Abstract:
:Pluripotent stem cell-derived endothelial cells (ECs) have great potential to be used in vascular therapy or tissue engineering. It is also much desired to obtain arterial or venous ECs for specific applications. Factors that are critical for the proper arterial or venous differentiation from pluripotent stem cells still need to be understood. Here, we aim at investigating this problem deeper by examining neuropilin-1 (Nrp1), an early arterial marker that may be critical for arterial cell fate commitment. Using murine embryonic stem cells as the model system, this study investigates the neuropilin-1 (Nrp1) expression during the differentiation of pluripotent stem cells toward a vascular progenitor population. We hypothesize that Nrp1, an early arterial marker present in a developing embryo, may be more responsive when further induced in vitro toward an arterial fate. We developed a two-step differentiation approach that yielded a large percentage of Nrp1+ vascular progenitor cells (VPCs) and investigated their potential to become arterial ECs. We have defined the culture parameters that contribute greatly to the emergence of Nrp1+ VPCs: certain soluble factors, especially Wnt and BMP4, early cell-cell contact, and hypoxia. Subsequent isolation of this population demonstrated a highly proliferative and network-forming behavior. The Nrp1+ VPCs exhibited increased gene expression of several Notch pathway-related arterial markers compared with Nrp1- VPCs. Most importantly, Nrp1+ VPCs demonstrated a dramatically greater response to hemodynamic stimuli by upregulating many arterial markers whereas Nrp1- VPCs have very little response. Surprisingly, these differences between Nrp1+ and Nrp1- VPCs are not evident with vascular endothelial growth factor (VEGF) treatment. Our data suggest that Nrp1+ VPCs may serve as the arterial progenitor by enhanced response to hemodynamic flow but not to VEGF, whereas Nrp1- VPCs lack the plasticity to become arterial ECs. The findings of this research indicate that Nrp1+ VPCs in the murine model act as an important step in the arterial differentiation process.
journal_name
Stem Cells Devjournal_title
Stem cells and developmentauthors
Kim D,Lee V,Dorsey TB,Niklason LE,Gui L,Dai Gdoi
10.1089/scd.2017.0240subject
Has Abstractpub_date
2018-04-01 00:00:00pages
441-455issue
7eissn
1547-3287issn
1557-8534journal_volume
27pub_type
杂志文章abstract::Rare heterozygous deletions in the neurexin 1 (NRXN1) gene robustly increase an individual's risk of developing neurological and psychiatric disorders. However, the molecular bases by which different mutations result in different clinical presentations, with variable penetrance, are unknown. To better understand the m...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2020.0017
更新日期:2020-09-01 00:00:00
abstract::Progenitor expansion during development is a highly regulated process dictating the final organ size, while expansion of specific progenitor populators can adjust the final cellular composition of the organ. Understanding factors involved in these pathways is required to develop cell-based therapies such as β-cell tra...
journal_title:Stem cells and development
pub_type: 杂志文章,评审
doi:10.1089/scd.2013.0106
更新日期:2013-11-15 00:00:00
abstract::Self-renewal and differentiation of endogenous stem cells (SCs) are essential for adult tissue homoeostasis and intrinsic healing capacity. In this study, we hypothesize that penis contains a small population of endogenous SCs, which might help rejuvenation of damaged erectile function. In this study, 60 newborn male ...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2014.0380
更新日期:2015-03-15 00:00:00
abstract::There are a limited number of therapies available to prevent heart failure following myocardial infarction. One novel therapy that is currently being pursued is the implantation of cardiac progenitor cells (CPCs); however, their responses to oxidative stress during differentiation have yet to be elucidated. The object...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2012.0673
更新日期:2013-09-01 00:00:00
abstract::Fertility clinics worldwide routinely produce a large volume of 'waste' follicular aspirate, which is potentially an abundant source of immature ovarian follicles. Current attempts to cultivate these further in vitro to yield viable mature oocytes for fertility treatment have not yet achieved much success. Instead, re...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2005.14.11
更新日期:2005-02-01 00:00:00
abstract::Aneurysm refers to the dilation of the vessel wall for more than 50%. Abdominal aortic aneurysm (AAA) refers to the dilation and weakening of all three layers of the abdominal aorta, which mostly occur infrarenally. The population aged above 50 years is at risk of AAA development, while a familiar history doubles the ...
