Wednesday, March 31, 2010

4/1 TE-RegenMed-StemCell feed

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Stem cell therapy to tackle HIV
March 31, 2010 at 8:24 PM

 

LSU researcher receives grant to study equine adult stem cells
March 31, 2010 at 12:23 PM

 

International Stem Cell (ISCO) Announces the Signing of a Distribution Agreement with Veritas Corporation, Opening Japanese Markets for Its Lifeline Cell Technology® Brand of Human Cell Culture Products
March 31, 2010 at 9:23 AM

 

Stem cells for myocardial repair.
March 31, 2010 at 9:09 AM

Stem cells for myocardial repair.

Thromb Haemost. 2010 Mar 29;104(1)

Authors: Siu CW, Liao SY, Liu Y, Lian Q, Tse HF

There is a growing interest in the clinical application for stem cell as a novel therapy for treatment of acute myocardial infarction and chronic myocardial ischaemia. The initial premise is the transplanted exogenous stem cells can engraft and integrate with host myocardium for cardiac regeneration. However, recent experimental studies suggest that multiple mechanisms, including remodelling of extracellular matrix, enhancement of neovascularisation and recruitment of endogenous stem cells are more likely to contribute to the beneficial effects of stem cell therapy that direct trans-differentiation of stem cells into functional myocardium. Among different potential cell sources, bone marrow-derived cells and skeletal myoblasts have been tested in pilot clinical trials. Phase I/II randomised controlled clinical trials suggest that intracoronary or intramyocardial injection of bone marrow-derived cells may be safe and feasible strategies for treatment of acute myoca! rdial infarction as well as chronic myocardial ischaemia. In addition, these studies show a modest, but significant improvement in left ventricular ejection fraction and clinical status of patients after cell transplantation. Nevertheless, most of these studies included a relatively small sample size (<200) and short duration of follow-up (<6 months), and the clinical efficacy of stem cell therapy need to be confirmed by future clinical trials. Furthermore, the optimal timing, cell types and mode of delivery need to be addressed, and strategies to improve cell survival and engraftment should also be developed to overcome the potential hurdles related to cell-based therapy.

PMID: 20352151 [PubMed - as supplied by publisher]

 

Effects of Adipose Tissue-Derived Stem Cell Therapy After Myocardial Infarction: Impact of the Route of Administration.
March 31, 2010 at 9:09 AM

Effects of Adipose Tissue-Derived Stem Cell Therapy After Myocardial Infarction: Impact of the Route of Administration.

J Card Fail. 2010 Apr;16(4):357-366

Authors: Rigol M, Solanes N, Farré J, Roura S, Roqué M, Berruezo A, Bellera N, Novensà L, Tamborero D, Prat-Vidal C, Huzman MA, Batlle M, Hoefsloot M, Sitges M, Ramírez J, Dantas AP, Merino A, Sanz G, Brugada J, Bayés-Genís A, Heras M

BACKGROUND: Cell-based therapies offer a promising approach to reducing the short-term mortality rate associated with heart failure after a myocardial infarction. The aim of the study was to analyze histological and functional effects of adipose tissue-derived stem cells (ADSCs) after myocardial infarction and compare 2 types of administration pathways. METHODS AND RESULTS: ADSCs from 28 pigs were labeled by transfection. Animals that survived myocardial infarction (n = 19) received: intracoronary culture media (n = 4); intracoronary ADSCs (n = 5); transendocardial culture media (n = 4); or transendocardial ADSCs (n = 6). At 3 weeks' follow-up, intracoronary and transendocardial administration of ADSCs resulted in similar rates of engrafted cells (0.85 [0.19-1.97] versus 2 [1-2] labeled cells/cm(2), respectively; P = NS) and some of those cells expressed smooth muscle cell markers. The intracoronary administration of ADSCs was more effective in increasing the ! number of small vessels than transendocardial administration (223 +/- 40 versus 168 +/- 35 vessels/mm(2); P < .05). Ejection fraction was not modified by stem cell therapy. CONCLUSIONS: This is the first study to compare intracoronary and transendocardial administration of autologous ADSCs in a porcine model of myocardial infarction. Both pathways of ADSCs delivery are feasible, producing a similar number of engrafted and differentiated cells, although intracoronary administration was more effective in increasing neovascularization.

PMID: 20350704 [PubMed - as supplied by publisher]

 

Adipose Stem Cells for Soft Tissue Regeneration.
March 31, 2010 at 6:37 AM

Adipose Stem Cells for Soft Tissue Regeneration.

Handchir Mikrochir Plast Chir. 2010 Apr;42(2):124-128

Authors: Brayfield C, Marra K, Rubin JP

Adipose-derived stem cells (ASCs) can be isolated from human adipose tissue with the exceptional potential for differentiation into mature adipocytes. Utilization of this system is very promising in developing improved techniques to repair soft tissue defects. Current reconstructive procedures, especially after trauma and oncological surgery, transfer autologous soft tissue grafts having limitations. However, ASCs offer the ability to either generate soft tissue with no donor-site morbidity (with the exception of a minor loss of adipose tissue) or enhance the viability and durability of other grafts. This review will discuss the relevant properties of human adult adipose-derived stem cells for the regeneration of adipose tissue. Discussion will focus on the biology of ASCs, cell delivery vehicles/scaffolds useful in applying ASCs as a therapy, and suitable IN VIVO animal models for studying adipose tissue engineering. Also included is a description of the current ! clinical studies with ASCs in Europe and Asia.

PMID: 20352575 [PubMed - as supplied by publisher]

 

Tailoring the morphology of high molecular weight PLLA scaffolds through bioglass additions.
March 31, 2010 at 6:37 AM

Tailoring the morphology of high molecular weight PLLA scaffolds through bioglass additions.

Acta Biomater. 2010 Mar 26;

Authors: Barroca N, Daniel-da-Silva AL, Vilarinho PM, Fernandes MH

Thermally induced phase separation (TIPS) has been used in the last years to prepare porous structures for tissue engineering applications and particular attention has been paid to the increase of pore size without the use of possible toxic surfactants. Within this context, an alternative method to control the porosity of polymeric scaffolds via the combination with a bioglass is proposed in this work. By the addition of a bioactive glass from the 3CaO.P(2)O(5)-MgO-SiO(2) system, the porous structure of high molecular weight poly (L-lactic) acid (PLLA) scaffolds prepared by TIPS is tailored. Bioglass acts as a nucleating catalyst agent of the PLLA matrix promoting its crystallization and the glass solubility controls the pore size. A significant increase of the pore size is observed as the BG content increases and scaffolds with large pore size (ca. 150mum) can be prepared. In addition, the bioactive character of the scaffolds is proved by in vitro tests in synthe! tic plasma. The importance of this approach resides on the combination of the ability to tailor the porosity of polymeric scaffolds via the tunable solubility of bioglasses, without the use of toxic surfactants, leading to a composite structure with suitable properties for bone tissue engineering applications.

