Generation of Endoderm derived Human iPS cells from …
By JoanneRUSSELL25
Hepatology. Author manuscript; available in PMC 2011 May 1.
Published in final edited form as:
PMCID: PMC2925460
NIHMSID: NIHMS221023
Recent advances in induced pluripotent stem (iPS) cell research significantly changed our perspective on regenerative medicine. Patient specific iPS cells have been derived not only for disease modeling but also as sources for cell replacement therapy. However, there have been insufficient data to prove that iPS cells are functionally equivalent to hES cells or safer than hES cells. There are several important issues which need to be addressed and foremost are the safety and efficacy of human iPS cells from different origins. Human iPS cells have been derived mostly from cells originated from mesoderm, with a few cases from ectoderm. So far there has been no report of endoderm derived human iPS cells, preventing comprehensive comparative investigations on the quality of human iPS cells from different origins.
Here we show for the first time reprogramming of human endoderm derived cells (i.e. primary hepatocytes) to pluripotency. Hepatocyte-derived iPS cells appear indistinguishable from human embryonic stem cells in colony morphology, growth properties, expression of pluripotency-associated transcription factors and surface markers, and differentiation potential in embryoid body formation and teratoma assays. In addition, these cells were able to directly differentiate into definitive endoderm, hepatic progenitors, and mature hepatocytes. The technology to develop endoderm derived human iPS cell lines, together with other established cell lines, will provide a foundation to elucidate the mechanisms of cellular reprogramming and to study the safety and efficacy of differentially originated human iPS cells for cell therapy. For studying liver disease pathogenesis, this technology also provides a potentially more amenable system to generate liver disease specific iPS cells.
Recent advances in induced pluripotent stem (iPS) cell research have provided great potential for these somatic cell-derived stem cells as sources for cell replacement therapy and for establishing disease models.114 Human iPS cells have been shown to be pluripotent in in vitro differentiation and in vivo teratoma assays, similar to human embryonic stem (hES) cells.914 Disease-specific iPS cell lines have been generated from fibroblasts and blood cells and some of the disease features have been recapitulated in tissue culture after directed differentiation of the iPS cells, demonstrating the power of this technology in disease modeling.13,15 However, several key issues have to be addressed in order for the iPS cells to be used for clinical purposes. First, although pluripotency has been demonstrated, it is premature to claim that iPS cells are functionally equivalent to hES cells. In fact, one study has suggested that iPS cells have distinct protein-coding and microRNA gene expression signatures from ES cells.1 These differences can not be completely explained by the reactivation of transgenes used in the reprogramming process since human iPS cells generated without viral or transgene integration also displayed a different transcriptional signature compared to hES cells.2 Secondly it was demonstrated that human iPS cells retained certain gene expression of the parent cells, suggesting that iPS cells from different origins may possess different capacity to differentiate.2 This issue is important not only for the purposes of generating functional cell types for therapy but also for safety implications. A comprehensive study using various mouse iPS cells has demonstrated that the origin of the iPS cells had a profound influence on the tumor-forming propensities in a cell transplantation therapy model.3 Mouse tail-tip fibroblast-iPS cells (mesoderm origin) showed the highest tumorigenic propensity, whereas gastric epithelial cell- and hepatocyte-iPS cells (both are endoderm) showed lower propensities.3 It is therefore extremely important to establish human iPS cell lines from multiple origins and thoroughly examine the source impact on both the safety issues and their differentiation potentials. In addition, the ability to reprogram human hepatocytes is crucial for developing liver disease models using iPS cells, especially for certain liver diseases carrying acquired somatic mutations which occur only in hepatocytes of patients, but not in other cell types.1620
In the mouse, iPS cells have been generated from derivatives of all three embryonic germ layers, including mesodermal fibroblasts,6 epithelial cells of endodermal origin7 and ectodermal keratinocytes,8 whereas human iPS cells have been produced mostly from mesoderm (fibroblasts and blood cells) or from ectoderm (keratinocytes and neural stem cells).913,21,22 Here we show reprogramming of human primary hepatocytes (endoderm) to pluripotency. Hepatocyte-derived iPS cells appear indistinguishable from human embryonic stem cells in colony morphology, growth properties, expression of pluripotency-associated transcription factors and surface markers, and differentiation potential in embryoid body (EB) formation as well as teratoma assays. In addition these cells were able to directly differentiate into definitive endoderm, hepatic progenitors, and mature hepatocytes.
Our study lays the ground work necessary to elucidate the mechanisms of cellular reprogramming and to study the safety and efficacy of differentially originated human iPS cells in cell therapy.
