Joseph Itskovitz-Eldor

Technion - Israel Institute of Technology, H̱efa, Haifa District, Israel

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Publications (195)1028.97 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) have the capacity to differentiate into any specialized cell type, including cardiomyocytes. Therefore, hESC-derived and hiPSC-derived cardiomyocytes (hESC-CMs and hiPSC-CMs, respectively) offer great potential for cardiac regenerative medicine. Unlike some organs, the heart has a limited ability to regenerate, and dysfunction resulting from significant cardiomyocyte loss under pathophysiological conditions, such as myocardial infarction (MI), can lead to heart failure. Unfortunately, for patients with end-stage heart failure, heart transplantation remains the main alternative, and it is insufficient, mainly because of the limited availability of donor organs. Although left ventricular assist devices are progressively entering clinical practice as a bridge to transplantation and even as an optional therapy, cell replacement therapy presents a plausible alternative to donor organ transplantation. During the past decade, multiple candidate cells were proposed for cardiac regeneration, and their mechanisms of action in the myocardium have been explored. The purpose of this article is to critically review the comprehensive research involving the use of hESCs and hiPSCs in MI models and to discuss current controversies, unresolved issues, challenges, and future directions. Copyright © 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
    The Canadian journal of cardiology 11/2014; 30(11):1279-1287. · 3.12 Impact Factor
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    ABSTRACT: Background We previously reported that induced Pluripotent Stem Cell-derived cardiomyocytes (iPSC-CM) manifest beat rate variability (BRV) resembling heart rate variability (HRV) in human sinoatrial node (SAN). We now hypothesized the BRV-HRV continuum originates in pacemaker cells. Objective To investigate whether cellular BRV is a source of HRV dynamics, we hypothesized three-levels of interaction among different cardiomyocyte entities: (1) single pacemaker cells, (2) networks of electrically coupled pacemaker cells and (3) in situ SAN. Methods We measured BRV/HRV properties in single pacemaker cells, iPSC-derived contracting embryoid bodies (EBs) and electrocardiograms from the same individual. Results Pronounced BRV/HRV were present at all three levels. Coefficient of variance (COV) of inter-beat intervals (IBI) and Poincaré plot SD1 and SD2 in single cells were 20x > EBs (P<0.05) and in situ heart (the latter two were similar, P>0.05). We also compared BRV magnitude among single cells, small (~5-10 cells) and larger EBs (>10 cells): BRV indices progressively increased (P<0.05) as cell number decreased. Disrupting intracellular Ca2+ handling markedly augmented BRV magnitude, revealing a unique bi-modal firing pattern, suggesting intracellular mechanisms contribute to BRV/HRV and the fractal behavior of heart rhythm. Conclusions The decreased BRV magnitude in transitioning from single cell to EB suggests HRV of hearts in situ originates from summation and integration of multiple cell-based oscillators. Hence, complex interactions among multiple pacemaker cells and intracellular Ca2+ handling determine HRV in humans and isolated cardiomyocyte networks.
    Heart Rhythm 10/2014; · 5.05 Impact Factor
  • Hagit Domev, Irina Milkov, Joseph Itskovitz-Eldor, Ayelet Dar
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    ABSTRACT: Isolated microvessel-residing pericytes and pericytes from human pluripotent stem cells (hPSCs) exhibit mesenchymal stem cell-like characteristics and therapeutic properties. Despite growing interest in pericyte-based stem cell therapy, their immunogenicity and immunomodulatory effects on nonactivated T cells are still poorly defined, in particular those of vasculogenic hPSC pericytes. We found that tissue-embedded and unstimulated cultured hPSC- or tissue-derived pericytes constitutively expressed major histocompatibility complex (MHC) class I and the inhibitory programmed cell death-ligand 1/2 (PD-L1/2) molecules but not MHC class II or CD80/CD86 costimulatory molecules. Pretreatment with inflammatory mediators failed to induce an antigen-presenting cell-like phenotype in stimulated pericytes. CD146(+) pericytes from hPSCs did not induce activation and proliferation of allogeneic resting T cells independent of interferon (IFN)-γ prestimulation, similarly to pericytes from human brain or placenta. Instead, pericytes mediated a significant increase in the frequency of allogeneic CD25(high)FoxP3(+) regulatory T cells when cocultured with nonactivated peripheral blood T cells. Furthermore, when peripheral blood CD25(high) regulatory T cells (Tregs) were depleted from isolated CD3(+) T cells, pericytes preferentially induced de novo formation of CD4(+)CD25(high)FoxP3(+)CD127(-), suppressive regulatory T cells. Constitutive expression of PD-L1/2 and secretion of transforming growth factor-β by hPSC pericytes directly regulated generation of pericyte-induced Tregs. Pericytes cotransplanted into immunodeficient mice with allogeneic CD25(-) T cells maintained a nonimmunogenic phenotype and mediated the development of functional regulatory T cells. Together, these findings reveal a novel feature of pericyte-mediated immunomodulation distinguished from immunosuppression, shared by native tissue pericytes and hPSC pericytes, and support the notion that pericytes can be applied for allogeneic cell therapy.