PMID: 20350622 [PubMed - as supplied by publisher]

 

Evaluation of Mesoporous Silicon / Polycaprolactone Composites as Ophthalmic Implants.
March 31, 2010 at 6:37 AM

Evaluation of Mesoporous Silicon / Polycaprolactone Composites as Ophthalmic Implants.

Acta Biomater. 2010 Mar 26;

Authors: Kashanian S, Harding F, Irani Y, Klebe S, Marshall K, Loni A, Canham L, Fan D, Williams KA, Voelcker NH, Coffer JL

The suitability of mesoporous silicon encapsulated in microfibers of the biodegradable polymer polycaprolactone (PCL) for ophthalmic applications was evaluated, using both a cell attachment assay with epithelial cells and an in vivo assessment of biocompatibility in rats. Microfibers of PCL containing totally encapsulated mesoporous silicon (pSi) particles at two different concentrations (6 and 20 wt%) were fabricated as non-woven fabrics. Given the dependence of Si particle dissolution kinetics on pSi surface chemistry, two different types of pSi particles (hydride terminated and surface oxidized) were evaluated for each of the two particle concentrations. Significant attachment of a human lens epithelial cell line (SRA 01/04) to all four types of scaffolds within a 24 hour period was observed. Implantation of silicon fabric samples beneath the conjunctiva of rat eyes for 8 weeks demonstrates that the composite materials did not cause visible infection or inflamm! ation, and do not erode the ocular surface. We suggest that these novel composite materials hold considerable promise as scaffolds in tissue engineering with controlled factor released properties.

PMID: 20350620 [PubMed - as supplied by publisher]

 

beta-Tricalcium phosphate promotes cell proliferation, osteogenesis and bone regeneration in intrabony defects in dogs.
March 31, 2010 at 6:37 AM

Related Articles

beta-Tricalcium phosphate promotes cell proliferation, osteogenesis and bone regeneration in intrabony defects in dogs.

Arch Oral Biol. 2009 Dec;54(12):1083-90

Authors: Neamat A, Gawish A, Gamal-Eldeen AM

OBJECTIVE: This study investigates the effect of the new synthetic bone grafting material, high pure-phase beta-tricalcium phosphate (Cerasorb(1) M, granule size 500-1000microm), on the osteogenesis process and proliferation marker in bone marrow stromal cells (BMSCs) and its regenerative effect in the periodontal intrabony defects in dogs. DESIGN: The effect of Cerasorb(1) M (20 and 40mgml(-1) for 1 and 2 weeks) on the proliferation rate of BMSCs was assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay on the proliferating cell nuclear antigen (PCNA) by immunoblotting and on alkaline phosphatase level by colourimetric assay. The regenerative effect of Cerasorb(1) M in the periodontal intrabony defects in dogs was investigated by histological and immunohistochemical analysis after 3 and 6 months of grafting. RESULTS: Incubation of BMSCs with Cerasorb(1) M for 2 weeks led to significant increase in cell proliferation rate, which ! was associated with increased PCNA. Cerasorb(1) M significantly increased the production of alkaline phosphatase as a marker for the osteogenic stromal lineage and for differentiation and bone formation in BMSCs after 2 weeks. In the histological features and immunohistochemical analysis of PCNA of the intrabony defects in dogs augmented with Cerasorb(1) M, osteoid tissue with a plate-like structure and cellular mesenchymal proliferation besides osteoid islands joined by bridges were observed after 3 months. Six months after the implantation, the Cerasorb(1) M granules were replaced by abundant new plate-like bone besides PCNA-enriched, small, oval-shaped mononuclear cells and multinucleated-giant cells that were attached to newly formed bones. No remains of the Cerasorb(1) M granules could be seen after 3 and 6 months with the newly formed plate-like bones and no histological sign of inflammatory reaction or formation of foreign-body granulomas. CONCLUSION: Cerasorb(1) M m! ay induce cell proliferation via induction of PCNA that may in! duce ear ly osteogenesis and bone formation. Cerasorb(1) M regenerated the bone completely in intrabony defects and that this regeneration was highly associated with PCNA expression in different cell lineage.

PMID: 19828137 [PubMed - indexed for MEDLINE]

 

Stem Cell Therapeutics Corp. Announces Completion of Enrollment in Key Modified REGENESIS Phase IIb Stroke Trial
March 31, 2010 at 6:34 AM

 

Structural Fat Grafting for Rejuvenation of the Dorsum of the Hand.
March 31, 2010 at 6:22 AM

Structural Fat Grafting for Rejuvenation of the Dorsum of the Hand.

Handchir Mikrochir Plast Chir. 2010 Apr;42(2):143-147

Authors: Giunta RE, Eder M, Machens HG, Müller DF, Kovacs L

In parallel with aging, increasing skin laxity and subcutaneous atrophy occur in many regions of the human body. Apart from the most obvious facial region, where most aesthetic operations for rejuvenation are done, also the dorsum of the hand is continuously visible in daily life. This region exhibits skin laxity, subcutaneous atrophy and age-related pigmentations in a comparable manner to the face. Autologous transplantation of fatty tissue (structural fat grafting, lipofilling) enables subcutaneous regeneration by refilling the subcutaneous space and hence reducing some of the age-related degenerative process. This paper illustrates the special operative technique on the hand in the form of a case report. Furthermore, 3D surface laser scanning permits an objective evaluation of the permanent volume effect over time. In the presented case a volume effect of 69% of the injected volume was measured after 6 months follow-up time. This amount of injected tissue seems! to be integrated as a graft and results in a reduction of subcutaneous atrophy in terms of a true regeneration. Structural fat grafting of the dorsum of the hand is thus a method of regenerative medicine. Together with other methods which reduce the age-related pigmentations, it plays a key role in our treatment concept for rejuvenation of the hand.