Primary human hepatocytes were obtained from Lonza plated on collagen 1 and matrigel coated dishes, and cultured in serum containing WEM (Willians' Medium E), Gentamicin, Dexamethasone 10 mM, FBS 5%, L-Glutamine, Hepes 15mM, Insulin 4 mg/ml with 50ng/ml of HGF and EGF. Medium for culturing hES cells and iPS cells is Knockout DMEM supplemented with 20% KOSR, NEAA, 2-ME, GlutaMAX, 6 ng/ml basic fibroblast growth factor (all Invitrogen). hESC lines WA09 (H9) and WA01 (H1) (WiCell) were cultured on irradiated MEF feeder layers in ES medium. This study was done in accordance with Johns Hopkins ESCRO regulations and following a protocol approved by the Johns Hopkins IRB.
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Generation of Endoderm derived Human iPS cells from ...
Europe Approves Holoclar, the First Stem Cell-Based Medicinal Product
By raymumme
PARMA and MODENA, Italy, February 23, 2015 /PRNewswire/ --
The collaborationbetween a public excellent researchcenteranda solidprivate pharmaceuticalcompany allowed toachievean extraordinary result, entirely "made in Italy":the first medicinal productcontainingstem cellsapproved in the Western world
The European Commission has granted a conditional marketing authorization, under Regulation (EC) No 726/2004, to Holoclar, an advanced therapy based on autologous stem cells and capable to restore the eyesight of patients with severe cornea damage. Holoclar is manufactured by Holostem Terapie Avanzate (HolostemAdvanced Therapies) - a spin-off of the University of Modena and Reggio Emilia - at the Centre for Regenerative Medicine "Stefano Ferrari" (CMR) of the same University.
(Logo: http://photos.prnewswire.com/prnh/20150223/731609-a )
(Logo: http://photos.prnewswire.com/prnh/20150223/731609-b )
(Logo: http://photos.prnewswire.com/prnh/20150223/731609-c )
"Holoclaris theveryfirstmedicinalproductbased onstem cellsto beapproved andformallyregisteredin the Western world," states AndreaChiesi, Director of R&D Portfolio Management of Chiesi Farmaceutici S.p.A. and CEO of Holostem Terapie Avanzate. "This record," continues AndreaChiesi,"shows that thepartnershipbetween the public and privatesectorsis not only possible,butisprobably the best strategy for the development of stem cell-based regenerative medicine, particularly when autologous cells are used.Holostemisnowconsideredasabusiness modeltotranslate into clinicstheresultsobtained byscientific researchin this field." Underlying Holoclar are more than 20 years of excellence in research, conducted by a team of internationally renowned scientists in the field of epithelial stem cell biology aimed at clinical translation. European Directive 1394/2007 substantially equalizes advanced cell therapies to medicines and imposes, among other things, that cell cultures has to be manufactured only in GMP-certified facilities (GMP: Good Manufacturing Practice). Thanks to the investments of Chiesi Farmaceutici, the Centre for Regenerative Medicine in Modena - where Holostem operates - was certified as GMP compliant and continue to follow the path towards the registration of this newly developed advanced therapy.
"The authorization processhas been long andcomplex, butthe resultachievedtodayshows thatcellscan beculturedaccording topharmaceutical standardsappropriateto guaranteesafety and efficacy," adds Professor MicheleDeLuca, Scientific Director and co-founder of Holostem, as well as Director of the CMR of the University of Modena. "In addition,ina periodof great confusionabout the realtherapeutic possibilitiesof stem cells,such as the onewe are living in, being ableto demonstratethatstem cells can be definitely safe and successful in a controlled clinical settingismore important than ever." To explain how Holoclar works is Professor GraziellaPellegrini, Coordinator of cell therapy at CMR, as well as director of R&D and co-founder of Holostem, who authored, together with Professor De Luca, the research and designed the product development: "Afterdevelopingcell culturesbased onepithelial stem cellsfor the treatmentofvariousdisorders ofthestratifiedepithelia-from the skinfor full-thicknessburnsto the reconstructionof the urethra-wediscoveredthatthe stem cellsthat allowthe regenerationof the cornearesidein asmall areaatthe borderbetween the cornea(the transparent partat thecenter of the eye)andthe conjunctiva(the contiguous white part),which is called'the limbus'.Whenthermal or chemicalburnsof theocular surfacedamageirreversiblythisstemcellreserve,thecorneal surface-whichin ahealthy eyecompletely renews itself approximatelyeverysix/ninemonths-stopsregeneratingand the conjunctivagraduallybegins tocover thecorneawithawhite coating,thatprevents visionand causes chronicpainandinflammation.Ifinat leastone of the eyes of the patientevenasmallresidueofundamaged limbus is left,we areable to reconstructin a laboratorythe epitheliumthat covers thecorneal surface,thanks to thestem cells harvestedthrough a 1-2mmbiopsy.Thisgraftofepithelium-Holoclar, precisely-that looks likea kind ofcontactlens,is thentransplantedinto the patientandallows to obtain along-termtransparent corneaanda full recoveryof visual acuity,without causing anyrejection reaction,because itconsists of cellsof the patient him/herself."
