Stem Cells Translational Medicine. 2012 May 8; Epub ahead of print.
Specimen Collection for Induced Pluripotent Stem Cell Research: Harmonizing the Approach to Informed Consent.
Lowenthal J, Lipnick S, Rao M, Hull S.
Development of a valve-based cell printer for the formation of human embryonic stem cell spheroid aggregates: In recent years, the use of a simple inkjet technology for cell printing has triggered tremendous interest and established the field of biofabrication. A key challenge has been the development of printing processes which are both controllable and less harmful, in order to preserve cell and tissue viability and functions.
A localized Wnt signal orients asymmetric stem cell division in vitro: Developmental signals such as Wnts are often presented to cells in an oriented manner. To examine the consequences of local Wnt signaling, we immobilized Wnt proteins on beads and introduced them to embryonic stem cells in culture.
Jmjd3 Inhibits Reprogramming by Upregulating Expression of INK4a/Arf and Targeting PHF20 for Ubiquitination: Although somatic cell reprogramming to generate inducible pluripotent stem cells (iPSCs) is associated with profound epigenetic changes, the roles and mechanisms of epigenetic factors in this process remain poorly understood.
Haematopoietic stem cells and early lymphoid progenitors occupy distinct bone marrow niches: Although haematopoietic stem cells (HSCs) are commonly assumed to reside within a specialized microenvironment, or niche, most published experimental manipulations of the HSC niche have affected the function of diverse restricted progenitors. This raises the fundamental question of whether HSCs and restricted progenitors reside within distinct, specialized niches or whether they share a common niche.
Improved ex vivo expansion of adult hematopoietic stem cells by overcoming CUL4- mediated degradation of HOXB4: Direct transduction of the homeobox protein HOXB4 promotes the proliferation of hematopoietic stem cells (HSCs) without induction of leukemogenesis, but requires frequent administration to overcome its short protein half-life (˜1 hour).
Lack of Immune Response to Differentiated Cells Derived from Syngeneic Induced Pluripotent Stem Cells: The prospects for using autologous induced pluripotent stem cells (iPSCs) in cell replacement therapy have been tempered by evidence that undifferentiated, syngeneic mouse iPSCs are immunogenic upon transplantation.
CD271+ Bone Marrow Mesenchymal Stem Cells May Provide a Niche for Dormant Mycobacterium tuberculosis: Mycobacterium tuberculosis (Mtb) can persist in hostile intracellular microenvironments evading immune cells and drug treatment. However, the protective cellular niches where Mtb persists remain unclear.
Direct lineage reprogramming of post-mitotic callosal neurons into corticofugal neurons in vivo: Once programmed to acquire a specific identity and function, cells rarely change in vivo. Neurons of the mammalian central nervous system (CNS) in particular are a classic example of a stable, terminally differentiated cell type. With the exception of the adult neurogenic niches, where a limited set of neuronal subtypes continue to be generated throughout life, CNS neurons are born only during embryonic and early postnatal development.
Reprogramming Adult Schwann Cells to Stem Cell-like Cells by Leprosy Bacilli Promotes Dissemination of Infection: Differentiated cells possess a remarkable genomic plasticity that can be manipulated to reverse or change developmental commitments. Here, we show that the leprosy bacterium hijacks this property to reprogram adult Schwann cells, its preferred host niche, to a stage of progenitor/stem-like cells (pSLC) of mesenchymal trait by downregulating Schwann cell lineage/differentiation-associated genes and upregulating genes mostly of mesoderm development.
Ethical and Policy Issues in the Clinical Translation of Stem Cells: Report of a Focus Session at the ISSCR Tenth Annual Meeting: Alongside the scientific barriers to the clinical translation of stem cell research are ethical and regulatory hurdles. Some of these challenges described by the Ethics and Public Policy Committee at the ISSCR Tenth Annual Meeting are presented here.
Adapting human pluripotent stem cells to high-throughput and high-content screening: The increasing use of human pluripotent stem cells (hPSCs) as a source of cells for drug discovery, cytotoxicity assessment and disease modeling requires their adaptation to large-scale culture conditions and screening formats. Here, we describe a simple and robust protocol for the adaptation of human embryonic stem cells (hESCs) to high-throughput screening (HTS).
Generation of integration-free neural progenitor cells from cells in human urine: Human neural stem cells hold great promise for research and therapy in neural disease. We describe the generation of integration-free and expandable human neural progenitor cells (NPCs).