PMID: 20352578 [PubMed - as supplied by publisher]

 

Attenuation of Forkhead signaling by the retinal determination factor DACH1.
March 31, 2010 at 6:22 AM

Attenuation of Forkhead signaling by the retinal determination factor DACH1.

Proc Natl Acad Sci U S A. 2010 Mar 29;

Authors: Zhou J, Wang C, Wang Z, Dampier W, Wu K, Casimiro MC, Chepelev I, Popov VM, Quong A, Tozeren A, Zhao K, Lisanti MP, Pestell RG

The Drosophila Dachshund (Dac) gene, cloned as a dominant inhibitor of the hyperactive growth factor mutant ellipse, encodes a key component of the retinal determination gene network that governs cell fate. Herein, cyclic amplification and selection of targets identified a DACH1 DNA-binding sequence that resembles the FOX (Forkhead box-containing protein) binding site. Genome-wide in silico promoter analysis of DACH1 binding sites identified gene clusters populating cellular pathways associated with the cell cycle and growth factor signaling. ChIP coupled with high-throughput sequencing mapped DACH1 binding sites to corresponding gene clusters predicted in silico and identified as weight matrix resembling the cyclic amplification and selection of targets-defined sequence. DACH1 antagonized FOXM1 target gene expression, promoter occupancy in the context of local chromatin, and contact-independent growth. Attenuation of FOX function by the cell fate determination pa! thway has broad implications given the diverse role of FOX proteins in cellular biology and tumorigenesis.

PMID: 20351289 [PubMed - as supplied by publisher]

 

Experience With Robot Assisted Laparoscopic Surgery for Upper and Lower Benign and Malignant Ureteral Pathologies.
March 31, 2010 at 6:22 AM

Experience With Robot Assisted Laparoscopic Surgery for Upper and Lower Benign and Malignant Ureteral Pathologies.

Urology. 2010 Mar 27;

Authors: Hemal AK, Nayyar R, Gupta NP, Dorairajan LN

OBJECTIVES: To present our experience and outcomes of robot-assisted laparoscopic surgery (RALS) performed for different ureteral pathologies and to discuss the true utility of robotics in ureteral surgery. METHODS: We reviewed a total of 44 procedures performed for diverse ureteral pathologies involving the proximal and distal ureter in 2 institutions from July 2006 to July 2009. Operative time, blood loss, length of stay, complications, and subjective and objective follow-up were evaluated. RESULTS: The 44 cases included 18 distal ureteral procedures including 5 distal ureterectomy with ureteroneocystostomy; 1 ureteroneocystostomy with psoas hitch; 2 ureteroneocystostomy with vesicovaginal fistula repair; 9 megaureter repairs in 8 cases; there were 12 proximal ureteral procedures including 7 ureteroureterostomies and 4 retrocaval ureter repairs; 10 ablative procedures consisting of 5 nephroureterectomies with cuff of bladder and 5 nephroureterectomies and 4 misc! ellaneous procedures. The mean operative time was 137.9 minutes (range: 70-240). Mean blood loss was 98.2 mL (range: <50-400). There were no urine leaks. Mean drain tube duration was 1.4 days (range: 1-2.5) and mean hospital stay was 2.4 days (range: 1-6). Complications included 1 case of sepsis and 1 antibiotic-induced infection. Average follow-up period was 13.5 months. Operative success as defined by symptom resolution and imaging was 100%. CONCLUSIONS: RALS is feasible, safe, and an effective option for ureteral pathologies at any level of the ureter with minimal peri-operative morbidity. However, appropriate port placement, patient positioning, and versatile experience of team is critical in handling such cases for better outcomes.

PMID: 20350753 [PubMed - as supplied by publisher]

 

The potential of mesenchymal stem cells for neural repair.
March 31, 2010 at 6:22 AM

The potential of mesenchymal stem cells for neural repair.

Discov Med. 2010 Mar;9(46):236-42

Authors: Miller RH, Bai L, Lennon DP, Caplan AI

Developing effective therapies for serious neurological insults remains a major challenge for biomedical research. Despite intense efforts, the ability to promote functional recovery after contusion injuries, ischemic insults, or the onset of neurodegenerative diseases in the brain and spinal cord remains very limited even while the need for such therapies is increasing with an aging population. Recent studies suggest that cellular therapies utilizing mesenchymal stem cells (MSCs) may provide a functional benefit in a wide range of neurological insults. MSCs derived from a variety of tissue sources have been therapeutically evaluated in animal models of stroke, spinal cord injury, and multiple sclerosis. In each situation, treatment with MSCs results in substantial functional benefit and these pre-clinical studies have led to the initiation of a number of clinical trials worldwide in neural repair.

PMID: 20350491 [PubMed - in process]

 

Genetically modified mesenchymal stem cells and their clinical potential in acute cardiovascular disease.
March 31, 2010 at 6:22 AM

Genetically modified mesenchymal stem cells and their clinical potential in acute cardiovascular disease.

Discov Med. 2010 Mar;9(46):219-23

Authors: Griffin M, Greiser U, Barry F, O'Brien T, Ritter T

Adult mesenchymal stem cells (MSCs) are non-hematopoietic cells with multi-lineage potential to differentiate into various tissues of mesodermal origin. They can be isolated from bone marrow and other tissues and have the capacity to extensively proliferate in vitro. Moreover, MSCs have also been shown to produce anti-inflammatory molecules which can modulate humoral and cellular immune responses. Considering their regenerative potential and immunoregulatory effect, MSC therapy is a promising tool in the treatment of degenerative, inflammatory, and autoimmune diseases. However, the current understanding from results of clinical trials is that MSC-therapy is safe but its therapeutic efficiency needs to be improved. In this article we will focus on options for genetic manipulation of MSCs and on current progress in adapting genetically-modified MSCs for clinical use in acute cardiovascular disease.

PMID: 20350488 [PubMed - in process]

 

Egg-citing advances in generating primordial germ cells in the laboratory.
March 31, 2010 at 6:22 AM

Related Articles

Egg-citing advances in generating primordial germ cells in the laboratory.

Biol Reprod. 2010 Feb;82(2):233-4

Authors: Clark AT

PMID: 20018911 [PubMed - indexed for MEDLINE]

 

The presence and activation of two essential transcription factors (cAMP response element-binding protein and cAMP-dependent transcription factor ATF1) in the two-cell mouse embryo.
March 31, 2010 at 6:22 AM

Related Articles

The presence and activation of two essential transcription factors (cAMP response element-binding protein and cAMP-dependent transcription factor ATF1) in the two-cell mouse embryo.