    STEM CELLS TRANSLATIONAL MEDICINE 09/2014; · 3.60 Impact Factor
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    ABSTRACT: Extracellular matrix (ECM) has been utilized as a biological scaffold for tissue engineering applications in a variety of body systems, due to its bioactivity and biocompatibility. In the current study we developed a modified protocol for the derivation of mesenchymal progenitor cells (MPCs) from human embryonic stem cells as well as human induced pluripotent stem cells originating from hair follicle keratinocytes (HFKTs). ECM was produced from these MPCs and characterized in compare to adipose mesenchymal stem cells (aMSCs) ECM. Exploiting an electrospun biodegradable nanofiber layer (NFL) which provide mechanical support, and an optimized decellularization treatment we were able to generate an available "off-the shelf" implantable product (NFL-ECM). Using rat subcutaneous transplantation model we demonstrate that this stem cell derived construct is biocompatible, biodegradable and provides great potential for tissue regeneration.
    Tissue Engineering Part A 09/2014; · 4.07 Impact Factor
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    ABSTRACT: To characterize, using 3D transperineal ultrasound, the appearance, position, and dimensions of mesh implants following minimally invasive abdominal sacrocolpopexy. In women who underwent sacrocolpopexy, mesh was evaluated at rest and on maximal valsalva, on all 3D orthogonal planes and rendered views. Mesh dimensions were obtained by 3D processing in the midsagittal and coronal plane (anterior, posterior, sacral arm), and analyzed offline, blinded to clinical data. Overall 62 women, mean age 58.4 years (range 42-79) were evaluated at 9 months mean (range 1-26) following surgery. The anterior arm of the mesh was caudal to the lowermost point of descent of the anterior compartment in 56 (90%), equally positioned in 5 (8.1%) and cranial in 1. The posterior arm was caudal in 44 (71%), equally positioned in 16 (25.8%) and cranial in 2 (3.2%). The Y connection and the sacral arm of the mesh could not be adequately seen due to ultrasound physics, due to large recurrent rectoceles, due to echogenic stools or from folding of mesh remnants. Folding of the mesh was seen in 46 (74.2%) women, of the anterior arm in 5 (8.1%) and of the posterior arm in 23 (37.1%). Folding occurred caudally in 26 (56.5%), proximally in 11 (23.9%) and in both areas in 9 (19.6%). There were no erosions. Mesh visualization following minimally invasive abdominal sacrocolpopexy procedures using transperineal 3D/4D ultrasound is feasible. Studies are needed to evaluate the correlation between ultrasound measures and prolapse recurrence or mesh erosions.