Autologous mesenchymal stem cell-derived dopaminergic neurons function in parkinsonian macaques: A cell-based therapy for the replacement of dopaminergic neurons has been a long-term goal in Parkinson's disease research. Here, we show that autologous engraftment of A9 dopaminergic neuron-like cells induced from mesenchymal stem cells (MSCs) leads to long-term survival of the cells and restoration of motor function in hemiparkinsonian macaques.
Combined microfabrication and electrospinning to produce 3-D architectures for corneal repair: Corneal stem cell niches are located within the limbus of the eye and are believed to play an important role in corneal regeneration. These niches are often lost in corneal disease or trauma. Our work explores the design of artificial limbal stem cell niches by the fabrication of biodegradable electrospun rings containing bespoke microfeatures.
Trisomy correction in down syndrome induced pluripotent stem cells: Human trisomies can alter cellular phenotypes and produce congenital abnormalities such as Down syndrome (DS). Here we have generated induced pluripotent stem cells (iPSCs) from DS fibroblasts and introduced a TKNEO transgene into one copy of chromosome 21 by gene targeting.
Somatic copy number mosaicism in human skin revealed by induced pluripotent stem cells: Reprogramming somatic cells into induced pluripotent stem cells (iPSCs) has been suspected of causing de novo copy number variation. To explore this issue, here we perform a whole-genome and transcriptome analysis of 20 human iPSC lines derived from the primary skin fibroblasts of seven individuals using next-generation sequencing.
Towards germline gene therapy of inherited mitochondrial diseases: Mutations in mitochondrial DNA (mtDNA) are associated with severe human diseases and are maternally inherited through the egg’s cytoplasm. Here we investigated the feasibility of mtDNA replacement in human oocytes by spindle transfer (ST; also called spindle–chromosomal complex transfer).
Comparison of Allogeneic vs Autologous Bone Marrow–Derived Mesenchymal Stem Cells Delivered by Transendocardial Injection in Patients With Ischemic Cardiomyopathy. The POSEIDON Randomized Trial: CONTEXT Mesenchymal stem cells (MSCs) are under evaluation as a therapy for ischemic cardiomyopathy (ICM). Both autologous and allogeneic MSC therapies are possible; however, their safety and efficacy have not been compared.
Dedifferentiation of Neurons and Astrocytes by Oncogenes Can Induce Gliomas in Mice: Glioblastoma multiforme (GBM) is the most common and aggressive malignant primary brain tumor in humans. Here we show that gliomas can originate from differentiated cells in the central nervous system (CNS), including cortical neurons.
Towards germline gene therapy of inherited mitochondrial diseases: Mutations in mitochondrial DNA (mtDNA) are associated with severe human diseases and are maternally inherited through the egg's cytoplasm. Here we investigated the feasibility of mtDNA replacement in human oocytes by spindle transfer (ST; also called spindle-chromosomal complex transfer).
Self-renewal of embryonic-stem-cell-derived progenitors by organ-matched mesenchyme: One goal of regenerative medicine, to use stem cells to replace cells lost by injury or disease, depends on producing an excess of the relevant cell for study or transplantation. To this end, the stepwise differentiation of stem cells into specialized derivatives has been successful for some cell types, but a major problem remains the inefficient conversion of cells from one stage of differentiation to the next. If specialized cells are to be produced in large numbers it will be necessary to expand progenitor cells, without differentiation, at some steps of the process.
Long-term safety and efficacy of human induced pluripotent stem cell (iPS) grafts in a preclinical model of retinitis pigmentosa: The Food and Drug Administration has recently approved phase I/II clinical trials for ES cell-based retinal pigmented epithelium (RPE) transplantation, but this allograft transplantation requires life-long immunosuppressive therapy. Autografts from patient-specific induced pluripotent stem (iPS) cells offer an alternative solution to this problem. However, more data is required to establish the safety and efficacy of iPS transplantation in animal models before moving iPS therapy into clinical trials.
Offspring from Oocytes Derived from in Vitro Primordial Germ Cell-Like Cells in Mice: Reconstitution of female germ-cell development in vitro is a key challenge in reproductive biology and medicine. We show here that female (XX) embryonic stem cells and induced pluripotent stem cells in mice are induced into primordial germ cell-like cells (PGCLCs), which, when aggregated with female gonadal somatic cells as reconstituted ovaries, undergo X-reactivation, imprint erasure, cyst formation, and exhibit meiotic potential.