Biol Reprod. 2010 Feb;82(2):459-68

Authors: Jin XL, O'Neill C

The expression of two members of an important family of transcription factors, cAMP response element-binding protein (CREB) and cAMP-dependent transcription factor ATF1 (ATF1), is essential for normal preimplantation development. There is a high degree of functional similarity between these two transcription factors, and they can both homodimerize and heterodimerize with each other to form active transcription factors. CREB is present in all stages of mouse preimplantation embryo, and we show here that ATF1 is localized to the nucleus in all preimplantation stages. Activation of these transcription factors requires their phosphorylation, and this was only observed to occur for both transcription factors (serine 133 phosphorylation of CREB and serine 63 phosphorylation of ATF1) at the two-cell stage. Nuclear localization and phosphorylation of ATF1 were constitutive. The nuclear localization and phosphorylation of CREB showed a constitutive component that was furth! er induced by the autocrine embryotropin Paf (1-o-alkyl-2-acetyl-sn-glycero-3-phosphocholine). Activation of CREB by Paf was independent of cAMP but was dependent on calcium, calmodulin, and calmodulin-dependent kinase activity. ATF1 nuclear localization was unaffected by inhibition of the calcium/calmodulin pathway. A complex pattern of expression of calmodulin-dependent kinases was observed throughout preimplantation development. At the two-cell stage, only mRNAs coding for calmodulin-dependent protein kinase kinase beta, calmodulin-dependent protein kinase II gamma, and calmodulin-dependent protein kinase IV were detected. A selective antagonist for calmodulin-dependent protein kinase kinase (STO-609) and calmodulin-dependent protein kinases I, II, and IV (KN-62) blocked the Paf-induced phosphorylation of CREB. The study demonstrates a role for trophic signaling and constitutive activation of two essential transcription factors at the time of zygotic genome activation.

PMID: 19776387 [PubMed - indexed for MEDLINE]

 

NFIX--one gene, two knockouts, multiple effects.
March 31, 2010 at 6:22 AM

Related Articles

NFIX--one gene, two knockouts, multiple effects.

J Biol. 2008;7(8):29

Authors: Pekarik V, Belmonte JC

A previous knockout of the transcription factor gene nuclear factor IX (NFIX) in mice produced impaired development of the corpus callosum and severe skeletal defects. A recent paper in BMC Developmental Biology reports an apparently similar NFIX knockout that produced marked differences in phenotype, raising intriguing general questions about the possible causes of such differences in mouse knockouts.

PMID: 18983696 [PubMed - indexed for MEDLINE]

 

Endoplasmic Reticulum Stress Signals in Defined Human Embryonic Stem Cell Lines and Culture Conditions.
March 31, 2010 at 6:21 AM

Endoplasmic Reticulum Stress Signals in Defined Human Embryonic Stem Cell Lines and Culture Conditions.

Stem Cell Rev. 2010 Mar 30;

Authors: Blanco-Gelaz MA, Suarez-Alvarez B, Ligero G, Sanchez L, Vidal-Castiñeira JR, Coto E, Moore H, Menendez P, Lopez-Larrea C

Human embryonic stem cells (hESCs) are especially resistant to several cellular stresses, but the existence and induction of Endoplasmic Reticulum (ER) stress by culture conditions are unknown. Using qPCR, here, we investigated the behavior of the principal sensors of ER stress and their relation with the feeder layer, the type of conditioned media used in feeder free systems and the upregulation of several differentiation markers. We observed the preservation of pluripotency, and detected differential expression of differentiation markers in HS181 and SHEF1 hESCs growing on Adipose-derived mesenchymal stem cells (ASCs) and feeder-free system with different conditioned media (HEF-CM and ASC-CM). Taken together, these results demonstrate evidence of ER stress events that cells must resolve to survive and maintenance of markers of pluripotency. The early differentiation status defined could progress into a more differentiated state, and may be influenced by culture ! conditions.

PMID: 20352530 [PubMed - as supplied by publisher]

 

Effects of Adipose Tissue-Derived Stem Cell Therapy After Myocardial Infarction: Impact of the Route of Administration.
March 31, 2010 at 6:21 AM

Effects of Adipose Tissue-Derived Stem Cell Therapy After Myocardial Infarction: Impact of the Route of Administration.

J Card Fail. 2010 Apr;16(4):357-366

Authors: Rigol M, Solanes N, Farré J, Roura S, Roqué M, Berruezo A, Bellera N, Novensà L, Tamborero D, Prat-Vidal C, Huzman MA, Batlle M, Hoefsloot M, Sitges M, Ramírez J, Dantas AP, Merino A, Sanz G, Brugada J, Bayés-Genís A, Heras M

BACKGROUND: Cell-based therapies offer a promising approach to reducing the short-term mortality rate associated with heart failure after a myocardial infarction. The aim of the study was to analyze histological and functional effects of adipose tissue-derived stem cells (ADSCs) after myocardial infarction and compare 2 types of administration pathways. METHODS AND RESULTS: ADSCs from 28 pigs were labeled by transfection. Animals that survived myocardial infarction (n = 19) received: intracoronary culture media (n = 4); intracoronary ADSCs (n = 5); transendocardial culture media (n = 4); or transendocardial ADSCs (n = 6). At 3 weeks' follow-up, intracoronary and transendocardial administration of ADSCs resulted in similar rates of engrafted cells (0.85 [0.19-1.97] versus 2 [1-2] labeled cells/cm(2), respectively; P = NS) and some of those cells expressed smooth muscle cell markers. The intracoronary administration of ADSCs was more effective in increasing the ! number of small vessels than transendocardial administration (223 +/- 40 versus 168 +/- 35 vessels/mm(2); P < .05). Ejection fraction was not modified by stem cell therapy. CONCLUSIONS: This is the first study to compare intracoronary and transendocardial administration of autologous ADSCs in a porcine model of myocardial infarction. Both pathways of ADSCs delivery are feasible, producing a similar number of engrafted and differentiated cells, although intracoronary administration was more effective in increasing neovascularization.