This therapy, experimentally applied for the first time in humans in the nineties, and designated as orphan drug in 2008, thanks to the registration obtained today, in the near future will be available to all European patients who have suffered workplace injuries (caused, for example, by burnt lime, solvents or acids), domestic accidents (for example eye burns caused in adults and children by detergents or abrasive agents) or - as unfortunately reported by the press in the past few months - in the cases of assault with chemical agents.
Meanwhile, the research in Modena does not stop. The next goal of the team of Emilian researchers and entrepreneurs is to develop new advanced therapy products, such as the gene therapy for the treatment of epidermolysis bullosa, or "Butterfly disease", to date used successfully in the first two patients ever. And to develop new experimental and clinical protocols using different stem cells of stratified epithelia, such as conjunctiva, urethra, oral mucosa and respiratory epithelia.
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Europe Approves Holoclar, the First Stem Cell-Based Medicinal Product
Cambridge university researchers' breakthrough paves way for same sex couple babies
By JoanneRUSSELL25
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Researchers from Cambridge University have shown for the first time that it is possible to make human egg and sperm cells using skin from two adults of the same sex.
The scientific breakthrough may lead to a baby being made in a dish from the skin cells of two adults of the same sex, bringing hope to gay people.
The project, funded by the Wellcome Trust, was achieved at Cambridge University with Israels Weizmann Institute of Science.
The scientists used stem cell lines from embryos as well as from the skin of five different adults.
Ten different donor sources have been used so far and new germ-cell lines have been created from all of them, researchers said.
A gene called SOX1 has turned out to be critical in the process of reprogramming human cells, according to a report in a national newspaper.
The details of the technique were published in the journal Cell.
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Cambridge university researchers' breakthrough paves way for same sex couple babies
Why Stem Cell Therapy? – Video
By LizaAVILA
Why Stem Cell Therapy?
Dr. Bryn J. Henderson (DO, JD, FACPE, CIME) is visionary physician executive leading RMG. In this amazing education video, he is explaning clearly why patients should choose Stem Cell Therapy...
By: iManifestart
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Why Stem Cell Therapy? - Video
Stem Cell Research & Therapy | Full text | Aromatic …
By NEVAGiles23
Abstract Introduction
Aromatic (ar-) turmerone is a major bioactive compound of the herb Curcuma longa. It has been suggested that ar-turmerone inhibits microglia activation, a property that may be useful in treating neurodegenerative disease. Furthermore, the effects of ar-turmerone on neural stem cells (NSCs) remain to be investigated.
We exposed primary fetal rat NSCs to various concentrations of ar-turmerone. Thereafter, cell proliferation and differentiation potential were assessed. In vivo, nave rats were treated with a single intracerebroventricular (i.c.v.) injection of ar-turmerone. Proliferative activity of endogenous NSCs was assessed in vivo, by using noninvasive positron emission tomography (PET) imaging and the tracer [18F]-fluoro-L-thymidine ([18F]FLT), as well as ex vivo.
In vitro, ar-turmerone increased dose-dependently the number of cultured NSCs, because of an increase in NSC proliferation (P<0.01). Proliferation data were supported by qPCR-data for Ki-67 mRNA. In vitro as well as in vivo, ar-turmerone promoted neuronal differentiation of NSCs. In vivo, after i.c.v. injection of ar-turmerone, proliferating NSCs were mobilized from the subventricular zone (SVZ) and the hippocampus of adult rats, as demonstrated by both [18F]FLT-PET and histology (P<0.05).
Both in vitro and in vivo data suggest that ar-turmerone induces NSC proliferation. Ar-turmerone thus constitutes a promising candidate to support regeneration in neurologic disease.
Curcumin and ar-turmerone are the major bioactive compounds of the herb Curcuma longa. Although many studies have demonstrated curcumin to possess antiinflammatory and neuroprotective properties (reviewed by [1]), to date, the effects of ar-turmerone remain to be elucidated. For example, antitumor properties, exerted via the induction of apoptosis [2] and inhibition of tumor cell invasion [3], have been attributed to ar-turmerone. Park et al. [4,5] recently suggested that ar-turmerone also possesses antiinflammatory properties resulting from the blockade of key signaling pathways in microglia. Because microglia activation is a hallmark of neuroinflammation and is associated with various neurologic disorders, including neurodegenerative diseases [6,7] and stroke [8,9], ar-turmerone constitutes a promising therapeutic agent for various neurologic disorders.