Restoration of auditory evoked responses by human ES-cell-derived otic progenitors: Deafness is a condition with a high prevalence worldwide, produced primarily by the loss of the sensory hair cells and their associated spiral ganglion neurons (SGNs). Of all the forms of deafness, auditory neuropathy is of particular concern. This condition, defined primarily by damage to the SGNs with relative preservation of the hair cells, is responsible for a substantial proportion of patients with hearing impairment. Although the loss of hair cells can be circumvented partially by a cochlear implant, no routine treatment is available for sensory neuron loss, as poor innervation limits the prospective performance of an implant.
Direct Reprogramming of Fibroblasts into Embryonic Sertoli-like Cells by Defined Factors: Sertoli cells are considered the "supporting cells" of the testis that play an essential role in sex determination during embryogenesis and in spermatogenesis during adulthood. Their essential roles in male fertility along with their immunosuppressive and neurotrophic properties make them an attractive cell type for therapeutic applications.
Gene therapy for adenosine deaminase-deficient severe combined immune deficiency: clinical comparison of retroviral vectors and treatment plans: We conducted a gene therapy trial in 10 patients with adenosine deaminase-deficient severe combined immunodeficiency (ADA-deficient SCID) using two slightly different retroviral vectors for the transduction of patients' bone marrow CD34+ cells.
Long-Distance Growth and Connectivity of Neural Stem Cells after Severe Spinal Cord Injury: Neural stem cells (NSCs) expressing GFP were embedded into fibrin matrices containing growth factor cocktails and grafted to sites of severe spinal cord injury. Grafted cells differentiated into multiple cellular phenotypes, including neurons, which extended large numbers of axons over remarkable distances. Extending axons formed abundant synapses with host cells.
Human ES-cell-derived cardiomyocytes electrically couple and suppress arrhythmias in injured hearts: Transplantation studies in mice and rats have shown that human embryonic-stem-cell-derived cardiomyocytes (hESC-CMs) can improve the function of infarcted hearts, but two critical issues related to their electrophysiological behaviour in vivo remain unresolved. First, the risk of arrhythmias following hESC-CM transplantation in injured hearts has not been determined. Second, the electromechanical integration of hESC-CMs in injured hearts has not been demonstrated, so it is unclear whether these cells improve contractile function directly through addition of new force-generating units.
Regulation of Embryonic and Induced Pluripotency by Aurora Kinase-p53 Signaling: Many signals must be integrated to maintain self-renewal and pluripotency in embryonic stem cells (ESCs) and to enable induced pluripotent stem cell (iPSC) reprogramming. However, the exact molecular regulatory mechanisms remain elusive. To unravel the essential internal and external signals required for sustaining the ESC state, we conducted a short hairpin (sh) RNA screen of 104 ESC-associated phosphoregulators.
Growth Factor-Activated Stem Cell Circuits and Stromal Signals Cooperatively Accelerate Non-Integrated iPSC Reprogramming of Human Myeloid Progenitors: Nonviral conversion of skin or blood cells into clinically useful human induced pluripotent stem cells (hiPSC) occurs in only rare fractions (~0.001%-0.5%) of donor cells transfected with non-integrating reprogramming factors. Pluripotency induction of developmentally immature stem-progenitors is generally more efficient than differentiated somatic cell targets. However, the nature of augmented progenitor reprogramming remains obscure, and its potential has not been fully explored for improving the extremely slow pace of non-integrated reprogramming.
A restricted cell population propagates glioblastoma growth after chemotherapy: Glioblastoma multiforme is the most common primary malignant brain tumour, with a median survival of about one year. This poor prognosis is due to therapeutic resistance and tumour recurrence after surgical removal. Precisely how recurrence occurs is unknown.
Derivation conditions impact x-inactivation status in female human induced pluripotent stem cells: Female human induced pluripotent stem cell (hiPSC) lines exhibit variability in X-inactivation status. The majority of hiPSC lines maintain one transcriptionally active X (Xa) and one inactive X (Xi) chromosome from donor cells. However, at low frequency, hiPSC lines with two Xas are produced, suggesting that epigenetic alterations of the Xi occur sporadically during reprogramming.
Pharmacological Rescue of Mitochondrial Deficits in iPSC-Derived Neural Cells from Patients with Familial Parkinson's Disease: Parkinson's disease (PD) is a common neurodegenerative disorder caused by genetic and environmental factors that results in degeneration of the nigrostriatal dopaminergic pathway in the brain. We analyzed neural cells generated from induced pluripotent stem cells (iPSCs) derived from PD patients and presymptomatic individuals carrying mutations in the PINK1 (PTEN-induced putative kinase 1) and LRRK2 (leucine-rich repeat kinase 2) genes, and compared them to those of healthy control subjects.