    Ultrasound in Obstetrics and Gynecology 01/2014; · 3.56 Impact Factor
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    ABSTRACT: Adenosine to Inosine (A-to-I) RNA editing is a post-transcriptional, site specific modification process, catalyzed by Adenosine Deaminase Acting on RNA (ADAR) gene family members. Since ADARs act on double strand RNA, most A-to-I editing occurs within repetitive elements, particularly Alu elements, as the result of the inherent property of these sequences to fold and form double strands. A-to-I editing was recently implicated in the regulation of human embryonic stem cells (hESC). Spontaneous and neuronal differentiation of hESC was shown to result in a decrease in A-to-I editing levels. Knockdown of ADAR1 in hESCs results in elevation of the expression of differentiation related genes. In addition, we found that hESCs are not susceptible to ADAR1 overexpression. The current study shows that the editing levels of induced pluripotent stem cells (iPSCs) change throughout reprogramming, from a source cell level to a level similar to that of hESCs. Up or down regulation of the ADAR1 level in human foreskin fibroblast (HFF) cells prior to induction of reprogramming results in varied reprogramming efficiencies. Furthermore, HFF-iPSC early clones derived from source cells in which the ADAR1 level was downregulated, lose their iPSC properties shortly after iPSC colony formation and exhibit instead characteristics of cancer cells. Taken together, our results imply a role for A-to-I editing in the regulation of pluripotency induction as well as in the maintenance of early iPSC properties.
    Stem cells and development 11/2013; · 4.15 Impact Factor
  • Shtrichman Ronit, Germanguz Igal, Joseph Itskovitz-Eldor
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    ABSTRACT: Human induced pluripotent stem cells (hiPSCs) have great potential as a robust source of progenitors for regenerative medicine. The novel technology also enables the derivation of patient-specific cells for applications to personalized medicine, such as for personal drug screening and toxicology. However, the biological characteristics of iPSCs are not yet fully understood and their similarity to human embryonic stem cells (hESCs) is still unresolved. Variations among iPSCs, resulting from their original tissue or cell source, and from the experimental protocols used for their derivation, significantly affect epigenetic properties and differentiation potential. Here we review the potential of iPSCs for regenerative and personalized medicine, and assess their expression pattern, epigenetic memory and differentiation capabilities in relation to their parental tissue source. We also summarize the patient-specific iPSCs that have been derived for applications in biological research and drug discovery; and review risks that must be overcome in order to use iPSC technology for clinical applications.
    Current Molecular Medicine 05/2013; · 4.20 Impact Factor
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    ABSTRACT: Proper expression and function of the cardiac pacemaker is a critical feature of heart physiology. Two main mechanisms have been proposed: (i) the "voltage-clock," where the hyperpolarization-activated funny current If causes diastolic depolarization that triggers action potential cycling; and (ii) the "Ca(2+) clock," where cyclical release of Ca(2+) from Ca(2+) stores depolarizes the membrane during diastole via activation of the Na(+)-Ca(2+) exchanger. Nonetheless, these mechanisms remain controversial. Here, we used human embryonic stem cell-derived cardiomyocytes (hESC-CMs) to study their autonomous beating mechanisms. Combined current- and voltage-clamp recordings from the same cell showed the so-called "voltage and Ca(2+) clock" pacemaker mechanisms to operate in a mutually exclusive fashion in different cell populations, but also to coexist in other cells. Blocking the "voltage or Ca(2+) clock" produced a similar depolarization of the maximal diastolic potential (MDP) that culminated by cessation of action potentials, suggesting that they converge to a common pacemaker component. Using patch-clamp recording, real-time PCR, Western blotting, and immunocytochemistry, we identified a previously unrecognized Ca(2+)-activated intermediate K(+) conductance (IKCa, KCa3.1, or SK4) in young and old stage-derived hESC-CMs. IKCa inhibition produced MDP depolarization and pacemaker suppression. By shaping the MDP driving force and exquisitely balancing inward currents during diastolic depolarization, IKCa appears to play a crucial role in human embryonic cardiac automaticity.