The regenerative potential of endogenous neural stem cells (NSCs) plays an important role in neurodegenerative disease and stroke. Endogenous NSCs are mobilized by cerebral ischemia [10] as well as by various neurodegenerative diseases [11,12], although their intrinsic regenerative response is insufficient to enable functional recovery. The targeted (that is, pharmacologic) activation of endogenous NSCs has been shown to enhance self-repair and recovery of function in the adult brain in both stroke [13,14] and neurodegeneration [15]. Importantly, NSCs and microglia relevantly interact with each other, thereby affecting their respective functions [16,17].
Thus, with the perspective of ar-turmerone as a therapeutic option in mind, we investigated the effects of ar-turmerone on NSCs in vitro and in vivo.
NSCs were cultured from fetal rat cortex at embryonic day 14.5, as described previously [18]. Cells were expanded as monolayer cultures in serum-free DMEM/F12 medium (Life Technologies, Darmstadt, Germany) with N2 supplement (Gibco, Karlsruhe, Germany) and fibroblast growth factor (FGF2; 10ng/ml; Invitrogen, Karlsruhe, Germany) for 5days and were replated in a 24-well plate at 10,000 cells per cm2. FGF2 was included throughout the experiments.
Ar-turmerone (Fluka, Munich, Germany) was added to cultures at replating at concentrations of 0, 1.56, 3.125, 6.25, 12.5, and 25g/ml. All experiments were performed in triplicate. After 72hours, representative pictures were taken by using an inverted fluorescence phase-contrast microscope (Keyence BZ-9000E). Three images were taken per well, and cells were counted by using the software ImageJ with a threshold of 20 px (National Institutes of Health, Bethesda, MD, USA, Version 1.47k).
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Stem Cell Research & Therapy | Full text | Aromatic ...
Stem Cell Therapy Using Fat Cells – Howard Beach, Ozone Park, Queens NY – Dr. Benjamin Bieber, MD – Video
By Sykes24Tracey
Stem Cell Therapy Using Fat Cells - Howard Beach, Ozone Park, Queens NY - Dr. Benjamin Bieber, MD
Regenerative Medicine - Dr. Benjamin Bieber, MD - Howard Beach, Ozone Park, Queens NY http://www.crossbaypmr.com Phone: (718) 835-0100 Stem Cell Therapy Using Fat Cells Dr. Benjamin...
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Stem Cell Therapy Using Fat Cells - Howard Beach, Ozone Park, Queens NY - Dr. Benjamin Bieber, MD - Video
What is Bone Marrow Aspirate Concentrate (BMAC) in Stem Cell Therapy? – Video
By raymumme
What is Bone Marrow Aspirate Concentrate (BMAC) in Stem Cell Therapy?
Dr. McKenna explains bone marrow aspirate concentrate (BMAC). BMAC contains stem cells and growth factors that can build blood supply and heal tissue. For more information: http://www.rmiclinic.com...
By: Riordan-McKenna Institute
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What is Bone Marrow Aspirate Concentrate (BMAC) in Stem Cell Therapy? - Video
Stem Cell Therapy for Liver Failure Cirrhosis Kidney Damage – 6 Months After Stemcell Transplant – Video
By LizaAVILA
Stem Cell Therapy for Liver Failure Cirrhosis Kidney Damage - 6 Months After Stemcell Transplant
Bruce from Perth Australia give us an update 6 Months After his cord Mesenchymal stem cell treatment for Iiver cirrhosis, kidney complications in Thailand: More here: http://stemcellthailand.org/th...
By: Regeneration Center of Thailand
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Stem Cell Therapy for Liver Failure Cirrhosis Kidney Damage - 6 Months After Stemcell Transplant - Video
Ryan Benton Discusses Stem Cell Therapy for Duchenne’s Muscular Dystrophy – Video
By LizaAVILA
Ryan Benton Discusses Stem Cell Therapy for Duchenne #39;s Muscular Dystrophy
Ryan Benton is the first patient in the United States to receive human umbilical cord-derived mesenchymal stem cell therapy for Duchenne #39;s muscular dystrophy...
By: http://www.cellmedicine.com
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Ryan Benton Discusses Stem Cell Therapy for Duchenne's Muscular Dystrophy - Video
Mayo Clinic Radio: Cardiac Regeneration/Stop-Smoking Drug/Juicing
By LizaAVILA
Posted by Richard Dietman (@rdietman) 3 day(s) ago
Mayo Clinic Radio: Cardiac Regeneration/Stop-Smoking Drug/Juicing
On this weeks Mayo Clinic Radio,fixing a broken heart. Cardiac regeneration uses the bodys own stem cells to repair damage done by heart disease. Mayo Clinic cardiologist Dr. Atta Behfar explains. Also on the program, nicotine dependency expert Dr. Richard Hurt discusses results of a new study about the stop-smoking drug varenicline (Chantix). And Mayo Clinic registered dietitian Katherine Zeratsky explains the risks of juice-only diets.
