigated the effects of gravity on the differentiation of bone marrow mesenchymal stem cells (BMSCs) into force-sensitive or force-insensitive cells. Methods and results Rat BMSCs (rBMSCs) were cultured under hypergravity or simulated microgravity (SMG) conditions with or without inducement medium. The expression levels of the characteristic proteins were measured and analyzed using immunocytochemical, RT-PCR and Western-blot analyses. After treatment with 5-azacytidine and hypergravity, rBMSCs expressed more characteristic proteins of cardiomyocytes such as cTnT, GATA4 and beta-MHC; however, fewer such proteins were seen with SMG. After treating rBMSCs with osteogenic inducer and hypergravity, there were marked increases in the expression levels of ColIA1, Cbfa1 and ALP. Reverse results were obtained with SMG. rBMSCs treated with adipogenic inducer and SMG expressed greater levels of PPARgamma. Greater levels of Cbfa1- or cTnT-positive cells were observed under hypergravity without inducer, as shown by FACS analysis. These results indicate that hypergravity induces differentiation of rBMSCs into force-sensitive cells (cardiomyocytes and osteoblasts), whereas SMG induces force-insensitive cells (adipocytes). CONCLUSIONS: Taken together, we conclude that gravity is an important factor affecting the differentiation of rBMSCs; this provides a new avenue for mechanistic studies of stem cell differentiation and a new approach to obtain more committed differentiated or undifferentiated cells.

PMID: 19772591 [PubMed - as supplied by publisher]


Effect of Electromechanical Stimulation on the Maturation of Myotubes on Aligned Electrospun Fibers.
September 24, 2009 at 8:48 am

Effect of Electromechanical Stimulation on the Maturation of Myotubes on Aligned Electrospun Fibers.

Cell Mol Bioeng. 2008 Sep 1;1(2-3):133-145

Authors: Liao IC, Liu JB, Bursac N, Leong KW

Tissue engineering may provide an alternative to cell injection as a therapeutic solution for myocardial infarction. A tissue-engineered muscle patch may offer better host integration and higher functional performance. This study examined the differentiation of skeletal myoblasts on aligned electrospun polyurethane (PU) fibers and in the presence of electromechanical stimulation. Skeletal myoblasts cultured on aligned PU fibers showed more pronounced elongation, better alignment, higher level of transient receptor potential cation channel-1 (TRPC-1) expression, upregulation of contractile proteins and higher percentage of striated myotubes compared to those cultured on random PU fibers and film. The resulting tissue constructs generated tetanus forces of 1.1 mN with a 10-ms time to tetanus. Additional mechanical, electrical, or synchronized electromechanical stimuli applied to myoblasts cultured on PU fibers increased the percentage of striated myotubes from 70 to 85% under optimal stimulation conditions, which was accompanied by an upregulation of contractile proteins such as alpha-actinin and myosin heavy chain. In describing how electromechanical cues can be combined with topographical cue, this study helped move towards the goal of generating a biomimetic microenvironment for engineering of functional skeletal muscle.

PMID: 19774099 [PubMed - as supplied by publisher]


Gravity, a regulation factor in the differentiation of rat bone marrow mesenchymal stem cells.
September 24, 2009 at 8:48 am

Gravity, a regulation factor in the differentiation of rat bone marrow mesenchymal stem cells.