Stem Cell Therapy for Craniofacial Bone Regeneration: A Randomized, Controlled, Feasibility Trial: Background: Stem cell therapy offers potential in the regeneration of craniofacial bone defects however, has it not been studied clinically. Tissue repair cells (TRCs) isolated from bone marrow represent a mixed stem and progenitor population enriched in CD90 and CD14 positive cells. In this Phase I/II, randomized, controlled, feasibility trial, we investigated TRC cell therapy to reconstruct localized craniofacial bone defects.
Valproic Acid Confers Functional Pluripotency to Human Amniotic Fluid Stem Cells in a Transgene-free Approach: Induced pluripotent stem cells (iPSCs) with potential for therapeutic applications can be derived from somatic cells via ectopic expression of a set of limited and defined transcription factors. However, due to risks of random integration of the reprogramming transgenes into the host genome, the low efficiency of the process, and the potential risk of virally induced tumorigenicity, alternative methods have been developed to generate pluripotent cells using nonintegrating systems, albeit with limited success.
Embryonic stem cell potency fluctuates with endogenous retrovirus activity: Embryonic stem (ES) cells are derived from blastocyst-stage embryos and are thought to be functionally equivalent to the inner cell mass, which lacks the ability to produce all extraembryonic tissues. Here we identify a rare transient cell population within mouse ES and induced pluripotent stem (iPS) cell cultures that expresses high levels of transcripts found in two-cell (2C) embryos in which the blastomeres are totipotent.
Induced Pluripotent Stem Cells from Patients with Huntington's Disease Show CAG-Repeat-Expansion-Associated Phenotypes: Huntington's disease (HD) is an inherited neurodegenerative disorder caused by an expanded stretch of CAG trinucleotide repeats that results in neuronal dysfunction and death. Here, The HD Consortium reports the generation and characterization of 14 induced pluripotent stem cell (iPSC) lines from HD patients and controls.
Genetic Correction of Huntington’s Disease Phenotypes in Induced Pluripotent Stem Cells: Huntington's disease (HD) is caused by a CAG expansion in the huntingtin gene. Expansion of the polyglutamine tract in the huntingtin protein results in massive cell death in the striatum of HD patients. We report that human induced pluripotent stem cells (iPSCs) derived from HD patient fibroblasts can be corrected by the replacement of the expanded CAG repeat with a normal repeat using homologous recombination, and that the correction persists in iPSC differentiation into DARPP-32-positive neurons in vitro and in vivo.
Direct Reprogramming of Mouse and Human Fibroblasts into Multipotent Neural Stem Cells with a Single Factor: The generation of induced pluripotent stem cells (iPSCs) and induced neuronal cells (iNCs) from somatic cells provides new avenues for basic research and potential transplantation therapies for neurological diseases. However, clinical applications must consider the risk of tumor formation by iPSCs and the inability of iNCs to self-renew in culture.
Differentiation of multipotent vascular stem cells contributes to vascular diseases: It is generally accepted that the de-differentiation of smooth muscle cells, from the contractile to the proliferative/synthetic phenotype, has an important role during vascular remodelling and diseases. Here we provide evidence that challenges this theory.
Engineering bone tissue from human embryonic stem cells: In extensive bone defects, tissue damage and hypoxia lead to cell death, resulting in slow and incomplete healing. Human embryonic stem cells (hESC) can give rise to all specialized lineages found in healthy bone and are therefore uniquely suited to aid regeneration of damaged bone. We show that the cultivation of hESC-derived mesenchymal progenitors on 3D osteoconductive scaffolds in bioreactors with medium perfusion leads to the formation of large and compact bone constructs.
Robust cardiomyocyte differentiation from human pluripotent stem cells via temporal modulation of canonical Wnt signaling: Human pluripotent stem cells (hPSCs) offer the potential to generate large numbers of functional cardiomyocytes from clonal and patient-specific cell sources. Here we show that temporal modulation of Wnt signaling is both essential and sufficient for efficient cardiac induction in hPSCs under defined, growth factor-free conditions.
Derivation and cardiomyocyte differentiation of induced pluripotent stem cells from heart failure patients: Myocardial cell replacement therapies are hampered by a paucity of sources for human cardiomyocytes and by the expected immune rejection of allogeneic cell grafts. The ability to derive patient-specific human-induced pluripotent stem cells (hiPSCs) may provide a solution to these challenges.