Myth or Matter-of-Fact: Cardiac regeneration may someday replace the need for surgery to repair heart damage.
To listen to the program at 9 a.m. Saturday, February 21, clickhere.
Follow#MayoClinicRadioand tweet your questions.
Mayo Clinic Radio is available oniHeartRadio.
Mayo Clinic Radiois a weeklyone-hour radio program highlighting health and medical informationfrom Mayo Clinic.
To find and listen toarchived shows,click here.
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Mayo Clinic Radio: Cardiac Regeneration/Stop-Smoking Drug/Juicing
Luis and Kian King: Juvenile Krabbe Disease victims' mum in plea to help save her twin boys
By raymumme
A devoted mum whose sick twins desperately need a double bone marrow transplant has begged the nation: Please save my boys.
Luis and Kian King, seven, have Juvenile Krabbe Disease, which quickly ravages the nervous system and the youngsters are getting worse by the week.
Parents Laura, 36, and Dean, 38, know the odds are stacked against the boys, as doctors battle to find donors for the UKs first twin transplant, before they become too weak to survive treatment.
The average life expectancy of a child with the rare disease is just 12.
Laura pleaded: If you are not on the donor register you could be the match who can give my boys back their lives and their futures and you dont even realise it.
All of us are giant medicine bottles walking around with the ability to help others in their hour of need. It only takes 10 minutes to join the register and you can change a familys life forever.
Juvenile Krabbe Disease which affects fewer than one in a million children has left the boys, who also have cerebral palsy, unable to walk unaided.
Experts have warned that without a stem cell transplant they only have three years left with any real quality of life.
The disease will rob them of their sight and ability to feed themselves, causing them to suffer more and more pain until they can no longer breathe unaided.
With the boys just five years off the average life expectancy of 12, Laura admits their illness haunts her.
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Luis and Kian King: Juvenile Krabbe Disease victims' mum in plea to help save her twin boys
CardioWise Completes Installation of the First Totally Integrated CardioWise Analysis Software at National Institutes …
By Dr. Matthew Watson
Fayetteville, Arkansas (PRWEB) February 19, 2015
CardioWise, Inc. has completed development of the first fully integrated version of its Multiparametric Strain Analysis Software (MPSA) and has installed it at the National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI). MPSA software is being used in clinical research protocol number 12-H-0078, sponsored by the NHLBI entitled, Preliminary Assessment of Direct Intra-Myocardial Injection of Autologous Bone Marrow-derived Stromal Cells on Patients Undergoing Revascularization for Coronary Artery Disease (CAD) with Depressed Left Ventricular Function. The Principle Investigator is Dr. Keith A. Horvath, the Director of Cardiothoracic Surgery at the NHLBI and Chief of Cardiothoracic Surgery at Suburban Hospital, where he leads the NIH Heart Center. Details of the study are available here: http://clinicalstudies.info.nih.gov/cgi/wais/bold032001.pl?A_12-H-0078.html@mesenchymal@@@@.
The recently completed integrated version of CardioWise analysis software has been installed at the NIH; and, Dr. Justin Miller, and Dr. Ming Li, both research fellows in the Cardiothoracic Surgery Research Program of the NHLBI, have been trained on its operation and use. They were assigned to the project by Dr. Horvath and Dr. Andrew Arai, Chief of the Advanced Cardiovascular Imaging Research Group in the NHLBIs Division of Intramural Research. CardioWise has completed validation testing of its software and the analyses of the first two patient cardiac MRI (CMR) data sets are in process. The patients who enrolled in the protocol received one baseline CMR scan and three additional follow-up CMR scans. Those CMR scans are being analyzed by CardioWise analysis software and the analyses will be compared to determine whether stem cell injections can improve the contractile function of the heart muscle by repairing damaged tissue.
The installation at the NIH under a Beta site agreement signed in 2014 marks the first clinical test of CardioWise MPSA software outside of Washington University School of Medicine in St. Louis, where it was developed. CardioWise has obtained the exclusive worldwide license for the patent-pending software and accompanying normal hearts database from Washington University in St. Louis. The companys MPSA software is uniquely capable of analyzing the three-dimensional motion of the heart that is acquired from cardiac MRI images and then comparing the analysis at 15,300 points to the motion of a normal heart model. The analysis detects portions of the heart that are moving abnormally and demonstrates to what degree the heart muscle has been affected. Since MRI uses no ionizing radiation or contrast, it is completely non-invasive and poses minimal risk to the patient. This allows the patient to be followed through the course of treatment and to measure outcomes of interventions such as the stem cell therapy currently being evaluated. In the near future, CardioWise MPSA may aid doctors to determine what intervention, such as surgery, stent insertion, or drug is most appropriate for the patient who presents with cardiovascular disease symptoms.
