Time filter

Source Type

New York City, NY, United States

Yodmuang S.,Columbia University | Marolt D.,The New York Stem Cell Foundation Research Institute | Marcos-Campos I.,Columbia University | Gadjanski I.,University of Belgrade | Vunjak-Novakovic G.,Columbia University
Stem Cell Reviews and Reports | Year: 2015

Derivation of articular chondrocytes from human stem cells would advance our current understanding of chondrogenesis, and accelerate development of new stem cell therapies for cartilage repair. Chondrogenic differentiation of human embryonic stem cells (hESCs) has been studied using supplemental and cell-secreted morphogenetic factors. The use of bioreactors enabled insights into the effects of physical forces and controlled oxygen tension. In this study, we investigated the interactive effects of controlled variation of oxygen tension and chondrocyte-secreted morphogenetic factors on chondrogenic differentiation of hESCs in the embryoid body format (hESC-EB). Transient hypoxic culture (2 weeks at 5 % O2 followed by 1 week at 21 % O2) of hESC-EBs in medium conditioned with primary chondrocytes up-regulated the expression of SOX9 and suppressed pluripotent markers OCT4 and NANOG. Pellets derived from these cells showed significant up-regulation of chondrogenic genes (SOX9, COL2A1, ACAN) and enhanced production of cartilaginous matrix (collagen type II and proteoglycan) as compared to the pellets from hESC-EBs cultured under normoxic conditions. Gene expression profiles corresponded to those associated with native cartilage development, with early expression of N-cadherin (indicator of cell condensation) and late expression of aggrecan (ACAN, indicator of proteoglycan production). When implanted into highly vascularized subcutaneous area in immunocompromised mice for 4 weeks, pellets remained phenotypically stable and consisted of cartilaginous extracellular matrix (ECM), without evidence of dedifferentiation or teratoma formation. Based on these results, we propose that chondrogenesis in hESC can be synergistically enhanced by a control of oxygen tension and morphogenetic factors secreted by chondrocytes. © 2015, Springer Science+Business Media New York. Source

Kaewkhaw R.,U.S. National Institutes of Health | Kaewkhaw R.,Mahidol University | Swaroop M.,U.S. National Institutes of Health | Homma K.,U.S. National Institutes of Health | And 13 more authors.
Investigative Ophthalmology and Visual Science | Year: 2016

We discuss the use of pluripotent stem cell lines carrying fluorescent reporters driven by retinal promoters to derive three-dimensional (3-D) retina in culture and how this system can be exploited for elucidating human retinal biology, creating disease models in a dish, and designing targeted drug screens for retinal and macular degeneration. Furthermore, we realize that stem cell investigations are labor-intensive and require extensive resources. To expedite scientific discovery by sharing of resources and to avoid duplication of efforts, we propose the formation of a Retinal Stem Cell Consortium. In the field of vision, such collaborative approaches have been enormously successful in elucidating genetic susceptibility associated with age-related macular degeneration. © 2016, Association for Research in Vision and Ophthalmology Inc. All rights reserved. Source

News Article
Site: http://news.yahoo.com/science/

NEW YORK (Reuters) - Scientists for the first time have generated a type of embryonic stem cell that carries a single copy of the human genome rather than the usual two, a development that could advance research in gene editing, genetic screening and regenerative medicine. Derived from a female egg, the stem cells are the first human cells known to be capable of cell division with just one copy of the parent cell's genome, according to a study appearing on Wednesday in the journal Nature. The breakthrough is expected to reduce the complexity of identifying genetic abnormalities, which in turn could advance understanding of many diseases, researchers said. Human cells are considered diploid because they inherit two sets of chromosomes, 23 from the mother and 23 from the father. Reproductive egg and sperm cells are known as haploid because they contain a single set of chromosomes. They cannot divide to make more eggs and sperm. "What is fundamentally new is we have cells that can divide and renew with a single genome. That is just unprecedented," said Dieter Egli of Columbia University Medical Center in New York, co-author of the study with Dr. Nissim Benvenisty of The Hebrew University of Jerusalem. The researchers, including scientists from The New York Stem Cell Foundation Research Institute, found the haploid stem cells capable of differentiating into many other cell types, such as nerve, heart, and pancreatic cells, while retaining a single set of chromosomes. Sequencing of the human genome has yielded a wealth of new information about myriad genetic variations and how they interact with each other. But isolating and understanding specific gene abnormalities is challenging with diploid cells because they typically have a copy that is normal and serves as a backup. "We have two genes of everything and if one is mutated the effect is not so obvious," said Egli in a telephone interview while vacationing in the French Alps. "Because these cells reduce the number of possible combinations and reduce the number of variance, it should be easier to get the answers." A next logical step in the research, Egli said, is to modify these haploid stem cells either to introduce new disease variances or correct those that are already there. "That should give us a way to better understand those many, many variances that are being identified in genome sequencing efforts that we think have something to do with disease."

Woodard C.M.,The New York Stem Cell Foundation Research Institute | Campos B.A.,The New York Stem Cell Foundation Research Institute | Kuo S.-H.,Columbia University | Nirenberg M.J.,New York University | And 21 more authors.
Cell Reports | Year: 2014

Parkinson's disease (PD) has been attributed to a combination of genetic and nongenetic factors. We studied a set of monozygotic twins harboring the heterozygous glucocerebrosidase mutation (GBA N370S) but clinically discordant for PD. We applied induced pluripotent stem cell (iPSC) technology forPD disease modeling using the twins' fibroblaststo evaluate and dissect the genetic and nongenetic contributions. Utilizing fluorescence-activated cell sorting, we obtained a homogenous population of"footprint-free" iPSC-derived midbrain dopaminergic (mDA) neurons. The mDA neurons from both twins had ~50% GBA enzymatic activity,~3-fold elevated α-synuclein protein levels, andareduced capacity to synthesize and release dopamine. Interestingly, the affected twin's neurons showed an even lower dopamine level, increased monoamineoxidase B (MAO-B) expression, and impaired intrinsic network activity. Overexpression of wild-type GBA and treatment with MAO-B inhibitors normalized α-synuclein and dopamine levels, suggesting a combination therapy for the affected twin. © 2014 The Authors. Source

Yamada M.,The New York Stem Cell Foundation Research Institute | Egli D.,The New York Stem Cell Foundation Research Institute | Egli D.,Columbia University
Current Opinion in Genetics and Development | Year: 2015

Nuclear transfer has seen a remarkable comeback in the past few years. Three groups have independently reported the derivation of stem cell lines by somatic cell nuclear transfer, from either adult, neonatal or fetal cells. Though the ability of human oocytes to reprogram somatic cells to stem cells had long been anticipated, success did not arrive on a straightforward path. Little was known about human oocyte biology, and nuclear transfer protocols developed in animals required key changes to become effective with human eggs. By overcoming these challenges, human nuclear transfer research has contributed to a greater understanding of oocyte biology, provided a point of reference for the comparison of induced pluripotent stem cells, and delivered a method for the generation of personalized stem cells with therapeutic potential. © 2015 Elsevier Ltd. Source

Discover hidden collaborations