    Proceedings of the National Academy of Sciences 04/2013; · 9.81 Impact Factor
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    ABSTRACT: Maternal infection or inflammation may induce fetal inflammatory responses associated with fetal injury and cerebral palsy. We sought to assess the inflammation-associated neuroprotective potential of prophylactic N-acetyl-cysteine (NAC). We examined the effect of NAC on prevention of maternal lipopolysaccharide (LPS)-induced neonatal brain injury using magnetic resonance imaging. Pregnant Sprague Dawley dams (n = 5-8) at embryonic day 18 received intraperitoneal injection of LPS or saline at time 0. Animals were randomized to receive 2 intravenous injections of NAC or saline (time -30 and 120 minutes). Pups were delivered spontaneously and allowed to mature until postnatal day 25. Female offspring were examined by magnetic resonance brain imaging and analyzed using voxel-based analysis after spatial normalization. T2 relaxation time was used to assess white matter injury and diffusion tensor imaging for apparent diffusion coefficient (ADC) to assess white and gray matter injury. Offspring of LPS-treated dams exhibited significantly increased T2 levels and increased ADC levels in white and gray matter (eg, hypothalamus, motor cortex, corpus callosum, thalamus, hippocampus), consistent with diffuse cerebral injury. In contrast, offspring of NAC-treated LPS dams demonstrated similar T2 and ADC levels as control in both white and gray matter. Maternal NAC treatment significantly reduced evidence of neonatal brain injury associated with maternal LPS. These studies suggest that maternal NAC therapy may be effective in human deliveries associated with maternal/fetal inflammation.
    American journal of obstetrics and gynecology 03/2013; 208(3):213.e1-6. · 3.28 Impact Factor
  • Naama Zeevi-Levin, Joseph Itskovitz-Eldor, Ofer Binah
    Future medicinal chemistry 03/2013; 5(4):363-6. · 3.31 Impact Factor
  • Ofer Binah, Amir Weissman, Joseph Itskovitz-Eldor, Michael R Rosen
    Heart rhythm: the official journal of the Heart Rhythm Society 02/2013; · 4.56 Impact Factor
  • Ayelet Dar, Joseph Itskovitz-Eldor
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    ABSTRACT: Vascularization of injured tissues or artificial grafts is a major challenge in tissue engineering, stimulating a continued search for alternative sources for vasculogenic cells and the development of therapeutic strategies. Human pluripotent stem cells (hPSCs), either embryonic or induced, offer a plentiful platform for the derivation of large numbers of vasculogenic cells, as required for clinical transplantations. Various protocols for generation of vasculogenic smooth muscle cells (SMCs) from hPSCs have been described with considerably different SMC derivatives. In addition, we recently identified hPSC-derived pericytes, which are similar to their physiological counterparts, exhibiting unique features of blood vessel-residing perivascular cells, as well as multipotent mesenchymal precursors with therapeutic angiogenic potential. In this review we refer to methodologies for the development of a variety of perivascular cells from hPSCs with respect to developmental induction, differentiation capabilities, potency and their dual function as mesenchymal precursors. The therapeutic effect of hPSC-derived perivascular cells in experimental models of tissue engineering and regenerative medicine are described and compared to those of their native physiological counterparts. Copyright © 2013 John Wiley & Sons, Ltd.
    Journal of Tissue Engineering and Regenerative Medicine 01/2013; · 4.43 Impact Factor
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    ABSTRACT: Maternal infection is associated with oxidative stress (OS) and inflammatory responses. We have previously shown that maternal exposure to lipopolysaccharide (LPS) at E18 alters the subsequent offspring immune response. As immune responses are mediated, in part, by OS, we sought to determine if maternal inflammation during pregnancy programs offspring OS and C-reactive protein (CRP) levels. Pregnant Sprague-Dawley rats received intraperitoneal (i.p.) injections of saline or LPS at 18 days’ gestation (n = 4), and pups delivered spontaneously at term. At postnatal day 24, male and female offspring received i.p. injection of LPS. Serum lipid peroxides formation (PD) and CRP levels were determined before and at 4 h following the LPS injection. Pups of LPS-exposed dams had significantly higher basal OS (PD 29.4 ± 5.4 v. 10.1 ± 4.8 nmol/ml) compared with controls. In response to LPS, CRP levels (20.4 ± 2.8 v. 5.7 ± 1.0 ng/ml) were significantly higher among pups of LPS-exposed dams than controls. Prenatal maternal exposure to LPS increases baseline OS levels in neonates and CRP levels in response to LPS. These results suggest that maternal inflammation during the antenatal period may induce long-term sequelae in the offspring that may predispose to adult disease.