Heart repair by reprogramming non-myocytes with cardiac transcription factors: The adult mammalian heart possesses little regenerative potential following injury. Fibrosis due to activation of cardiac fibroblasts impedes cardiac regeneration and contributes to loss of contractile function, pathological remodelling and susceptibility to arrhythmias. Cardiac fibroblasts account for a majority of cells in the heart and represent a potential cellular source for restoration of cardiac function following injury through phenotypic reprogramming to a myocardial cell fate.
A Stem Cell–Based Approach to Cartilage Repair: Osteoarthritis (OA) is a degenerative joint disease that involves the destruction of articular cartilage and eventually leads to disability. Molecules that promote the selective differentiation of multipotent mesenchymal stem cells (MSCs) into chondrocytes may stimulate the repair of damaged cartilage.
Self-renewing endodermal progenitor lines generated from human pluripotent stem cells: The use of human pluripotent stem cells for laboratory studies and cell-based therapies is hampered by their tumor-forming potential and limited ability to generate pure populations of differentiated cell types in vitro. To address these issues, we established endodermal progenitor (EP) cell lines from human embryonic and induced pluripotent stem cells. Optimized growth conditions were established that allow near unlimited (>10(16)) EP cell self-renewal in which they display a morphology and gene expression pattern characteristic of definitive endoderm.
Generation of Multipotent Lung and Airway Progenitors from Mouse ESCs and Patient-Specific Cystic Fibrosis iPSCs:Deriving lung progenitors from patient-specific pluripotent cells is a key step in producing differentiated lung epithelium for disease modeling and transplantation. By mimicking the signaling events that occur during mouse lung development, we generated murine lung progenitors in a series of discrete steps.
MicroRNA-Mediated In Vitro and In Vivo Direct Reprogramming of Cardiac Fibroblasts to Cardiomyocytes:Rationale: Repopulation of the injured heart with new, functional cardiomyocytes remains a daunting challenge for cardiac regenerative medicine. An ideal therapeutic approach would involve an effective method at achieving direct conversion of injured areas to functional tissue in situ.
In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes: The reprogramming of adult cells into pluripotent cells or directly into alternative adult cell types holds great promise for regenerative medicine. We reported previously that cardiac fibroblasts, which represent 50% of the cells in the mammalian heart, can be directly reprogrammed to adult cardiomyocyte-like cells in vitro by the addition of Gata4, Mef2c and Tbx5 (GMT).
A Stem Cell-Based Approach to Cartilage Repair: Osteoarthritis (OA) is a degenerative joint disease that involves destruction of articular cartilage and eventually leads to disability. Molecules that promote the selective differentiation of multipotent mesenchymal stem cells (MSCs) into chondrocytes may stimulate the repair of damaged cartilage.
Human Embryonic Stem Cell-Derived GABA Neurons Correct Locomotion Deficits in Quinolinic Acid-Lesioned Mice:Degeneration of medium spiny GABA neurons in the basal ganglia underlies motor dysfunction inHuntington’s disease (HD), which presently lacks effective therapy. ding to correction of motor deficits. This finding raises hopes for cell therapy for HD. Cell Stem Cell [Epub ahead of print]; laboratory of S.-C. Zhang (NIH-supported). 2012 Mar 15.
Lumbar Intraspinal Injection of Neural Stem Cells in Patients with ALS: Results of a Phase I Trial in 12 Patients: Advances in stem cell biology have generated intense interest in the prospect of transplanting stem cells into the nervous system for the treatment of neurodegenerative diseases.
Signaling Network Crosstalk in Human Pluripotent Cells: A Smad2/3-Regulated Switch that Controls the Balance between Self-Renewal and Differentiation: A general mechanism for how intracellular signaling pathways in human pluripotent cells are coordinated and how they maintain self-renewal remain to be elucidated.
Chimerism and Tolerance Without GVHD or Engraftment Syndrome in HLA-Mismatched Combined Kidney and Hematopoietic Stem Cell Transplantation: The toxicity of chronic immunosuppressive agents required for organ transplant maintenance has prompted investigators to pursue approaches to induce immune tolerance. We developed an approach using a bioengineered mobilized cellular product enriched for hematopoietic stem cells (HSCs) and tolerogenic graft facilitating cells (FCs) combined with nonmyeloablative conditioning; this approach resulted in engraftment, durable chimerism, and tolerance induction in recipients with highly mismatched related and unrelated donors.