J Biomed Sci. 2009 Sep 21;16(1):87

Authors: Huang Y, Dai ZQ, Ling SK, Zhang HY, Wan YM, Li YH

ABSTRACT: Stem cell therapy has emerged as a potential therapeutic option for tissue engineering and regenerative medicine, but many issues remain to be resolved, such as the amount of seed cells, committed differentiation and the efficiency. Several previous studies have focused on the study of chemical inducement microenvironments. In the present study, we investigated the effects of gravity on the differentiation of bone marrow mesenchymal stem cells (BMSCs) into force-sensitive or force-insensitive cells. Methods and results Rat BMSCs (rBMSCs) were cultured under hypergravity or simulated microgravity (SMG) conditions with or without inducement medium. The expression levels of the characteristic proteins were measured and analyzed using immunocytochemical, RT-PCR and Western-blot analyses. After treatment with 5-azacytidine and hypergravity, rBMSCs expressed more characteristic proteins of cardiomyocytes such as cTnT, GATA4 and beta-MHC; however, fewer such proteins were seen with SMG. After treating rBMSCs with osteogenic inducer and hypergravity, there were marked increases in the expression levels of ColIA1, Cbfa1 and ALP. Reverse results were obtained with SMG. rBMSCs treated with adipogenic inducer and SMG expressed greater levels of PPARgamma. Greater levels of Cbfa1- or cTnT-positive cells were observed under hypergravity without inducer, as shown by FACS analysis. These results indicate that hypergravity induces differentiation of rBMSCs into force-sensitive cells (cardiomyocytes and osteoblasts), whereas SMG induces force-insensitive cells (adipocytes). CONCLUSIONS: Taken together, we conclude that gravity is an important factor affecting the differentiation of rBMSCs; this provides a new avenue for mechanistic studies of stem cell differentiation and a new approach to obtain more committed differentiated or undifferentiated cells.

PMID: 19772591 [PubMed - as supplied by publisher]


Quantitative MRI assessment of matrix development in cell-seeded natural urinary bladder smooth muscle tissue-engineered constructs.
September 24, 2009 at 8:48 am

Quantitative MRI assessment of matrix development in cell-seeded natural urinary bladder smooth muscle tissue-engineered constructs.

Tissue Eng Part C Methods. 2009 Sep 22;

Authors: Cheng HL, Islam SS, Loai Y, Antoon R, Beaumont M, Farhat WA

The approach of cell-seeded natural scaffolds holds great promise for tissue-engineering complicated soft-tissue organs such as the urinary bladder and heart. However, relatively little is known about cell-natural scaffold interactions or their influence on magnetic resonance image (MRI) characterization, which is valuable for non-invasive monitoring. Ideally, MRI should provide information on tissue biochemistry in addition to structure and function. In this study, quantitative MRI was performed on control and smooth muscle cell-seeded natural bladder matrices at different time-points up to 7 days post-seeding. Measurements of MR relaxation times (T1, T2) and diffusion coefficient (D) showed an overall change that was incompatible with cell presence. Multicomponent T2 provided greater specificity, revealing time-course changes in the short T2 fraction that were consistent with biochemically determined matrix degradation from collagenase released from seeded cells. These matrix alterations are noted for the first time, and their relatively early occurrence may be unique to soft tissue matrices compared with synthetic materials. More importantly, they are not evident on histology but are revealed on quantitative MRI. We conclude that quantitative MRI may provide specific information on cell-matrix interaction and is a promising non-invasive approach to understand and monitor cell-seeded natural scaffold-based regeneration.

PMID: 19772478 [PubMed - as supplied by publisher]


Role of nano-fibrous poly(caprolactone) scaffolds on human mesenchymal stem cell attachment and spreading for in vitro bone tissue engineering-response to osteogenic regulators.
September 24, 2009 at 8:48 am

Role of nano-fibrous poly(caprolactone) scaffolds on human mesenchymal stem cell attachment and spreading for in vitro bone tissue engineering-response to osteogenic regulators.

Tissue Eng Part A. 2009 Sep 22;

Authors: N S B, Menon D, Nagarajan S, K T S, Stephen S, Mony U, Rangasamy J, Nair S

In the present study, we evaluated the role of fiber size scale on the adhesion and spreading potential of human mesenchymal stem cells (hMSCs) on electrospun poly(caprolactone) (PCL) nano and micro-fibrous scaffolds. The effect of in vivo regulators in inducing osteogenic differentiation of hMSCs on PCL nano-fibrous scaffolds were investigated using osteogenic differentiation marker gene expression and matrix mineralization. Here, we report for the first time, the influence of in vivo regulators in an in vitro setting with hMSCs for bone tissue engineering on PCL nano-fibrous matrices. Our results indicated that hMSCs attached and spread rapidly on nano-fibrous scaffolds in comparison to micro-fibrous PCL. Furthermore, hMSCs proliferated well on the nano-fibrous scaffolds. The cells on the nano-fibrous PCL were found to differentiate into the osteoblast lineage and subsequently mineralize upon addition of in vivo osteogenic regulators. The attachment and spreading of hMSCs were more effective on the nano-fibers compared to the micro-fibers despite the lower protein surface coverage (total adsorbed protein per unit fiber surface area) on nano-fibers.