journal_title:Stem cells and development
pub_type: 杂志文章,评审
doi:10.1089/scd.2014.0517
更新日期:2015-07-01 00:00:00
abstract::Human embryonic stem (hES) cells represent a potentially unlimited source of transplantable beta-cells for the treatment of diabetes. Here we describe a differentiation strategy that reproducibly directs HES3, an National Institutes of Health (NIH)-registered hES cell line, into cells of the pancreatic endocrine linea...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2007.0029
更新日期:2007-08-01 00:00:00
abstract::Tumor necrosis factor-α (TNF-α) has multiple effects on proliferation and differentiation of human mesenchymal stem cells. Transforming growth factor-activated kinase-1 (TAK1) mediates the activation of nuclear factor-kappa B (NF-κB), c-Jun N-terminal kinase (JNK), and p38 pathways in response to TNF-α. However, the r...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2014.0272
更新日期:2015-04-01 00:00:00
abstract::Traditionally, undifferentiated pluripotent human embryonic and induced pluripotent stem cells (hESCs and hiPSCs) have been expanded as monolayer colonies in adhesion culture, both in the presence or absence of feeder cells. However, the use of pluripotent stem cells poses the need to scale-up current culture methods....
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2010.0517
更新日期:2011-11-01 00:00:00
abstract::Occupational asthma (OA) is characterized by allergic airway inflammation and hyperresponsiveness, leading to progressive airway remodeling and a concomitant decline in lung function. The management of OA remains suboptimal in clinical practice. Thus, establishing effective therapies might overcome the natural history...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2013.0616
更新日期:2014-10-01 00:00:00
abstract::In this retrospective study, 209 patients with malignant disease were analyzed for levels of T-cell receptor excision circles (TRECs) for the first 24 months after allogeneic stem cell transplantation. CD3(+) cells were separated by direct antibody-coupled magnetic beads, followed by DNA extraction according to a stan...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2013.0588
更新日期:2014-07-15 00:00:00
abstract::Cell therapy with adult mesenchymal stem cells (MSCs) is a promising approach to regenerative medicine and autoimmune diseases. There are various approaches to improve the efficacy of MSC-based therapeutics, and MSC preparation as spheroidal aggregates, or MSC spheroids, is a novel preparatory and delivery method. Sph...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2015.0356
更新日期:2016-04-15 00:00:00
abstract::Extracellular stresses influence transcription factor (TF) expression and therefore lineage identity in the peri-implantation mouse embryo and its stem cells. This potentially affects pregnancy outcome. To understand the effects of stress signaling during this critical period of pregnancy, we exposed cultured murine e...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2014.0157
更新日期:2014-12-15 00:00:00
abstract::Mesenchymal stromal cells (MSCs) hold great promise in the field of regenerative medicine due to their ability to create a variable localized anti-inflammatory effect in injuries such as Crohn's disease and osteoarthritis or by incorporation in tissue engineered constructs. Currently, the MSC literature uses rodents f...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2019.0145
更新日期:2020-06-01 00:00:00
abstract::Pericytes play a crucial role in angiogenesis and vascular maintenance. They can be readily identified in vivo and isolated as CD146(+)CD34(-) cells from various tissues. Whether these and other markers reliably identify pericytes in vitro is unclear. CD146(+)CD34(-) selected cells exhibit multilineage potential. Thus...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2012.0415
更新日期:2013-09-01 00:00:00
abstract::Tendons and ligaments (T/L) are dense connective tissues of mesodermal origin. During embryonic development, the tendon-specific cells descend from a sub-set of mesenchymal progenitors condensed in the syndetome, a dorsolateral domain of the sclerotome. These cells are defined by the expression of the transcription fa...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2011.0150
更新日期:2012-04-10 00:00:00
abstract::Recent evidence shows that amniotic fluid (AF) contains multiple cell types derived from the developing fetus, and may represent a novel source of stem cells for cell therapy. In this study, we examined the paracrine factors released by human amniotic fluid-derived mesenchymal stem cells (AF-MSCs) and their ability to...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2009.0138
更新日期:2010-06-01 00:00:00
abstract::True tendon regeneration in human patients remains a vision of musculoskeletal therapies. In comparison to other mesenchymal lineages the biology of tenogenic differentiation is barely understood. Specifically, easy and efficient protocols are lacking that might enable tendon cell and tissue differentiation based on a...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2014.0124