CardioWise is commercializing patent-pending, non-invasive Cardiac Magnetic Resonance Imaging (CMR) analysis software that produces a quantified 4D image model of the human heart, called Multiparametric Strain Analysis (MPSA). CardioWise heart analysis software combined with cardiac MRI is a single diagnostic test that is able to provide quantitative analysis of the myocardium, arteries and valves with an unprecedented level of detail. It has the opportunity to become the new gold standard of care for heart health analysis. CardioWise is a VIC Technology Venture Development portfolio company.
Stem Cell Therapy Using Bone Marrow – Howard Beach, Ozone Park, Queens NY – Dr. Benjamin Bieber, MD – Video
By NEVAGiles23
Stem Cell Therapy Using Bone Marrow - Howard Beach, Ozone Park, Queens NY - Dr. Benjamin Bieber, MD
http://www.crossbaypmr.com Stem Cell Therapy Using Bone Marrow - Howard Beach, Ozone Park, Queens NY - Dr. Benjamin Bieber, MD - Regenerative Medicine Phone:...
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A good night's sleep keeps your stem cells young
By LizaAVILA
Under normal conditions, many of the different types of tissue-specific adult stem cells, including hematopoietic stem cells, exist in a state or dormancy where they rarely divide and have very low energy demands. "Our theory was that this state of dormancy protected hematopoietic stem cells from DNA damage and therefore protects them from premature aging," says Dr. Michael Milsom, leader of the study.
However, under conditions of stress, such as during chronic blood loss or infection, hematopoietic stem cells are driven into a state of rapid cell division in order to produce new blood cells and repair the damaged tissue. "It's like forcing you out of your bed in the middle of the night and then putting you into a sports car and asking you to drive as fast as you can around a race circuit while you are still half asleep," explains Milsom. "The stem cells go from a state of rest to very high activity within a short space of time, requiring them to rapidly increase their metabolic rate, synthesize new DNA and coordinate cell division. Suddenly having to simultaneously execute these complicated functions dramatically increases the likelihood that something will go wrong."
Indeed, experiments described in the study show that the increased energy demands of the stem cells during stress result in elevated production of reactive metabolites that can directly damage DNA. If this happens at the same time that the cell is trying to replicate its DNA, then this can cause either the death of the stem cell, or potentially the acquisition of mutations that may cause cancer.
Normal stem cells can repair the majority of this stress-induced DNA damage, but the more times you are exposed to stress, the more likely it is that a given stem cell will inefficiently repair the damage and then die or become mutated and act as a seed in the development of leukemia. "We believe that this model perfectly explains the gradual accumulation of DNA damage in stem cells with age and the associated reduction in the ability of a tissue to maintain and repair itself as you get older," Milsom adds.
In addition, the study goes on to examine how this stress response impacts on a mouse model of a rare inherited premature aging disorder that is caused by a defect in DNA repair. Patients with Fanconi anemia suffer a collapse of their blood system and have an extremely high risk of developing cancer. Mouse models of Fanconi anemia have exactly the same DNA repair defect as found in human patients but the mice never spontaneously develop the bone marrow failure observed in nearly all patients.
"We felt that stress induced DNA damage was the missing ingredient that was required to cause hematopoietic stem cell depletion in these mice," says Milsom. When Fanconi anemia mice were exposed to stimulation mimicking a prolonged viral infection, they were unable to efficiently repair the resulting DNA damage and their stem cells failed. In the same space of time that normal mice showed a gradual decline in hematopoietic stem cell numbers, the stem cells in Fanconi anemia mice were almost completely depleted, resulting in bone marrow failure and an inadequate production of blood cells to sustain life.
"This perfectly recapitulates what happens to Fanconi anemia patients and now gives us an opportunity to understand how this disease works and how we might better treat it," commented Milsom.
Prof. Dr. Andreas Trumpp, director of HI-STEM and head of the Division of Stem Cells and Cancer at the DKFZ believes that this work is a big step towards understanding a range of age-related diseases. "The novel link between physiologic stress, mutations in stem cells and aging is very exciting," says Trumpp, a co-author of the study. "By understanding the mechanism via which stem cells age, we can start to think about strategies to prevent or at least reduce the risk of damaged stem cells which are the cause of aging and the seed of cancer."