PMID: 19772455 [PubMed - as supplied by publisher]


The effect of insulin-loaded chitosan particle aggregated scaffolds in chondrogenic differentiation.
September 24, 2009 at 8:48 am

The effect of insulin-loaded chitosan particle aggregated scaffolds in chondrogenic differentiation.

Tissue Eng Part A. 2009 Sep 22;

Authors: Malafaya PB, Oliveira JT, Reis RL

Osteochondral defects repair requires a tissue engineering approach which aims at mimicking the physiological properties and structure of two different tissues (cartilage and bone) using a scaffold-cell construct. One ideal approach would be to engineer in-vitro a hybrid material using a single cell source. For that purpose, the scaffold should be able to provide the adequate biochemical cues in order to promote the selective but simultaneous differentiation of both tissues. In this work, attention was paid primarily to the chondrogenic differentiation by focusing on the development of polymeric systems that provide biomolecules release in order to induce chondrogenic differentiation. For that, different formulations of insulin-loaded chitosan particle aggregated scaffolds were developed as a potential model system for cartilage and osteochondral tissue engineering applications using insulin as a potent bioactive substance known to induce chondrogenic differentiation. The insulin encapsulation efficiency was shown to be high with values of 70.37%+/-0.8, 84.26%+/-1.76 and 87.23%+/-1.58 for loadings of 0.05%, 0.5 and 5%, respectively. The in-vitro release profiles were assessed in physiological conditions mimicking the cell culture procedures and quantified by Micro-BCA protein assay. Different release profiles were obtained that showed to be dependent on the initial insulin loading percentage. Furthermore, the effect on pre-chondrogenic ATDC5 cells was investigated for periods up to 4 weeks by studying the influence of these release systems on cells morphology, DNA and GAGs content, histology and gene expression of collagen type I and II, Sox-9 and aggrecan assessed by realtime-PCR. When compared to control conditions (unloaded scaffolds cultured with standard chondrogenic-inducing medium), insulin-loaded scaffolds upregulated the Sox-9 and aggrecan expression after 4 weeks of culture. From the overall results, it is reasonable to conclude that the developed loaded scaffolds when seeded with ATDC5 can provide biochemical cues for chondrogenic differentiation. Among the tested formulations, the higher insulin loaded system (5%) was the most effective in promoting chondrogenic differentiation.

PMID: 19772454 [PubMed - as supplied by publisher]


Current status and perspectives of cell therapy in Chagas disease.
September 24, 2009 at 8:48 am

Current status and perspectives of cell therapy in Chagas disease.

Mem Inst Oswaldo Cruz. 2009 Jul;104 Suppl 1:325-32

Authors: Soares MB, dos Santos RR

One century after its discovery, Chagas disease, caused by the protozoan, Trypanosoma cruzi, remains a major health problem in Latin America. Mortality and morbidity are mainly due to chronic processes that lead to dysfunction of the cardiac and digestive systems. About one third of the chronic chagasic individuals have or will develop the symptomatic forms of the disease, with cardiomyopathy being the most common chronic form. This is a progressively debilitating disease for which there are no currently available effective treatments other than heart transplantation. Like in other cardiac diseases, tissue engineering and cell therapy have been investigated in the past few years as a means of recovering the heart function lost as a consequence of chronic damage caused by the immune-mediated pathogenic mechanisms elicited in individuals with chronic chagasic cardiomyopathy. Here we review the studies of cell therapy in animal models and patients with chronic Chagas disease and the perspectives of the recovery of the heart function lost due to infection with T. cruzi.

PMID: 19753492 [PubMed - in process]


Generating ears from cultured autologous auricular chondrocytes by using two-stage implantation in treatment of microtia.
September 24, 2009 at 8:48 am

Related Articles

Generating ears from cultured autologous auricular chondrocytes by using two-stage implantation in treatment of microtia.