PMID: 20350704 [PubMed - as supplied by publisher]

 

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4/1 pubmed: adipose stem cell

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Endoplasmic Reticulum Stress Signals in Defined Human Embryonic Stem Cell Lines and Culture Conditions.
March 31, 2010 at 6:21 AM

Endoplasmic Reticulum Stress Signals in Defined Human Embryonic Stem Cell Lines and Culture Conditions.

Stem Cell Rev. 2010 Mar 30;

Authors: Blanco-Gelaz MA, Suarez-Alvarez B, Ligero G, Sanchez L, Vidal-Castiñeira JR, Coto E, Moore H, Menendez P, Lopez-Larrea C

Human embryonic stem cells (hESCs) are especially resistant to several cellular stresses, but the existence and induction of Endoplasmic Reticulum (ER) stress by culture conditions are unknown. Using qPCR, here, we investigated the behavior of the principal sensors of ER stress and their relation with the feeder layer, the type of conditioned media used in feeder free systems and the upregulation of several differentiation markers. We observed the preservation of pluripotency, and detected differential expression of differentiation markers in HS181 and SHEF1 hESCs growing on Adipose-derived mesenchymal stem cells (ASCs) and feeder-free system with different conditioned media (HEF-CM and ASC-CM). Taken together, these results demonstrate evidence of ER stress events that cells must resolve to survive and maintenance of markers of pluripotency. The early differentiation status defined could progress into a more differentiated state, and may be influenced by culture ! conditions.

PMID: 20352530 [PubMed - as supplied by publisher]

 

Effects of Adipose Tissue-Derived Stem Cell Therapy After Myocardial Infarction: Impact of the Route of Administration.
March 31, 2010 at 6:21 AM

Effects of Adipose Tissue-Derived Stem Cell Therapy After Myocardial Infarction: Impact of the Route of Administration.

J Card Fail. 2010 Apr;16(4):357-366

Authors: Rigol M, Solanes N, Farré J, Roura S, Roqué M, Berruezo A, Bellera N, Novensà L, Tamborero D, Prat-Vidal C, Huzman MA, Batlle M, Hoefsloot M, Sitges M, Ramírez J, Dantas AP, Merino A, Sanz G, Brugada J, Bayés-Genís A, Heras M

BACKGROUND: Cell-based therapies offer a promising approach to reducing the short-term mortality rate associated with heart failure after a myocardial infarction. The aim of the study was to analyze histological and functional effects of adipose tissue-derived stem cells (ADSCs) after myocardial infarction and compare 2 types of administration pathways. METHODS AND RESULTS: ADSCs from 28 pigs were labeled by transfection. Animals that survived myocardial infarction (n = 19) received: intracoronary culture media (n = 4); intracoronary ADSCs (n = 5); transendocardial culture media (n = 4); or transendocardial ADSCs (n = 6). At 3 weeks' follow-up, intracoronary and transendocardial administration of ADSCs resulted in similar rates of engrafted cells (0.85 [0.19-1.97] versus 2 [1-2] labeled cells/cm(2), respectively; P = NS) and some of those cells expressed smooth muscle cell markers. The intracoronary administration of ADSCs was more effective in increasing the numb! er of small vessels than transendocardial administration (223 +/- 40 versus 168 +/- 35 vessels/mm(2); P < .05). Ejection fraction was not modified by stem cell therapy. CONCLUSIONS: This is the first study to compare intracoronary and transendocardial administration of autologous ADSCs in a porcine model of myocardial infarction. Both pathways of ADSCs delivery are feasible, producing a similar number of engrafted and differentiated cells, although intracoronary administration was more effective in increasing neovascularization.

PMID: 20350704 [PubMed - as supplied by publisher]

 

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4/1 RegenMD

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NFIX--one gene, two knockouts, multiple effects.
March 31, 2010 at 8:17 AM

Related Articles

NFIX--one gene, two knockouts, multiple effects.

J Biol. 2008;7(8):29

Authors: Pekarik V, Belmonte JC

A previous knockout of the transcription factor gene nuclear fac! tor IX (NFIX) in mice produced impaired development of the corpus callosum and severe skeletal defects. A recent paper in BMC Developmental Biology reports an apparently similar NFIX knockout that produced marked differences in phenotype, raising intriguing general questions about the possible causes of such differences in mouse knockouts.

PMID: 18983696 [PubMed - indexed for MEDLINE]

 

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This email was carefully delivered by Feed My Inbox. 230 Franklin Road Suite 814 Franklin, TN 37064

4/1 pubmed: "regenerative medici...

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Structural Fat Grafting for Rejuvenation of the Dorsum of the Hand.
March 31, 2010 at 7:06 AM

Structural Fat Grafting for Rejuvenation of the Dorsum of the Hand.

Handchir Mikrochir Plast Chir. 2010 Apr;42(2):143-147

Authors: Giunta RE, Eder M, Machens HG, Müller DF, Kovacs L

In parallel with aging, increasing skin laxity and subcutaneous atrophy occur in many regions of the human body. Apart from the most obvious facial region, where most aesthetic operations for rejuvenation are done, also the dorsum of the hand is continuously visible in daily life. This region exhibits skin laxity, subcutaneous atrophy and age-related pigmentations in a comparable manner to the face. Autologous transplantation of fatty tissue (structural fat grafting, lipofilling) enables subcutaneous regeneration by refilling the subcutaneous space and hence reducing some of the age-related degenerative process. This paper illustrates the special operative technique on the hand in the form of a case report. Furthermore, 3D surface laser scanning permits an objective evaluation of the permanent volume effect over time. In the presented case a volume effect of 69% of the injected volume was measured after 6 months follow-up time. This amount of injected tissue seems! to be integrated as a graft and results in a reduction of subcutaneous atrophy in terms of a true regeneration. Structural fat grafting of the dorsum of the hand is thus a method of regenerative medicine. Together with other methods which reduce the age-related pigmentations, it plays a key role in our treatment concept for rejuvenation of the hand.

PMID: 20352578 [PubMed - as supplied by publisher]

 

Adipose Stem Cells for Soft Tissue Regeneration.
March 31, 2010 at 7:06 AM

Adipose Stem Cells for Soft Tissue Regeneration.