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The above story is based on materials provided by German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ). Note: Materials may be edited for content and length.
The Story Of Sharing Americas Marrow
By Sykes24Tracey
(L-R) Taylor Shorten, Sam Kimura and Alex Kimura (photo courtesy of SAM)
With the support of Delete Blood Cancer DKMS, the two sisters and their best friend Taylor Shorten began their road trip in January to visit all 50 states at churches, colleges, concerts and everything in between to promote increased awareness of blood cancer and blood diseases, in addition to finding donors for Sam and thousands of others.
Despite a busy, sometimes exhausting tour driving across America in a van named Maggie, Sam was able to spend a few moments to talk more about their cause and how people can potentially save someones life.
Alex and I came up with the concept of Sharing Americas Marrow about a year ago. We had been doing bone marrow donor drives ever since my diagnosis of severe aplastic anemia in 2010, but we wanted to do something really big. We enjoyed registering donors and knowing that each person has the potential to be a life-saving match, we decided to create a campaign around that idea. SAM evolved into a 50-state tour around the country with our best friend, Taylor Shorten, to register 50,000 potential donors.
We are working with Delete Blood Cancer DKMS to register potential donors. Delete Blood Cancer provides us with registration supplies in addition to testing each donor kit in the lab for potential donors to be listed on the registry.
Related: Five Healthy Foods For Your Brain
A Donor Jam is what we call a bone marrow donor drive. Its an event where people fill out a registration form and complete a cheek swab to get listed as a potential donor on the national registry. Bone marrow donor drive can sound intense, so we wanted to lighten it up a little and make it sound more fun, because saving lives is just thatfun!
Other groups can absolutely host a Donor Jam with us. With the help of Delete Blood Cancer, we can supply people with registration materials, training on how to register donors, flyers/promotional items to get the word out, etc. so that people can host their very own SAM Donor Jam.
In most cases, the success of allogeneic transplantation depends in part on how well the HLA antigens of the donors stem cells match those of the recipients stem cells. The higher the number of matching HLA antigens, the greater the chance that the patients body will accept the donors stem cells. In general, patients are less likely to develop a complication known as graft-versus-host disease (GVHD) if the stem cells of the donor and patient are closely matched. Thus, finding a perfect match (also known as a 10/10 match) for a patient drastically minimizes the risk that the patient will reject the transplant or develop post-transplant complications.
We just felt that the van had the essence of a Maggie. We didnt necessarily choose the name, the name chose us.
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The Story Of Sharing Americas Marrow
Changing stem cell structure may help fight obesity
By Dr. Matthew Watson
Scientists have found that reducing the size of tiny hair like structures on stem cells stops them turning into fat. The discovery could be used to develop a way of preventing obesity.
The research, conducted at Queen Mary University of London (QMUL), found that a slight regulation in the length of primary cilia, small hair-like projections found on most cells, prevented the production of fat cells from human stem cells taken from adult bone marrow.
Part of the process by which calories are turned into fat involves adipogenesis, the differentiation of stem cells into fat cells. The researchers showed that during this process of adipogenesis, the length of primary cilia increases associated with movement of specific proteins onto the cilia. Furthermore, by genetically restricting this cilia elongation in stem cells the researchers were able to stop the formation of new fat cells.
Recent research has found that many conditions including kidney disease, blindness, problems with bones and obesity can be caused by defects in primary cilia.
Melis Dalbay, co-author of the research from the School of Engineering and Materials Science at QMUL, said: This is the first time that it has been shown that subtle changes in primary cilia structure can influence the differentiation of stem cell into fat. Since primary cilia length can be influenced by various factors including pharmaceuticals, inflammation and even mechanical forces, this study provides new insight into the regulation of fat cell formation and obesity.
Professor Martin Knight, a bioengineer and lead author of the research, said: This research points towards a new type of treatment known as cilia-therapy where manipulation of primary cilia may be used in future to treat a growing range of conditions including obesity, cancer, inflammation and arthritis.
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The above story is based on materials provided by University of Queen Mary London. Note: Materials may be edited for content and length.
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Dr Ellis hosts seminar on Stem Cell Therapy & Facial Rejuvenation – Video
By Sykes24Tracey
Dr Ellis hosts seminar on Stem Cell Therapy Facial Rejuvenation
Dr. Dan Eglinton of Asheville Biologics and Orthopaedics, Dr. Sean Whalen and Dr. Paul Mogannam of Flexogenics and Dr. Laura Ellis of medAge speak about Stem Cell Therapy and skin ...
