Differentiation of embryonic stem cells towards hematopoietic cells: Progress and pitfalls

Department of Medicine, Stem Cell Institute, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Current opinion in hematology (Impact Factor: 3.97). 08/2008; 15(4):312-8. DOI: 10.1097/MOH.0b013e328302f429
Source: PubMed


Hematopoietic development from embryonic stem cells has been one of the most productive areas of stem cell biology. Recent studies have progressed from work with mouse to human embryonic stem cells. Strategies to produce defined blood cell populations can be used to better understand normal and abnormal hematopoiesis, as well as potentially improve the generation of hematopoietic cells with therapeutic potential.
Molecular profiling, phenotypic and functional analyses have all been utilized to demonstrate that hematopoietic cells derived from embryonic stem cells most closely represent a stage of hematopoiesis that occurs at embryonic/fetal developmental stages. Generation of hematopoietic stem/progenitor cells comparable to hematopoietic stem cells found in the adult sources, such as bone marrow and cord blood, still remains challenging. However, genetic manipulation of intrinsic factors during hematopoietic differentiation has proven a suitable approach to induce adult definitive hematopoiesis from embryonic stem cells.
Concrete evidence has shown that embryonic stem cells provide a powerful approach to study the early stage of hematopoiesis. Multiple hematopoietic lineages can be generated from embryonic stem cells, although most of the evidence suggests that hematopoietic development from embryonic stem cells mimics an embryonic/fetal stage of hematopoiesis.

3 Reads
  • Source
    • "Vascular endothelial growth factor and its receptor play an important role in hematopoiesis. Hemangioblast differentiation from human embryonic stem cells is dependent upon expression of VEGFR2 (Flk1/KDR) [9] [10]. Furthermore , hematopoietic stem cells (HSC) express VEGFR-1 and -2 [11] [12] [13], and are essential for the migration of these cells [14]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Sorafenib is a vascular endothelial growth factor receptor tyrosine-kinase inhibitor currently used in several malignancies. While not a traditional cytotoxic chemotherapeutic agent, hematological toxicities have been reported with this drug but the incidence and risk have not been formerly assessed. We performed a meta-analysis to determine the incidence and risk of hematologic toxicities associated with sorafenib use. The databases of Medline were searched for articles from 1966 to May 2010. Abstracts presented at the American Society of Clinical Oncology meetings were also searched. Eligible studies include randomized trials with sorafenib, and adequate safety data profile reporting anemia, neutropenia, lymphopenia or thrombocytopenia. Statistical analyses were conducted to calculate the summary incidence, RR and 95% confidence intervals (CI). A total of 3221 patients were included. The incidences of sorafenib-associated all-grade anemia, neutropenia, thrombocytopenia and lymphopenia were 43.9%, 18.0%, 25.3% and 34.1%, respectively. The incidences of high-grade events were 2.0%, 5.1%, 4.0% and 13.1%, respectively. Sorafenib was associated with a decreased risk of high-grade anemia (RR=0.62; 95% CI, 0.39-0.98), an increased risk of all-grade (RR=1.69; 95% CI, 1.33-2.17) and high-grade (RR=1.61; 95% CI, 1.02-2.57) neutropenia, all-grade (RR=2.56; 95% CI, 1.37-4.80) and high-grade (RR=3.63; 95% CI, 1.98-6.66) thrombocytopenia, and high-grade lymphopenia (RR=1.84; 95% CI, 1.22-2.78). Stratified analysis by the presence or not of concomitant chemotherapy demonstrated similar risks. Independent of cytotoxic chemotherapy, sorafenib has significant hematologic toxicities, with a decreased risk of anemia and increased risk of neutropenia, thrombocytopenia and lymphopenia.
    Critical reviews in oncology/hematology 12/2010; 80(2):291-300. DOI:10.1016/j.critrevonc.2010.11.007 · 4.03 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A system compensation method applied to an inverse synthetic aperture radar (ISAR) with STRETCH processing is presented in this paper. Some of the key issues causing sidelobes in ISAR design are discussed and the simulation and experiment results are given. This method can compensate not only the system distortion but the quadrature nonbalance. The simulation and experiment results demonstrate that this system compensation method is of feasibility and efficiency
    Aerospace and Electronics Conference, 1994. NAECON 1994., Proceedings of the IEEE 1994 National; 06/1994
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The envelope constrained (EC) filtering problem is concerned with the design of a filter with minimum gain to white input noise and with a response to a given signal that fits into a prescribed envelope. Using the discrete-time orthonormal Laguerre network, the EC filtering problem is posed as a quadratic programming (QP) problem with affine inequality constraints. An iterative algorithm for solving this QP problem is proposed which serves as a basis for the derivation of adaptive algorithms for applications where the parameters of the underlying signal model are either not known or varying with time.
    Proceedings - ICASSP, IEEE International Conference on Acoustics, Speech and Signal Processing 01/1996; 3:1363-1366. DOI:10.1109/ICASSP.1996.543680
Show more