Handchir Mikrochir Plast Chir. 2010 Apr;42(2):124-128

Authors: Brayfield C, Marra K, Rubin JP

Adipose-derived stem cells (ASCs) can be isolated from human adipose tissue with the exceptional potential for differentiation into mature adipocytes. Utilization of this system is very promising in developing improved techniques to repair soft tissue defects. Current reconstructive procedures, especially after trauma and oncological surgery, transfer autologous soft tissue grafts having limitations. However, ASCs offer the ability to either generate soft tissue with no donor-site morbidity (with the exception of a minor loss of adipose tissue) or enhance the viability and durability of other grafts. This review will discuss the relevant properties of human adult adipose-derived stem cells for the regeneration of adipose tissue. Discussion will focus on the biology of ASCs, cell delivery vehicles/scaffolds useful in applying ASCs as a therapy, and suitable IN VIVO animal models for studying adipose tissue engineering. Also included is a description of the current ! clinical studies with ASCs in Europe and Asia.

PMID: 20352575 [PubMed - as supplied by publisher]

 

Stem cells for myocardial repair.
March 31, 2010 at 7:06 AM

Stem cells for myocardial repair.

Thromb Haemost. 2010 Mar 29;104(1)

Authors: Siu CW, Liao SY, Liu Y, Lian Q, Tse HF

There is a growing interest in the clinical application for stem cell as a novel therapy for treatment of acute myocardial infarction and chronic myocardial ischaemia. The initial premise is the transplanted exogenous stem cells can engraft and integrate with host myocardium for cardiac regeneration. However, recent experimental studies suggest that multiple mechanisms, including remodelling of extracellular matrix, enhancement of neovascularisation and recruitment of endogenous stem cells are more likely to contribute to the beneficial effects of stem cell therapy that direct trans-differentiation of stem cells into functional myocardium. Among different potential cell sources, bone marrow-derived cells and skeletal myoblasts have been tested in pilot clinical trials. Phase I/II randomised controlled clinical trials suggest that intracoronary or intramyocardial injection of bone marrow-derived cells may be safe and feasible strategies for treatment of acute myoca! rdial infarction as well as chronic myocardial ischaemia. In addition, these studies show a modest, but significant improvement in left ventricular ejection fraction and clinical status of patients after cell transplantation. Nevertheless, most of these studies included a relatively small sample size (<200) and short duration of follow-up (<6 months), and the clinical efficacy of stem cell therapy need to be confirmed by future clinical trials. Furthermore, the optimal timing, cell types and mode of delivery need to be addressed, and strategies to improve cell survival and engraftment should also be developed to overcome the potential hurdles related to cell-based therapy.

PMID: 20352151 [PubMed - as supplied by publisher]

 

Attenuation of Forkhead signaling by the retinal determination factor DACH1.
March 31, 2010 at 7:06 AM

Attenuation of Forkhead signaling by the retinal determination factor DACH1.

Proc Natl Acad Sci U S A. 2010 Mar 29;

Authors: Zhou J, Wang C, Wang Z, Dampier W, Wu K, Casimiro MC, Chepelev I, Popov VM, Quong A, Tozeren A, Zhao K, Lisanti MP, Pestell RG

The Drosophila Dachshund (Dac) gene, cloned as a dominant inhibitor of the hyperactive growth factor mutant ellipse, encodes a key component of the retinal determination gene network that governs cell fate. Herein, cyclic amplification and selection of targets identified a DACH1 DNA-binding sequence that resembles the FOX (Forkhead box-containing protein) binding site. Genome-wide in silico promoter analysis of DACH1 binding sites identified gene clusters populating cellular pathways associated with the cell cycle and growth factor signaling. ChIP coupled with high-throughput sequencing mapped DACH1 binding sites to corresponding gene clusters predicted in silico and identified as weight matrix resembling the cyclic amplification and selection of targets-defined sequence. DACH1 antagonized FOXM1 target gene expression, promoter occupancy in the context of local chromatin, and contact-independent growth. Attenuation of FOX function by the cell fate determination pa! thway has broad implications given the diverse role of FOX proteins in cellular biology and tumorigenesis.

PMID: 20351289 [PubMed - as supplied by publisher]

 

Experience With Robot Assisted Laparoscopic Surgery for Upper and Lower Benign and Malignant Ureteral Pathologies.
March 31, 2010 at 7:06 AM

Experience With Robot Assisted Laparoscopic Surgery for Upper and Lower Benign and Malignant Ureteral Pathologies.

Urology. 2010 Mar 27;

Authors: Hemal AK, Nayyar R, Gupta NP, Dorairajan LN

OBJECTIVES: To present our experience and outcomes of robot-assisted laparoscopic surgery (RALS) performed for different ureteral pathologies and to discuss the true utility of robotics in ureteral surgery. METHODS: We reviewed a total of 44 procedures performed for diverse ureteral pathologies involving the proximal and distal ureter in 2 institutions from July 2006 to July 2009. Operative time, blood loss, length of stay, complications, and subjective and objective follow-up were evaluated. RESULTS: The 44 cases included 18 distal ureteral procedures including 5 distal ureterectomy with ureteroneocystostomy; 1 ureteroneocystostomy with psoas hitch; 2 ureteroneocystostomy with vesicovaginal fistula repair; 9 megaureter repairs in 8 cases; there were 12 proximal ureteral procedures including 7 ureteroureterostomies and 4 retrocaval ureter repairs; 10 ablative procedures consisting of 5 nephroureterectomies with cuff of bladder and 5 nephroureterectomies and 4 misc! ellaneous procedures. The mean operative time was 137.9 minutes (range: 70-240). Mean blood loss was 98.2 mL (range: <50-400). There were no urine leaks. Mean drain tube duration was 1.4 days (range: 1-2.5) and mean hospital stay was 2.4 days (range: 1-6). Complications included 1 case of sepsis and 1 antibiotic-induced infection. Average follow-up period was 13.5 months. Operative success as defined by symptom resolution and imaging was 100%. CONCLUSIONS: RALS is feasible, safe, and an effective option for ureteral pathologies at any level of the ureter with minimal peri-operative morbidity. However, appropriate port placement, patient positioning, and versatile experience of team is critical in handling such cases for better outcomes.

PMID: 20350753 [PubMed - as supplied by publisher]

 

Effects of Adipose Tissue-Derived Stem Cell Therapy After Myocardial Infarction: Impact of the Route of Administration.
March 31, 2010 at 7:06 AM

Effects of Adipose Tissue-Derived Stem Cell Therapy After Myocardial Infarction: Impact of the Route of Administration.