更新日期:2014-08-15 00:00:00
abstract::Previous studies have transplanted a variety of neural stem cells (NSCs) to the eye in hopes of developing a therapy to replace retinal neurons lost to disease. Successful integration, survival, and differentiation of the cell types has been variably successful. At the moment, little is known about the fundamental bio...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2007.0051
更新日期:2008-02-01 00:00:00
abstract::Embryonic stem cells (ESCs) have the capacity to form all the tissues in the body and hence, directed differentiation of ESCs along specific lineages represents a means to generate therapeutically useful cell types. It has been postulated that, during in vitro differentiation, ES cells sequentially pass through simila...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2005.14.656
更新日期:2005-12-01 00:00:00
abstract::Mesenchymal stem cells (MSCs) can be mobilized from the bone marrow and enter the circulation. Conversely, MSCs can be recruited from the circulation and into the bone marrow. For these migratory pathways, MSCs have to traverse the bone marrow endothelium, in a basal-to-apical and apical-to-basal direction, respective...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2011.0025
更新日期:2012-02-10 00:00:00
abstract::In this study, we isolated and characterized spontaneously differentiated human embryonic stem cells (SD-hESCs) found in hESC colonies in comparison to the morphologically premature ESCs in the colonies to investigate the potential role of SD-hESCs in embryogenesis. SD-hESCs were distinguished from undifferentiated hE...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2013.0083
更新日期:2013-10-15 00:00:00
abstract::Collectively, lung diseases are one of the largest causes of premature death worldwide and represent a major focus in the field of regenerative medicine. Despite significant progress, only few stem cell platforms are currently available for cell-based therapy, disease modeling, and drug screening in the context of pul...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2014.0512
更新日期:2015-07-15 00:00:00
abstract::To understand which growth factors/cytokines can affect migration of mesenchymal stem cells (MSCs) to injured tissues, we compared the effects of many (26) growth factors/cytokines on the migration activity of rabbit and human MSCs using a microchemotaxis chamber. Among them, platelet-derived growth factor (PDGF)-BB, ...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2006.0032
更新日期:2007-02-01 00:00:00
abstract::Administration of human bone marrow-derived mesenchymal stem cells (BM-MSCs) significantly alleviates allergic airway inflammation. There are no studies that refer to the role of microRNAs (miRNAs) after the BM-MSCs treatment in airway allergic inflammation. We induced a mouse model of asthma and performed the transpl...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2015.0339
更新日期:2016-06-15 00:00:00
abstract::Primary periodontal ligament stem cells (PDLSCs) are known to possess multidifferentiation potential and exhibit an immunophenotype similar to that described for bone-marrow-derived mesenchymal stem cells. In the present study, bromo-deoxyuridine (BrdU)-labeled ovine PDLSCs implanted into immunodeficient mice survived...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2013.0490
更新日期:2014-05-01 00:00:00
abstract::Induced pluripotent stem cells (iPSCs) are somatic cells that have been reprogrammed to a pluripotent state via introduction of defined transcription factors. iPSCs are a valuable resource for regenerative medicine, but whether iPSCs are identical to embryonic stem cells (ESCs) remains unclear. In this study, we perfo...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2011.0243
更新日期:2012-05-20 00:00:00
abstract::Small molecules (SM) can greatly enhance the efficiency of induced pluripotent stem (iPS) cell generation, but the mechanisms by which they act have not been fully explored. We show here that an SM cocktail (NaB, PD03259, and SB431542) significantly promotes iPS cell generation from human fibroblasts, and NaB is more ...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2012.0650
更新日期:2013-08-15 00:00:00
abstract::Regenerative medicine is in demand of adult pluripotent stem cells (PSCs). The "Bonghan System (BHS)" was discovered and suggested to contain cells with regenerative capacity in the early 1960s. It had been ignored for a long time due to the lack of sufficient details of experiments, but about 37 years after the initi...
journal_title:Stem cells and development
pub_type: 杂志文章,评审
doi:10.1089/scd.2015.0024
更新日期:2015-10-01 00:00:00
abstract::Mesenchymal stem cells (MSCs) from bone marrow (BM) are widely used for bone and less for cartilage tissue regeneration due to their self-renewal and differentiating properties into osteogenic or chondrogenic lineages. This review considers the last decade of clinical trials involving a two-step procedure, by expandin...
journal_title:Stem cells and development
pub_type: 杂志文章,评审
doi:10.1089/scd.2012.0373
更新日期:2013-01-15 00:00:00