    Journal of Developmental Origins of Health and Disease. 10/2012; 3(05).
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    ABSTRACT: The mechanisms underlying the immunomodulatory effects of mesenchymal stem cells (MSCs) have been essentially studied in conditions of strong T cell activation that represents extreme situation and induces rapid death of activated lymphocytes. The objective of this study was to investigate these mechanisms in absence of additional polyclonal activation. In cocultures of peripheral mononuclear blood cells with hMSC, we observed a striking decreased expression of CD8 level on CD8+ cells, together with decreased CD28 and CD44 expression and impaired IFN-gamma and Granzyme B production. This effect was specific to hMSCs, since it was not observed with several other cell lines. Down-regulation of CD8 expression required CD14+ monocytes in direct contact with the CD8+ cells, while the effects of hMSCs on the CD14+ cells were essentially mediated by soluble factors. The CD14+ monocytes exhibited a tolerogenic pattern when co-cultured with hMSCs, with a clear decrease in CD80 and CD86 co-stimulatory molecules, and an increase in the inhibitory receptors ILT-3 and ILT-4. MSC-preconditioned CD8+ cells had similar effects on monocytes and were able to inhibit lymphocyte proliferation. Injection of human MSCs in humanized NSG mice showed similar trends, in particular decreased CD44 and CD28 on human immune cells. Altogether, our study demonstrates a new immunomodulation mechanism of action of hMSCs through the modulation of CD8+ cells towards a non-cytotoxic/suppressive phenotype. This mechanism of action has to be taken into account in clinical trials, where it should be beneficial in grafts and autoimmune diseases, but potentially detrimental in malignant diseases.
    Journal of Cell Science 07/2012; · 5.88 Impact Factor
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    Atara Novak, Avraham Lorber, Joseph Itskovitz-Eldor, Ofer Binah
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    ABSTRACT: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic cardiac disorder characterized by life-threatening arrhythmias induced by physical or emotional stress, in the absence structural heart abnormalities. The arrhythmias may cause syncope or degenerate into cardiac arrest and sudden death which usually occurs during childhood. Recent studies have shown that CPVT is caused by mutations in the cardiac ryanodine receptor type 2 (RyR2) or calsequestrin 2 (CASQ2) genes. Both proteins are key contributors to the intracellular Ca(2+) handling process and play a pivotal role in Ca(2+) release from the sarcoplasmic reticulum to the cytosol during systole. Although the molecular pathogenesis of CPVT is not entirely clear, it was suggested that the CPVT mutations promote excessive sarcoplasmic reticulum Ca(2+) leak, which initiates delayed afterdepolarizations (DADs) and triggered arrhythmias in cardiac myocytes. The recent breakthrough discovery of induced pluripotent stem cells (iPSC) generated from somatic cells (e.g. fibroblasts, keratinocytes) now enables researches to investigate mutated cardiomyocytes generated from the patient's iPSC. To this end, in the present article we review recent studies on CPVT iPSC-derived cardiomyocytes, thus demonstrating in the mutated cells catecholamine-induced DADs and triggered arrhythmias.
    Rambam Maimonides medical journal. 07/2012; 3(3):e0015.