Plast Reconstr Surg. 2009 Sep;124(3):817-25

Authors: Yanaga H, Imai K, Fujimoto T, Yanaga K

BACKGROUND: Microtia is a congenital ear hypoplasia associated with auricular defects. Conventional treatment involves implanted costal cartilage. The impact of surgical invasion and donor-site morbidity can be particularly severe in pediatric patients, and the collectable volume of autologous cartilage is limited. The authors therefore developed a new technique for microtia and applied it to treat four patients. METHODS: Through the development of a multilayer chondrocyte culture system and two-stage implantation technique, the authors successfully generated human ears. In culture, the chondrocytes are expanded to a sufficiently large volume, produce rich chondroid matrix, and form immature cartilaginous tissues. In the authors' two-stage implantation, the cultured chondrocytes are injection-implanted into the lower abdomen of the patient, where the cells grow into a large, newly generated cartilage with neoperichondrium in 6 months. This cartilage is harvested surgically, sculptured into an ear framework, and implanted subcutaneously into the position of the new ear. RESULTS: The cultured chondrocytes formed a mature cartilage block with sufficient elasticity for use as an auricular cartilage. The formed block had the same histologic origin as elastic cartilage. The ear framework produced from this block was implanted into the auricular defect area, and an auricle with a smooth curvature and shape was subsequently configured. In the 2 to 5 years of postoperative monitoring, the neocartilage maintained good shape, without absorption. CONCLUSIONS: The authors' four patients are the first successful cases of regenerative surgery for microtia using cultured ear chondrocytes. The benefits of the technique include minimal surgical invasion, lower donor-site morbidity, lessened chance of immunologic rejection, and implantation stability.

PMID: 19730300 [PubMed - indexed for MEDLINE]


Expression profiles of phases 1 and 2 metabolizing enzymes in human skin and the reconstructed skin models Episkin and full thickness model from Episkin.
September 24, 2009 at 8:48 am

Related Articles

Expression profiles of phases 1 and 2 metabolizing enzymes in human skin and the reconstructed skin models Episkin and full thickness model from Episkin.

J Steroid Biochem Mol Biol. 2009 Sep;116(3-5):178-86

Authors: Luu-The V, Duche D, Ferraris C, Meunier JR, Leclaire J, Labrie F

BACKGROUND: Episkin and full thickness model from Episkin (FTM) are human skin models obtained from in vitro growth of keratinocytes into the five typical layers of the epidermis. FTM is a full thickness reconstructed skin model that also contains fibroblasts seeded in a collagen matrix. OBJECTIVES: To assess whether enzymes involved in chemical detoxification are expressed in Episkin and FTM and how their levels compare with the human epidermis, dermis and total skin. METHODS: Quantification of the mRNA expression levels of phases 1 and 2 metabolizing enzymes in cultured Episkin and FTM and human epidermis, dermis and total skin using Realtime PCR. RESULTS: The data show that the expression profiles of 61 phases 1 and 2 metabolizing enzymes in Episkin, FTM and epidermis are generally similar, with some exceptions. Cytochrome P450-dependent enzymes and flavin monooxygenases are expressed at low levels, while phase 2 metabolizing enzymes are expressed at much higher levels, especially, glutathione-S-transferase P1 (GSTP1) catechol-O-methyl transferase (COMT), steroid sulfotransferase (SULT2B1b), and N-acetyl transferase (NAT5). The present study also identifies the presence of many enzymes involved in cholesterol, arachidonic acid, leukotriene, prostaglandin, eicosatrienoic acids, and vitamin D3 metabolisms. CONCLUSION: The present data strongly suggest that Episkin and FTM represent reliable and valuable in vitro human skin models for studying the function of phases 1 and 2 metabolizing enzymes in xenobiotic metabolisms. They could be used to replace invasive methods or laboratory animals for skin experiments.

PMID: 19482084 [PubMed - indexed for MEDLINE]


The effect of adipose-derived stem cells on ischemia-reperfusion injury: immunohistochemical and ultrastructural evaluation.
September 24, 2009 at 8:23 am

Related Articles

The effect of adipose-derived stem cells on ischemia-reperfusion injury: immunohistochemical and ultrastructural evaluation.

