Differentiation of embryonic stem cells towards hematopoietic cells: progress and pitfalls.
ABSTRACT 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.
SourceAvailable from: Sheng Ding[Show abstract] [Hide abstract]
ABSTRACT: Stem cells, including both pluripotent stem cells and multipotent somatic stem cells, hold great potential for interrogating the mechanisms of tissue development, homeostasis and pathology, and for treating numerous devastating diseases. Establishment of in vitro platforms to faithfully maintain and precisely manipulate stem cell fates is essential to understand the basic mechanisms of stem cell biology, and to translate stem cells into regenerative medicine. Chemical approaches have recently provided a number of small molecules that can be used to control cell self-renewal, lineage differentiation, reprogramming and regeneration. These chemical modulators have been proven to be versatile tools for probing stem cell biology and manipulating cell fates toward desired outcomes. Ultimately, this strategy is promising to be a new frontier for drug development aimed at endogenous stem cell modulation.Cell Research advance online publication 25 December 2012; doi:10.1038/cr.2012.182.Cell Research 12/2012; DOI:10.1038/cr.2012.182 · 11.98 Impact Factor
[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 abstract] [Hide abstract]
ABSTRACT: Background: Human embryonic stem cells (hESCs) have been derived and maintained on mouse embryonic fibroblast feeders to keep their undifferentiated status. To realize their clinical potential, a feeder-free and scalable system for large scale production of hESCs and their differentiated derivatives is required. Materials & methods: hESCs were cultured and passaged on serum/feeder-free 3D microcarriers for five passages. For embryoid body (EB) formation and hemangioblast differentiation, the medium for 3D microcarriers was directly switched to EB medium. Results: hESCs on 3D microcarriers maintained pluripotency and formed EBs, which were ten-times more efficient than hESCs cultured under 2D feeder-free conditions (0.11 ± 0.03 EB cells/hESC input 2D vs 1.19 ± 0.32 EB cells/hESC input 3D). After replating, EB cells from 3D culture readily developed into hemangioblasts with the potential to differentiate into hematopoietic and endothelial cells. Furthermore, this 3D system can also be adapted to human induced pluripotent stem cells, which generate functional hemangioblasts with high efficiency. Conclusion: This 3D serum- and stromal-free microcarrier system is important for future clinical applications, with the potential of developing to a GMP-compatible scalable system.Regenerative Medicine 07/2013; 8(4):413-24. DOI:10.2217/rme.13.36 · 3.87 Impact Factor