J Card Fail. 2010 Apr;16(4):357-366

Authors: Rigol M, Solanes N, Farré J, Roura S, Roqué M, Berruezo A, Bellera N, Novensà L, Tamborero D, Prat-Vidal C, Huzman MA, Batlle M, Hoefsloot M, Sitges M, Ramírez J, Dantas AP, Merino A, Sanz G, Brugada J, Bayés-Genís A, Heras M

BACKGROUND: Cell-based therapies offer a promising approach to reducing the short-term mortality rate associated with heart failure after a myocardial infarction. The aim of the study was to analyze histological and functional effects of adipose tissue-derived stem cells (ADSCs) after myocardial infarction and compare 2 types of administration pathways. METHODS AND RESULTS: ADSCs from 28 pigs were labeled by transfection. Animals that survived myocardial infarction (n = 19) received: intracoronary culture media (n = 4); intracoronary ADSCs (n = 5); transendocardial culture media (n = 4); or transendocardial ADSCs (n = 6). At 3 weeks' follow-up, intracoronary and transendocardial administration of ADSCs resulted in similar rates of engrafted cells (0.85 [0.19-1.97] versus 2 [1-2] labeled cells/cm(2), respectively; P = NS) and some of those cells expressed smooth muscle cell markers. The intracoronary administration of ADSCs was more effective in increasing the numb! er of small vessels than transendocardial administration (223 +/- 40 versus 168 +/- 35 vessels/mm(2); P < .05). Ejection fraction was not modified by stem cell therapy. CONCLUSIONS: This is the first study to compare intracoronary and transendocardial administration of autologous ADSCs in a porcine model of myocardial infarction. Both pathways of ADSCs delivery are feasible, producing a similar number of engrafted and differentiated cells, although intracoronary administration was more effective in increasing neovascularization.

PMID: 20350704 [PubMed - as supplied by publisher]

 

Tailoring the morphology of high molecular weight PLLA scaffolds through bioglass additions.
March 31, 2010 at 7:06 AM

Tailoring the morphology of high molecular weight PLLA scaffolds through bioglass additions.

Acta Biomater. 2010 Mar 26;

Authors: Barroca N, Daniel-da-Silva AL, Vilarinho PM, Fernandes MH

Thermally induced phase separation (TIPS) has been used in the last years to prepare porous structures for tissue engineering applications and particular attention has been paid to the increase of pore size without the use of possible toxic surfactants. Within this context, an alternative method to control the porosity of polymeric scaffolds via the combination with a bioglass is proposed in this work. By the addition of a bioactive glass from the 3CaO.P(2)O(5)-MgO-SiO(2) system, the porous structure of high molecular weight poly (L-lactic) acid (PLLA) scaffolds prepared by TIPS is tailored. Bioglass acts as a nucleating catalyst agent of the PLLA matrix promoting its crystallization and the glass solubility controls the pore size. A significant increase of the pore size is observed as the BG content increases and scaffolds with large pore size (ca. 150mum) can be prepared. In addition, the bioactive character of the scaffolds is proved by in vitro tests in synthe! tic plasma. The importance of this approach resides on the combination of the ability to tailor the porosity of polymeric scaffolds via the tunable solubility of bioglasses, without the use of toxic surfactants, leading to a composite structure with suitable properties for bone tissue engineering applications.

PMID: 20350622 [PubMed - as supplied by publisher]

 

Evaluation of Mesoporous Silicon / Polycaprolactone Composites as Ophthalmic Implants.
March 31, 2010 at 7:06 AM

Evaluation of Mesoporous Silicon / Polycaprolactone Composites as Ophthalmic Implants.

Acta Biomater. 2010 Mar 26;

Authors: Kashanian S, Harding F, Irani Y, Klebe S, Marshall K, Loni A, Canham L, Fan D, Williams KA, Voelcker NH, Coffer JL

The suitability of mesoporous silicon encapsulated in microfibers of the biodegradable polymer polycaprolactone (PCL) for ophthalmic applications was evaluated, using both a cell attachment assay with epithelial cells and an in vivo assessment of biocompatibility in rats. Microfibers of PCL containing totally encapsulated mesoporous silicon (pSi) particles at two different concentrations (6 and 20 wt%) were fabricated as non-woven fabrics. Given the dependence of Si particle dissolution kinetics on pSi surface chemistry, two different types of pSi particles (hydride terminated and surface oxidized) were evaluated for each of the two particle concentrations. Significant attachment of a human lens epithelial cell line (SRA 01/04) to all four types of scaffolds within a 24 hour period was observed. Implantation of silicon fabric samples beneath the conjunctiva of rat eyes for 8 weeks demonstrates that the composite materials did not cause visible infection or inflamm! ation, and do not erode the ocular surface. We suggest that these novel composite materials hold considerable promise as scaffolds in tissue engineering with controlled factor released properties.

PMID: 20350620 [PubMed - as supplied by publisher]

 

The potential of mesenchymal stem cells for neural repair.
March 31, 2010 at 7:06 AM

The potential of mesenchymal stem cells for neural repair.

Discov Med. 2010 Mar;9(46):236-42

Authors: Miller RH, Bai L, Lennon DP, Caplan AI

Developing effective therapies for serious neurological insults remains a major challenge for biomedical research. Despite intense efforts, the ability to promote functional recovery after contusion injuries, ischemic insults, or the onset of neurodegenerative diseases in the brain and spinal cord remains very limited even while the need for such therapies is increasing with an aging population. Recent studies suggest that cellular therapies utilizing mesenchymal stem cells (MSCs) may provide a functional benefit in a wide range of neurological insults. MSCs derived from a variety of tissue sources have been therapeutically evaluated in animal models of stroke, spinal cord injury, and multiple sclerosis. In each situation, treatment with MSCs results in substantial functional benefit and these pre-clinical studies have led to the initiation of a number of clinical trials worldwide in neural repair.

PMID: 20350491 [PubMed - in process]

 

Genetically modified mesenchymal stem cells and their clinical potential in acute cardiovascular disease.
March 31, 2010 at 7:06 AM

Genetically modified mesenchymal stem cells and their clinical potential in acute cardiovascular disease.