Plast Reconstr Surg. 2009 Sep;124(3):804-15

Authors: Uysal AC, Mizuno H, Tobita M, Ogawa R, Hyakusoku H

BACKGROUND: Advances in the treatment of reperfusion injury have created an opportunity for plastic surgeons to apply these treatments to flaps and implanted tissues. The authors examined the direct and indirect effects of adipose-derived stem cells on ischemia-reperfusion injury on a skin flap model to determine the in vivo differentiation of adipose-derived stem cells to endothelial cells; the levels of vascular endothelial growth factor (VEGF), transforming growth factor-beta, and fibroblast growth factor; and the ultrastructural changes apparent with scanning electron microscopy to clarify the initial events and the following cascades. METHODS: Two identical cranial based random flaps with a dimension of 1 x 5 cm were elevated on the dorsums of 20 ICR mice. The left flap was designated as the control and the right flap was injected with adipose-derived stem cells. The flaps were then subjected to 6 hours of ischemia by clamping the pedicle, and then reperfusion. RESULTS: The mean viable flap length in the control and experimental groups was 15.2 +/- 3.4 mm and 24.4 +/- 2.9 mm, respectively. The mean viable flap area in the control and experimental groups was 12.9 +/- 4.1 mm and 21.8 +/- 3.7 mm, respectively. The in vivo differentiation of adipose-derived stem cells to endothelial cells was observed. The immunohistochemical stainings, VEGF, transforming growth factor-beta, and fibroblast growth factor revealed increased levels in the experimental groups. Scanning electron microscopy indicated mild injury in the experimental group. CONCLUSIONS: The adipose-derived stem cells could prevent ischemia-reperfusion injury, mainly by regulating the growth factors. Although VEGF was the foremost inhibitor of injury, the overall cascade was enhanced by adipose-derived stem cells, with the help of the other growth factors.

PMID: 19730299 [PubMed - indexed for MEDLINE]


Human embryonic stem cells are pre-mitotically committed to self-renewal and acquire a lengthened G1 phase upon lineage programming.
September 24, 2009 at 6:35 am

Human embryonic stem cells are pre-mitotically committed to self-renewal and acquire a lengthened G1 phase upon lineage programming.

J Cell Physiol. 2009 Sep 22;

Authors: Becker KA, Stein JL, Lian JB, van Wijnen AJ, Stein GS

Self-renewal of human embryonic stem (hES) cells proceeds by a unique abbreviated cell cycle with a shortened G1 phase and distinctions in molecular cell cycle regulatory parameters. In this study, we show that early lineage-commitment of pluripotent hES cells modifies cell cycle kinetics. Human ES cells acquire a lengthened G1 within 72 h after lineage-programming is initiated, as reflected by loss of the pluripotency factor Oct4 and alterations in nuclear morphology. In hES cells that maintain the pristine pluripotent state, we find that autocrine mechanisms contribute to sustaining the abbreviated cell cycle. Our data show that naïve and mitotically synchronized pluripotent hES cells are competent to initiate two consecutive S phases in the absence of external growth factors. We conclude that short-term self-renewal of pluripotent hES cells occurs autonomously, in part due to secreted factors, and that pluripotency is functionally linked to the abbreviated hES cell cycle. J. Cell. Physiol. (c) 2009 Wiley-Liss, Inc.

PMID: 19774559 [PubMed - as supplied by publisher]


Using zebrafish to assess the impact of drugs on neural development and function.
September 24, 2009 at 6:35 am

Using zebrafish to assess the impact of drugs on neural development and function.

Expert Opin Drug Discov. 2009 Jul 1;4(7):715-726

Authors: Guo S

BACKGROUND: Zebrafish is becoming an increasingly attractive model organism for understanding biology and developing therapeutics, because as a vertebrate, it shares considerable similarity with mammals in both genetic compositions and tissue/organ structures, and yet remains accessible to high throughput phenotype-based genetic and small molecule compound screening. OBJECTIVE/METHOD: The focus of this review is on the nervous system, which is arguably the most complex organ and known to be afflicted by more than six hundred disorders in humans. I discuss the past, present, and future of using zebrafish to assess the impact of small molecule drugs on neural development and function, in light of understanding and treating neurodevelopmental disorders such as autism, neurodegenerative disorders including Alzheimer's, Parkinson's, and Hungtington's disease, and neural system dysfunctions such as anxiety/depression and addiction. CONCLUSION: These studies hold promise to reveal fundamental mechanisms governing nervous system development and function, and to facilitate small molecule drug discovery for the many types of neurological disorders.