By: Dr. Laura Ellis
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Dr Ellis hosts seminar on Stem Cell Therapy & Facial Rejuvenation - Video
Dr. Raj at Beverly Hills Orthopedic Institute Achieving 80% Success with Stem Cell Therapy
By JoanneRUSSELL25
Beverly Hills, CA (PRWEB) February 17, 2015
The top stem cell clinic in Los Angeles and Beverly Hills is now achieving 80% success with stem cell therapy for all types of arthritis and soft tissue indications. This includes hip, knee, shoulder, elbow and ankle injections for helping patients achieve pain relief and avoid surgery. Call (310) 438-5343 for more information on the treatment options available and scheduling.
Dr. Raj, who was recently named a Super Doc Southern California for the 4th year in a row, has been performing stem cell therapy on patients for years. This includes athletes, weekend warriors, celebrities, executives, senior citizens and students as well.
There are two methods offered for the treatment, one of which is Bone Marrow derived. This includes harvesting bone marrow from the patient's hip area, and then the material is immediately processed to concentrate the stem cells and growth factors. the fluid is then injected into the problem area. An internal review at Beverly Hills Orthopedic Institute has shown that 80% of patients achieve excellent pain relief and increased functional abilities. This includes getting back to athletics, recreational activities and walking more.
The second method of treatment involves amniotic derived stem cell rich injections. The amniotic fluid is processed at an FDA regulated lab, with no fetal tissue being involved and no embryonic stem cells at all. Amniotic fluid has been used tens of thousands of times worldwide for many indications, and contains growth factors, hyaluronic acid and stem cells.
Indications for the treatment include tennis and golfer's elbow, plantar fasciitis, degenerative arthritis of the hip, knee, shoulder, elbow, ankle, ligament injuries, and tendonitis of the shoulder, knee, achilles and more.
Dr. Raj is a Double Board Certified orthopedic doctor in Los Angeles and serves as an ABC News Medical Correspondent and a WebMD expert. He is called frequently by networks for his opinion on orthopedic matters, and is on the Medical Advisory Board for R3 Stem Cell.
For more information and scheduling with the top stem cell clinic in Los Angeles and Beverly Hills, call (310) 438-5343.
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Dr. Raj at Beverly Hills Orthopedic Institute Achieving 80% Success with Stem Cell Therapy
Global Stem Cells Group Announces Alliance with Advancells
By raymumme
MIAMI (PRWEB) February 16, 2015
Global Stem Cells Group, Inc. announced an alliance with India-based stem cells company Advancells.com, to share protocols and expand GSCG operations in the India subcontinent with stem cell training and a new treatment center.
Advancells, a pioneer stem cell company with some of the most advanced protocols in the world, focuses on therapeutic applications of regenerative medicine primarily used in stem cells generated from the patients own body. Advancells delivers technologies for safe and effective treatments using their flagship technologies including autologous stem cell therapy from bone marrow and adipose tissue to patients worldwide; Global Stem Cells Group will implement some Advancells technologies in the Regenestem Netowork of worldwide clinics.
Since 2005, Advancells has safely treated thousands of patients for a range of diseases and medical conditions in its various clinics around the globe. Advancells is supported by physicians, stem cell experts and clinical research scientists to continually monitor and improve the effectiveness of its quality management system with excellence and innovation.
"We are pleased to partner with Global Stem Cells Group, to combine our knowledge and expand our ability to bring stem cell medicine to patients worldwide, says Advancells CEO Vipul Jain. I am looking forward to a long and productive alliance.
For more information, visit the Global Stem Cells Group website, email bnovas(AT)stemcellsgroup.com, or call 305-224-1858.
About the Global Stem Cells Group:
Global Stem Cells Group, Inc. is the parent company of six wholly owned operating companies dedicated entirely to stem cell research, training, products and solutions. Founded in 2012, the company combines dedicated researchers, physician and patient educators and solution providers with the shared goal of meeting the growing worldwide need for leading edge stem cell treatments and solutions. With a singular focus on this exciting new area of medical research, Global Stem Cells Group and its subsidiaries are uniquely positioned to become global leaders in cellular medicine.
Global Stem Cells Groups corporate mission is to make the promise of stem cell medicine a reality for patients around the world. With each of GSCGs six operating companies focused on a separate research-based mission, the result is a global network of state-of-the-art stem cell treatments.
About the Regenestem Network:
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Global Stem Cells Group Announces Alliance with Advancells
Hip arthritis 3.5 years after stem cell therapy by Harry Adelson, N.D. – Video
By JoanneRUSSELL25
Hip arthritis 3.5 years after stem cell therapy by Harry Adelson, N.D.
Bobby describes his outcome 3.5 years after stem cell therapy for his arthritic hip by Harry Adelson, N.D. http://www.docereclinics.com.
By: Harry Adelson, N.D.
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Hip arthritis 3.5 years after stem cell therapy by Harry Adelson, N.D. - Video