Wild-type microglia arrest pathology in a mouse model of Rett syndrome: Rett syndrome is an X-linked autism spectrum disorder. The disease is characterized in most cases by mutation of the MECP2 gene, which encodes a methyl-CpG-binding protein. Although MECP2 is expressed in many tissues, the disease is generally attributed to a primary neuronal dysfunction.
Probing sporadic and familial Alzheimer's disease using induced pluripotent stem cells: Our understanding of Alzheimer's disease pathogenesis is currently limited by difficulties in obtaining live neurons from patients and the inability to model the sporadic form of the disease. It may be possible to overcome these challenges by reprogramming primary cells from patients into induced pluripotent stem cells (iPSCs).
Oocyte formation by mitotically active germ cells purified from ovaries of reproductive-age women: Germline stem cells that produce oocytes in vitro and fertilization-competent eggs in vivo have been identified in and isolated from adult mouse ovaries.
Young Dentate Granule Cells Mediate Pattern Separation, whereas Old Granule Cells Facilitate Pattern Completion: Adult-born granule cells (GCs), a minor population of cells in the hippocampal dentate gyrus, are highly active during the first few weeks after functional integration into the neuronal network, distinguishing them from less active, older adult-born GCs and the major population of dentate GCs generated developmentally.
Rapid expansion of human hematopoietic stem cells by automated control of inhibitory feedback signaling: Clinical hematopoietic transplantation outcomes are strongly correlated with the numbers of cells infused. Anticipated novel therapeutic implementations of hematopoietic stem cells (HSCs) and their derivatives further increase interest in strategies to expand HSCs ex vivo.
Bone marrow homing and engraftment of human hematopoietic stem and progenitor cells is mediated by a polarized membrane domain: Manipulation of hematopoietic stem/progenitor cells (HSPC) ex vivo is of clinical importance for stem cell expansion and gene therapy applications. However, most cultured HSPC are actively cycling and show a homing and engraftment defect compared with the predominantly quiescent non-cultured HSPC.
Adult Human RPE Can Be Activated into a Multipotent Stem Cell that Produces Mesenchymal Derivatives: The retinal pigment epithelium (RPE) is a monolayer of cells underlying and supporting the neural retina. It begins as a plastic tissue, capable, in some species, of generating lens and retina, but differentiates early in development and remains normally nonproliferative throughout life.
Generation of Chimeric Rhesus Monkeys: Totipotent cells in early embryos are progenitors of all stem cells and are capable of developing into a whole organism, including extraembryonic tissues such as placenta. Pluripotent cells in the inner cell mass (ICM) are the descendants of totipotent cells and can differentiate into any cell type of a body except extraembryonic tissues.
Embryonic stem cell trials for macular degeneration: a preliminary report: It has been 13 years since the discovery of human embryonic stem cells (hESCs). Our report provides the first description of hESC-derived cells transplanted into human patients.
Reprogramming factor stoichiometry influences the epigenetic state and biological properties of induced pluripotent stem cells: We compared two genetically highly defined transgenic systems to identify parameters affecting reprogramming of somatic cells to a pluripotent state.
Interactions between cancer stem cells and their niche govern metastatic colonization: Metastatic growth in distant organs is the major cause of cancer mortality. The development of metastasis is a multistage process with several rate-limiting steps.
Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson's disease: Human pluripotent stem cells (PSCs) are a promising source of cells for applications in regenerative medicine. Directed differentiation of PSCs into specialized cells such as spinal motoneurons or midbrain dopamine (DA) neurons has been achieved.
Human embryonic stem cell-derived neurons adopt and regulate the activity of an established neural network: Whether hESC-derived neurons can fully integrate with and functionally regulate an existing neural network remains unknown.
Using iPSC-derived neurons to uncover cellular phenotypes associated with Timothy syndrome: Monogenic neurodevelopmental disorders provide key insights into the pathogenesis of disease and help us understand how specific genes control the development of the human brain.
Functional integration of dopaminergic neurons directly converted from mouse fibroblasts: Recent advances in somatic cell reprogramming have highlighted the plasticity of the somatic epigenome, particularly through demonstrations of direct lineage reprogramming of one somatic cell type to another by defined factors.
Targeted gene correction of a1-antitrypsin deficiency in induced pluripotent stem cells: Human induced pluripotent stem cells (iPSCs) represent a unique opportunity for regenerative medicine because they offer the prospect of generating unlimited quantities of cells for autologous transplantation, with potential application in treatments for a broad range of disorders.