PMID: 19774094 [PubMed - as supplied by publisher]


Enhanced generation of induced pluripotent stem cells from a subpopulation of human fibroblasts.
September 24, 2009 at 6:35 am

Enhanced generation of induced pluripotent stem cells from a subpopulation of human fibroblasts.

PLoS One. 2009;4(9):e7118

Authors: Byrne JA, Nguyen HN, Reijo Pera RA

BACKGROUND: The derivation of induced pluripotent stem cells (iPSCs) provides new possibilities for basic research and novel cell-based therapies. Limitations, however, include our current lack of understanding regarding the underlying mechanisms and the inefficiency of reprogramming. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report identification and isolation of a subpopulation of human dermal fibroblasts that express the pluripotency marker stage specific embryonic antigen 3 (SSEA3). Fibroblasts that expressed SSEA3 demonstrated an enhanced iPSC generation efficiency, while no iPSC derivation was obtained from the fibroblasts that did not express SSEA3. Transcriptional analysis revealed NANOG expression was significantly increased in the SSEA3 expressing fibroblasts, suggesting a possible mechanistic explanation for the differential reprogramming. CONCLUSIONS/SIGNIFICANCE: To our knowledge, this study is the first to identify a pluripotency marker in a heterogeneous population of human dermal fibroblasts, to isolate a subpopulation of cells that have a significantly increased propensity to reprogram to pluripotency and to identify a possible mechanism to explain this differential reprogramming. This discovery provides a method to significantly increase the efficiency of reprogramming, enhancing the feasibility of the potential applications based on this technology, and a tool for basic research studies to understand the underlying reprogramming mechanisms.

PMID: 19774082 [PubMed - in process]


Stem cells in acute kidney injury repair.
September 24, 2009 at 6:35 am

Stem cells in acute kidney injury repair.

Minerva Urol Nefrol. 2009 Sep;61(3):205-13

Authors: Tögel F, Westenfelder C

New discoveries and developments in the biology and propagation of stem cells have fueled a whole new field of Medicine that has sparked great interest in the scientific community as well as in the general media and public. Stem cells are a very prominent and debated topic and have given ground to a new field of therapy in Medicine, which is called Regenerative Medicine. The kidney is a highly sophisticated and complicated organ, yet stem cell therapies have become of interest to Nephrologists and promising animal data are available showing the use of different stem cell populations in Nephrology. Acute kidney injury (AKI) is a clinical entity caused by a variety of factors resulting in renal damage and loss of function. Although it is reversible up to a point, it contributes tremendously to hospital morbidity and mortality. At the current time there are only supportive treatments available. Stem cell based therapies have the potential to become a broader and diverse treatment approach that is tailored to the pathophysiology of the disease and is therefore potentially more effective than traditional pharmacological approaches. The current article gives an overview about the field in general as well as potential treatment approaches and mechanisms.

PMID: 19773723 [PubMed - in process]


Acting Locally and Globally: Myc's Ever-Expanding Roles on Chromatin.
September 24, 2009 at 6:35 am

Acting Locally and Globally: Myc's Ever-Expanding Roles on Chromatin.

Cancer Res. 2009 Sep 22;

Authors: Varlakhanova NV, Knoepfler PS

Myc regulates key cellular processes including cell cycle, differentiation, and apoptosis. It has long been thought to direct these functions by acting solely as a classic transcription factor regulating expression of a small number of key target genes through discrete chromatin events in their promoters. A recent wave of genomics studies together directly challenge the narrowness of this model. For example, Myc binds to tens of thousands of sites in the human genome. It also regulates histone acetylation at and transcription of a remarkable number of genes, far beyond that expected of a classical transcription factor. The influence of Myc on chromatin also surprisingly extends to both genic and expansive intergenic regions. These studies support an evolving model in which Myc activity on chromatin is far more complex than previously imagined. The ability of Myc to act both locally and globally on chromatin may be responsible for its wide-ranging effects on the biology of stem and tumor cells. [Cancer Res 2009;69(19):7487-90].