Discov Med. 2010 Mar;9(46):219-23

Authors: Griffin M, Greiser U, Barry F, O'Brien T, Ritter T

Adult mesenchymal stem cells (MSCs) are non-hematopoietic cells with multi-lineage potential to differentiate into various tissues of mesodermal origin. They can be isolated from bone marrow and other tissues and have the capacity to extensively proliferate in vitro. Moreover, MSCs have also been shown to produce anti-inflammatory molecules which can modulate humoral and cellular immune responses. Considering their regenerative potential and immunoregulatory effect, MSC therapy is a promising tool in the treatment of degenerative, inflammatory, and autoimmune diseases. However, the current understanding from results of clinical trials is that MSC-therapy is safe but its therapeutic efficiency needs to be improved. In this article we will focus on options for genetic manipulation of MSCs and on current progress in adapting genetically-modified MSCs for clinical use in acute cardiovascular disease.

PMID: 20350488 [PubMed - in process]

 

Egg-citing advances in generating primordial germ cells in the laboratory.
March 31, 2010 at 7:06 AM

Related Articles

Egg-citing advances in generating primordial germ cells in the laboratory.

Biol Reprod. 2010 Feb;82(2):233-4

Authors: Clark AT

PMID: 20018911 [PubMed - indexed for MEDLINE]

 

beta-Tricalcium phosphate promotes cell proliferation, osteogenesis and bone regeneration in intrabony defects in dogs.
March 31, 2010 at 7:06 AM

Related Articles

beta-Tricalcium phosphate promotes cell proliferation, osteogenesis and bone regeneration in intrabony defects in dogs.

Arch Oral Biol. 2009 Dec;54(12):1083-90

Authors: Neamat A, Gawish A, Gamal-Eldeen AM

OBJECTIVE: This study investigates the effect of the new synthetic bone grafting material, high pure-phase beta-tricalcium phosphate (Cerasorb(1) M, granule size 500-1000microm), on the osteogenesis process and proliferation marker in bone marrow stromal cells (BMSCs) and its regenerative effect in the periodontal intrabony defects in dogs. DESIGN: The effect of Cerasorb(1) M (20 and 40mgml(-1) for 1 and 2 weeks) on the proliferation rate of BMSCs was assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay on the proliferating cell nuclear antigen (PCNA) by immunoblotting and on alkaline phosphatase level by colourimetric assay. The regenerative effect of Cerasorb(1) M in the periodontal intrabony defects in dogs was investigated by histological and immunohistochemical analysis after 3 and 6 months of grafting. RESULTS: Incubation of BMSCs with Cerasorb(1) M for 2 weeks led to significant increase in cell proliferation rate, which ! was associated with increased PCNA. Cerasorb(1) M significantly increased the production of alkaline phosphatase as a marker for the osteogenic stromal lineage and for differentiation and bone formation in BMSCs after 2 weeks. In the histological features and immunohistochemical analysis of PCNA of the intrabony defects in dogs augmented with Cerasorb(1) M, osteoid tissue with a plate-like structure and cellular mesenchymal proliferation besides osteoid islands joined by bridges were observed after 3 months. Six months after the implantation, the Cerasorb(1) M granules were replaced by abundant new plate-like bone besides PCNA-enriched, small, oval-shaped mononuclear cells and multinucleated-giant cells that were attached to newly formed bones. No remains of the Cerasorb(1) M granules could be seen after 3 and 6 months with the newly formed plate-like bones and no histological sign of inflammatory reaction or formation of foreign-body granulomas. CONCLUSION: Cerasorb(1) M m! ay induce cell proliferation via induction of PCNA that may in! duce ear ly osteogenesis and bone formation. Cerasorb(1) M regenerated the bone completely in intrabony defects and that this regeneration was highly associated with PCNA expression in different cell lineage.

PMID: 19828137 [PubMed - indexed for MEDLINE]

 

The presence and activation of two essential transcription factors (cAMP response element-binding protein and cAMP-dependent transcription factor ATF1) in the two-cell mouse embryo.
March 31, 2010 at 7:06 AM

Related Articles

The presence and activation of two essential transcription factors (cAMP response element-binding protein and cAMP-dependent transcription factor ATF1) in the two-cell mouse embryo.

Biol Reprod. 2010 Feb;82(2):459-68

Authors: Jin XL, O'Neill C

The expression of two members of an important family of transcription factors, cAMP response element-binding protein (CREB) and cAMP-dependent transcription factor ATF1 (ATF1), is essential for normal preimplantation development. There is a high degree of functional similarity between these two transcription factors, and they can both homodimerize and heterodimerize with each other to form active transcription factors. CREB is present in all stages of mouse preimplantation embryo, and we show here that ATF1 is localized to the nucleus in all preimplantation stages. Activation of these transcription factors requires their phosphorylation, and this was only observed to occur for both transcription factors (serine 133 phosphorylation of CREB and serine 63 phosphorylation of ATF1) at the two-cell stage. Nuclear localization and phosphorylation of ATF1 were constitutive. The nuclear localization and phosphorylation of CREB showed a constitutive component that was furth! er induced by the autocrine embryotropin Paf (1-o-alkyl-2-acetyl-sn-glycero-3-phosphocholine). Activation of CREB by Paf was independent of cAMP but was dependent on calcium, calmodulin, and calmodulin-dependent kinase activity. ATF1 nuclear localization was unaffected by inhibition of the calcium/calmodulin pathway. A complex pattern of expression of calmodulin-dependent kinases was observed throughout preimplantation development. At the two-cell stage, only mRNAs coding for calmodulin-dependent protein kinase kinase beta, calmodulin-dependent protein kinase II gamma, and calmodulin-dependent protein kinase IV were detected. A selective antagonist for calmodulin-dependent protein kinase kinase (STO-609) and calmodulin-dependent protein kinases I, II, and IV (KN-62) blocked the Paf-induced phosphorylation of CREB. The study demonstrates a role for trophic signaling and constitutive activation of two essential transcription factors at the time of zygotic genome activation.

PMID: 19776387 [PubMed - indexed for MEDLINE]

 

NFIX--one gene, two knockouts, multiple effects.
March 31, 2010 at 7:06 AM

Related Articles

NFIX--one gene, two knockouts, multiple effects.

J Biol. 2008;7(8):29

Authors: Pekarik V, Belmonte JC

A previous knockout of the transcription factor gene nuclear factor IX (NFIX) in mice produced impaired development of the corpus callosum and severe skeletal defects. A recent paper in BMC Developmental Biology reports an apparently similar NFIX knockout that produced marked differences in phenotype, raising intriguing general questions about the possible causes of such differences in mouse knockouts.

PMID: 18983696 [PubMed - indexed for MEDLINE]

 

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