Distal Airway Stem Cells Yield Alveoli In Vitro and during Lung Regeneration following H1N1 Influenza Infection: The extent of lung regeneration following catastrophic damage and the potential role of adult stem cells in such a process remains obscure.
Tracking single hematopoietic stem cells in vivo using high-throughput sequencing in conjunction with viral genetic barcoding: Disentangling cellular heterogeneity is a challenge in many fields, particularly in the stem cell and cancer biology fields.
Sox2(+) adult stem and progenitor cells are important for tissue regeneration and survival of mice: The transcription factor Sox2 maintains the pluripotency of early embryonic cells and regulates the formation of several epithelia during fetal development.
An alternative splicing switch regulates embryonic stem cell pluripotency and reprogramming: Alternative splicing (AS) is a key process underlying the expansion of proteomic diversity and the regulation of gene expression.
Modeling familial Alzheimer’s disease with induced pluripotent stem cells: Alzheimer’s disease (AD) is the most common form of age-related dementia, characterized by progressive memory loss and cognitive disturbance.
Human oocytes reprogram somatic cells to a pluripotent state: The exchange of the oocyte's genome with the genome of a somatic cell, followed by the derivation of pluripotent stem cells, could enable the generation of specific cells affected in degenerative human diseases.
Conversion of Mouse and Human Fibroblasts into Functional Spinal Motor Neurons: The mammalian nervous system comprises many distinct neuronal subtypes, each with its own phenotype and differential sensitivity to degenerative disease.
Reconstitution of the Mouse Germ Cell Specification Pathway in Culture by Pluripotent Stem Cells: The generation of properly functioning gametes in vitro requires reconstitution of the multistepped pathway of germ cell development.
An antibody against SSEA-5 glycan on human pluripotent stem cells enables removal of teratoma-forming cells: An important risk in the clinical application of human pluripotent stem cells (hPSCs), including human embryonic and induced pluripotent stem cells (hESCs and hiPSCs), is teratoma formation by residual undifferentiated cells.
Direct generation of functional dopaminergic neurons from mouse and human fibroblasts: Transplantation of dopaminergic neurons can potentially improve the clinical outcome of Parkinson's disease, a neurological disorder resulting from degeneration of mesencephalic dopaminergic neurons.
Induction of human neuronal cells by defined transcription factors: Somatic cell nuclear transfer, cell fusion, or expression of lineage-specific factors have been shown to induce cell-fate changes in diverse somatic cell types.
Cell fate potential of human pluripotent stem cells is encoded by histone modifications: Human embryonic stem cells (hESCs) expressing pluripotency markers are assumed to possess equipotent developmental potential.
Generation of isogenic pluripotent stem cells differing exclusively at two early onset Parkinson point mutations: Patient-specific induced pluripotent stem cells (iPSCs) derived from somatic cells provide a unique tool for the study of human disease, as well as a promising source for cell replacement therapies.
Epigenetic memory and preferential lineage-specific differentiation in induced pluripotent stem cells derived from human pancreatic islet Beta cells: Human induced pluripotent stem cells (HiPSCs) appear to be highly similar to human embryonic stem cells (HESCs).
Direct Reprogramming of Adult Human Fibroblasts to Functional Neurons under Defined Conditions: Human induced pluripotent stem cells (hiPSCs) have been generated by reprogramming a number of different somatic cell types using a variety of approaches.
Optic Vesicle-like Structures Derived from Human Pluripotent Stem Cells Facilitate a Customized Approach to Retinal Disease Treatment: Differentiation methods for human induced pluripotent stem cells (hiPSCs) typically yield progeny from multiple tissue lineages, limiting their utility for drug testing and autologous cell transplantation.
Reprogramming of Mouse and Human Cells to Pluripotency Using Mature MicroRNAs: Induced pluripotent stem cells (iPSCs) can be generated from differentiated human and mouse somatic cells using transcription factors such as Oct4, Sox2, Klf4, and c-Myc.
Direct reprogramming of somatic cells is promoted by maternal transcription factor Glis1: Induced pluripotent stem cells (iPSCs) are generated from somatic cells by the transgenic expression of three transcription factors collectively called OSK: Oct3/4 (also called Pou5f1), Sox2 and Klf4.
De novo cardiomyocytes from within the activated adult heart after injury: A significant bottleneck in cardiovascular regenerative medicine is the identification of a viable source of stem/progenitor cells that could contribute new muscle after ischaemic heart disease and acute myocardial infarction.