PMID: 19773445 [PubMed - as supplied by publisher]


Gravity, a regulation factor in the differentiation of rat bone marrow mesenchymal stem cells.
September 24, 2009 at 6:35 am

Gravity, a regulation factor in the differentiation of rat bone marrow mesenchymal stem cells.

J Biomed Sci. 2009 Sep 21;16(1):87

Authors: Huang Y, Dai ZQ, Ling SK, Zhang HY, Wan YM, Li YH

ABSTRACT: Stem cell therapy has emerged as a potential therapeutic option for tissue engineering and regenerative medicine, but many issues remain to be resolved, such as the amount of seed cells, committed differentiation and the efficiency. Several previous studies have focused on the study of chemical inducement microenvironments. In the present study, we investigated the effects of gravity on the differentiation of bone marrow mesenchymal stem cells (BMSCs) into force-sensitive or force-insensitive cells. Methods and results Rat BMSCs (rBMSCs) were cultured under hypergravity or simulated microgravity (SMG) conditions with or without inducement medium. The expression levels of the characteristic proteins were measured and analyzed using immunocytochemical, RT-PCR and Western-blot analyses. After treatment with 5-azacytidine and hypergravity, rBMSCs expressed more characteristic proteins of cardiomyocytes such as cTnT, GATA4 and beta-MHC; however, fewer such proteins were seen with SMG. After treating rBMSCs with osteogenic inducer and hypergravity, there were marked increases in the expression levels of ColIA1, Cbfa1 and ALP. Reverse results were obtained with SMG. rBMSCs treated with adipogenic inducer and SMG expressed greater levels of PPARgamma. Greater levels of Cbfa1- or cTnT-positive cells were observed under hypergravity without inducer, as shown by FACS analysis. These results indicate that hypergravity induces differentiation of rBMSCs into force-sensitive cells (cardiomyocytes and osteoblasts), whereas SMG induces force-insensitive cells (adipocytes). CONCLUSIONS: Taken together, we conclude that gravity is an important factor affecting the differentiation of rBMSCs; this provides a new avenue for mechanistic studies of stem cell differentiation and a new approach to obtain more committed differentiated or undifferentiated cells.

PMID: 19772591 [PubMed - as supplied by publisher]


Phenotypic indications that human sweat glands are a rich source of nestin positive stem cell populations.
September 24, 2009 at 6:35 am

Phenotypic indications that human sweat glands are a rich source of nestin positive stem cell populations.

Br J Dermatol. 2009 Sep 22;

Authors: Petschnik AE, Klatte JE, Evers LH, Kruse C, Paus R, Danner S

Summary Background We have recently shown that the expression of nestin, a progenitor/stem cell marker protein, is localized to different, mesenchymal compartments in human skin including the sweat gland stroma. Objectives Since other exocrine glands are recognized sources of multipotent stem cell populations with multilineage differentiation potential, it was our aim to isolate, expand and characterize glandular stem cells from human sweat glands. Methods Isolation of human sweat glands was based on mechanical and enzymatical digestion of axillary skin. Cultivation was performed on collagen-coated cell culture dishes and the resulted cell population was investigated on protein and mRNA level. Results Outgrowing cells of isolated sweat glands showed a high proliferation activity and were characterized by nestin expression in more than 80% of the cells. These sweat gland stem cells could be maintained in culture for long periods of time and showed spontanous differentiation into cells representative for the different germ layers. Conclusions This pilot study provides the first, simple protocol for the isolation of adult human nestin positive (nestin(+)) stem cells from the sweat gland mesenchyme, which promises to provide an easily accessible and abundantly available, autologous source of multipotent stem cells for cell-based regenerative medicine applications.

PMID: 19772523 [PubMed - as supplied by publisher]


Duke biomedical scientists win 2 highly prized NIH Director's Awards
September 24, 2009 at 1:30 am

 

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