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    ABSTRACT: Objectives: To assess the role of transperineal ultrasound in the post - operative evaluation of patients undergoing colpocleisis. Methods: Patients who underwent colpocleisis between July 2009 and January 2011 completed the Pelvic Floor Distress Inventory questionnaire (PFDI-20), and underwent the pelvic organ prolapse quantification (POP-Q) exam and 4D transperineal ultrasound. Volumes were analyzed offline, for pelvic organ descent, levator hiatal dimensions, levator avulsion trauma, and the location of the colpocleisis scar. Statistical analysis was performed using SPSS software. Results: The study included 16 women, mean age 75.7 ± 2.9 years, median BMI 28 (21-32), and median parity 2 (0-5, 1 nulliparous). Nine (56.2%) were post-hysterectomy. The median interval from surgery to ultrasound examination was 6.5 months (range: 2-19). Most patients did not have symptoms of prolapse. The median Pelvic Organ Prolapse Distress Inventory (POPDI-6) score was 37.5 (range 0-75), and the median post-operative clinical POP-Q stage was 1 (0-2). Ultrasound demonstrated clear visualization in all patients. Ten had avulsion defects (6 were bilateral). Ultrasound estimated greater prolapse descent for all compartments when compared with the clinical examination. However, this difference was significant for anterior and posterior, but not for apical descent. In two women urethral diverticulum was detected on ultrasound; it was neither symptomatic nor clinically apparent. Conclusions: 4D transperineal ultrasound seems to be a potentially effective tool for the evaluation of vaginal anatomical and functional changes following colpocleisis surgery. Future investigation of the association between ultrasound findings and patients' subjective symptoms in a larger cohort is warranted. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.
    Ultrasound in Obstetrics and Gynecology 06/2012; · 3.56 Impact Factor
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    Hagit Domev, Michal Amit, Ilana Laevsky, Ayelet Dar, Joseph Itskovitz-Eldor
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    ABSTRACT: Human mesenchymal stem cells (hMSCs) can be derived from various adult and fetal tissues. However, the quality of tissues for the isolation of adult and fetal hMSCs is donor dependent with a nonreproducible yield. In addition, tissue engineering and cell therapy require large-scale production of a pure population of lineage-restricted stem cells that can be easily induced to differentiate into a specific cell type. Therefore, human embryonic stem cells (hESCs) can provide an alternative, plentiful source for generation of reproducible hMSCs. We have developed efficient differentiation protocols for derivation of hMSCs from hESCs, including coculture with murine OP9 stromal cells and feeder layer-free system. Our protocols have resulted in the generation of up to 49% of hMSCs, which expressed CD105, CD90, CD29, and CD44. The hMSCs exhibited high adipogenic, chondrocytic, and osteogenic differentiation in vitro. The latter correlated with osteocalcin secretion and vascular endothelial growth factor (VEGF) production by the differentiating hMSCs. hMSC-derived osteoblasts further differentiated and formed ectopic bone in vivo, and induced the formation of blood vessels in Matrigel implants. Our protocol enables generation of a purified population of hESC-derived MSCs, with the potential of differentiating into several mesodermal lineages, and particularly into vasculogenesis-inducing osteoblasts, which can contribute to the development of bone repair protocols.
    Tissue Engineering Part A 06/2012; · 4.64 Impact Factor
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    ABSTRACT: Pluripotency and proliferative capacity of human embryonic stem cells (hESCs) make them a promising source for basic and applied research as well as in therapeutic medicine. The introduction of human induced pluripotent cells (hiPSCs) holds great promise for patient-tailored regenerative medicine therapies. However, for hESCs and hiPSCs to be applied for therapeutic purposes, long-term genomic stability in culture must be maintained. Until recently, G-banding analysis was considered as the default approach for detecting chromosomal abnormalities in stem cells. Our goal in this study was to apply fluorescence in-situ hybridization (FISH) and comparative genomic hybridization (CGH) for the screening of pluripotent stem cells, which will enable us identifying chromosomal abnormalities in stem cells genome with a better resolution. We studied three hESC lines and two hiPSC lines over long-term culture. Aneuploidy rates were evaluated at different passages, using FISH probes (12,13,16,17,18,21,X,Y). Genomic integrity was shown to be maintained at early passages of hESCs and hiPSCs but, at late passages, we observed low rates mosaiciam in hESCs, which implies a direct correlation between number of passages and increased aneuploidy rate. In addition, CGH analysis revealed a recurrent genomic instability, involving the gain of chromosome 1q. This finding was detected in two unrelated cell lines of different origin and implies that gains of chromosome 1q may endow a clonal advantage in culture. These findings, which could only partially be detected by conventional cytogenetic methods, emphasize the importance of using molecular cytogenetic methods for tracking genomic instability in stem cells.European Journal of Human Genetics advance online publication, 20 June 2012; doi:10.1038/ejhg.2012.128.