Specification of transplantable astroglial subtypes from human pluripotent stem cells: Human pluripotent stem cells (hPSCs) have been differentiated efficiently to neuronal cell types. However, directed differentiation of hPSCs to astrocytes and astroglial subtypes remains elusive.
Immunogenicity of induced pluripotent stem cells: Induced pluripotent stem cells (iPSCs), reprogrammed from somatic cells with defined factors, hold great promise for regenerative medicine as the renewable source of autologous cells.
Targeted Gene Correction of Laminopathy-Associated LMNA Mutations in Patient-Specific iPSCs: Combination of stem cell-based approaches with gene-editing technologies represents an attractive strategy for studying human disease and developing therapies.
Induction of human neuronal cells by defined transcription factors: Somatic cell nuclear transfer, cell fusion, or expression of lineage-specific factors have been shown to induce cell-fate changes in diverse somatic cell types.
Using induced pluripotent stem cells to investigate cardiac phenotypes in Timothy syndrome: Individuals with congenital or acquired prolongation of the QT interval, or long QT syndrome (LQTS), are at risk of life-threatening ventricular arrhythmia.
Highly Efficient miRNA-Mediated Reprogramming of Mouse and Human Somatic Cells to Pluripotency: Transcription factor-based cellular reprogramming has opened the way to converting somatic cells toa pluripotent state, but has faced limitations resulting from the requirement for transcription factors and the relative inefficiency of the process.
Modelling schizophrenia using human induced pluripotent stem cells: Schizophrenia (SCZD) is a debilitating neurological disorder with a world-wide prevalence of 1%; there is a strong genetic component, with an estimated heritability of 80-85%.
Genetic correction and analysis of induced pluripotent stem cells from a patient with gyrate atrophy: Gene-corrected patient-specific induced pluripotent stem (iPS) cells offer a unique approach to gene therapy.
The Controlled Generation of Functional Basal Forebrain Cholinergic Neurons from Human Embryonic Stem Cells: An early substantial loss of basal forebrain cholinergic neurons [BFCN] is a constant feature of Alzheimer's disease and is associated with deficits in spatial learning and memory.
A bioinformatic assay for pluripotency in human cells: Pluripotent stem cells (PSCs) are defined by their potential to generate all cell types of an organism.
Copy number variation and selection during reprogramming to pluripotency: The mechanisms underlying the low efficiency of reprogramming somatic cells into induced pluripotent stem (iPS) cells are poorly understood.
Self-renewal induced efficiently, safely, and effective therapeutically with one regulatable gene in a human somatic progenitor cell: In the field of induced potency and fate reprogramming, it remains unclear what the best starting cell might be and to what extent a cell need be transported back to a more primitive state for translational purposes.
Somatic coding mutations in human induced pluripotent stem cells: Defined transcription factors can induce epigenetic reprogramming of adult mammalian cells into induced pluripotent stem cells.
Efficient human iPS cell derivation by a non-integrating plasmid from blood cells with unique epigenetic and gene expression signatures: To identify accessible and permissive human cell types for efficient derivation of induced pluripotent stem cells (iPSCs), we investigated epigenetic and gene expression signatures of multiple postnatal cell types such as fibroblasts and blood cells.
Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells: Induced pluripotent stem cells (iPSCs) offer immense potential for regenerative medicine and studies of disease and development.
Reference Maps of Human ES and iPS Cell Variation Enable High-Throughput Characterization of Pluripotent Cell Lines: The developmental potential of human pluripotent stem cells suggests that they can produce disease-relevant cell types for biomedical research.
Dynamic Changes in the Copy Number of Pluripotency and Cell Proliferation Genes in Human ESCs and iPSCs during Reprogramming and Time in Culture: Genomic stability is critical for the clinical use of human embryonic and induced pluripotent stem cells.
Equivalence of Conventionally-Derived and Parthenote-Derived Human Embryonic Stem Cells: As human embryonic stem cell (hESC) lines can be derived via multiple means, it is important to determine particular characteristics of individual lines that may dictate the applications to which they are best suited.
Evidence for the cure of HIV infection by CCR5Δ32/Δ32 stem cell transplantation: HIV entry into CD4(+) cells requires interaction with a cellular receptor, generally either CCR5 or CXCR4.
Maternal T cells limit engraftment after in utero hematopoietic cell transplantation in mice: Transplantation of allogeneic stem cells into the early gestational fetus, a treatment termed in utero hematopoietic cell transplantation (IUHCTx), could potentially overcome the limitations of bone marrow transplants, including graft rejection and the chronic immunosuppression required to prevent rejection.
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