    European journal of human genetics: EJHG 06/2012; · 3.56 Impact Factor
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    ABSTRACT: To evaluate the learning curve of senior urogynecologic surgeons performing laparoscopic sacral colpopexy (LSCP) and to assess outcomes and complications of LSCP. We conducted a retrospective study of 47 consecutive women who underwent LSCP for pelvic organ prolapse repair between March 2009 and December 2010 at one tertiary medical center. Preoperative, intraoperative, postoperative, and demographic data were retrieved from patients' electronic charts. Pelvic organ support was assessed objectively using the Pelvic Organ Prolapse Quantification scale (POP-Q). Anatomic failure was determined as POP-Q stage ≥ II. The mean age of patients was 58 years (range 35-73 years). Seven (15 %) who opted to retain their uterus underwent sacrohysteropexies. The median POP-Q was III (II-IV). Of the 47 operations, 96 % (45) were completed by laparoscopy. The duration of surgery decreased as experience of the surgical team increased, from a mean of 196 ± 62 min for the first 15 cases to 162 ± 30 min for the subsequent 30. Four patients (9 %) presented with recurrence of prolapse; three (7 %) had de novo stress urinary incontinence; two sustained a cystotomy during adhesiolysis, and one had a port-site hernia. LSCP is a safe and effective treatment for pelvic organ prolapse, with very few complications. Following the first 15 cases of one surgical team, operative time decreased considerably.
    Archives of Gynecology 05/2012; 286(4):983-8. · 0.91 Impact Factor
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    ABSTRACT: New sources of beta cells are needed in order to develop cell therapies for patients with diabetes. An alternative to forced expansion of post-mitotic beta cells is the induction of differentiation of stem-cell derived progenitor cells that have a natural self-expansion capacity into insulin-producing cells. In order to learn more about these progenitor cells at different stages along the differentiation process in which they become progressively more committed to the final beta cell fate, we took the approach of identifying, isolating and characterizing stage specific progenitor cells. We generated human embryonic stem cell (HESC) clones harboring BAC GFP reporter constructs of SOX17, a definitive endoderm marker, and PDX1, a pancreatic marker, and identified subpopulations of GFP expressing cells. Using this approach, we isolated a highly enriched population of pancreatic progenitor cells from hESCs and examined their gene expression with an emphasis on the expression of stage-specific cell surface markers. We were able to identify novel molecules that are involved in the pancreatic differentiation process, as well as stage-specific cell markers that may serve to define (alone or in combination with other markers) a specific pancreatic progenitor cell. These findings may help in optimizing conditions for ultimately generating and isolating beta cells for transplantation therapy.
    Stem cell reviews 05/2012; 8(3):792-802. · 5.08 Impact Factor

Publication Stats

17k Citations
1,028.97 Total Impact Points

Institutions

  • 1994–2014
    • Technion - Israel Institute of Technology
      • • Ruth and Bruce Rappaport Faculty of Medicine
      • • Rambam Medical Center
      H̱efa, Haifa District, Israel
  • 1970–2014
    • Rambam Medical Center
      • Department of Obstetrics and Gynecology A
      H̱efa, Haifa District, Israel
  • 2013
    • Ministry of Health (Israel)
      Yerushalayim, Jerusalem District, Israel
  • 2007
    • Tel Aviv University
      Tell Afif, Tel Aviv, Israel
  • 2006–2007
    • University of Bonn
      • Institute of Reconstructive Neurobiology
      Bonn, North Rhine-Westphalia, Germany
  • 2004
    • University of Haifa
      H̱efa, Haifa District, Israel
    • Geron Corporation
      Menlo Park, California, United States
  • 2000–2003
    • Hebrew University of Jerusalem
      • Department of Genetics
      Jerusalem, Jerusalem District, Israel
  • 2001
    • Bar Ilan University
      • Faculty of Life Sciences
      Ramat Gan, Tel Aviv, Israel
    • University College London
      • Centre for Neuroendocrinology
      London, ENG, United Kingdom
  • 1999
    • Bnai Zion Medical Center, Haifa
      H̱efa, Haifa District, Israel