Stem cells directed differentiation

In a recent study, scientists directed mouse embryonic stem cells to differentiate into DA neurons by introducing the gene Nurr 1. When transplanted into the brains of a rat model of Parkinson s disease, these stem cell-derived DA neurons reinnervated the brains of the mouse Parkinson s disease model, released dopamine, and improved motor function. 

Anderson, J.M., Kushwaha, M., Tambralli, A., Beilis, S.L., Camata, R.P., Jun, H.W. Osteogenic differentiation of human mesenchymal stem cells directed by extracellular matrix-mimicking ligands in a biomimetic self-assembled peptide amphiphile nanomatrix. Biomacromolecules 10, 2935-2944 (2009)... 

Nakajima M, Ishimuro T, Kato K, Ko IK, Hirata I, Arima Y, Iwata H (2007) Combinatorial protein display for the cell-based screening of biomaterials that direct neural stem cell differentiation. Biomaterials 28 1048-1060... 

Figure 14.18 Some cell types reported to have been produced via in vitro directed differentiation from either mouse or human embryonic stem cells. Potential uses for such cell types in regenerative medicines are listed in italics...

The main focus of stem cell research over the last few decades has been directed to embryonic stem cells. However, more recently, research upon and an understanding of various populations of adult stem cells has gathered pace. Adult stem cells are undifferentiated cells found amongst differentiated cells in a tissue or organ. These cells can renew themselves and can differentiate to yield the major cell types characteristic of the tissue in which they reside. The main physiological role of adult stem cells, therefore, appears to be to maintain and to repair (to a certain extent at least) the tissue in which they reside. 

Figure 14.19 Simplified schematic overview of the directed differentiation of human embryonic stem cells to form differentiated dopamine like neurons. The full pathway details are available in Yan, Y., Yang, D., Zarnowska, E.D., Du, Z., Werbel, B., Valliere, C., etai 2005. Directed differentiation of dopaminergic neuronal subtypes from human embryonic stem cells. Stem Cells 23, 781-790. FGF fibroblast growth factor SHH sonic hedgehog (a regulatory protein)...

FIGURE 29-2 Stem cells undergo symmetric divisions to increase the pool size of stem cells, or asymmetric divisions to give rise to a committed progenitor cell and another stem cell. Committed progenitor cells may go on to differentiate immediately to directly replace mature cells lost in response to injury or disease. Alternatively, expansion factors may stimulate extensive division of a specific progenitor cell, and produce large numbers of a mature cell type. 

Wichterle, H., Lieberam, I., Porter, J. A. and Jessell, T. M. Directed differentiation of embryonic stem cells into motor neurons. Cell 110 385-397, 2002. 

Chai C, Leong KW (2007) Biomaterials approach to expand and direct differentiation of stem cells. Mol Ther 15 467 180. 

The stem cell line Myl-D7 not only expresses differentiation markers of all lineages but is dependent for growth on self-renewing stem cells within the Myl-D7 clone which spontaneously differentiates along the lymphoid, myeloid, or erythroid direction (Itoh et ah, 1996). Supernatant of MS5 induces short term growth of Myl-D7 cells. This may indicate that at least soluble stem cell growth factors are secreted by MSS cells. 

Cord blood has long been used as a source of MSCs for bone marrow transplantation. The stem cell compartment is more abundant and less mature in cord blood than in bone marrow. Moreover, MSCs in cord blood have a higher proliferative potential because of their extended lifespan and longer telomeres [91-94]. Not only can cord-blood MSCs be harvested without morbidity to the donor, but they also display a robust in vitro capacity for directable or spontaneous differentiation into mesodermal, endodermal, and ectodermal cell fates. Cord-blood MSCs are CD45 and HLA-II and can be expanded without losing their pluripotency. Therefore, cord blood is also undergoing preclinical evaluation as a possible easily accessible source of multipotent cells. 

G-CSF is a glycoprotein produced by macrophages, endothelium and various leukocytes. It stimulates the bone marrow to produce granulocytes and stem cells and then directs their migration from the bone marrow to the peripheral blood. G-CSF is a growth factor for the proliferation, differentiation, effector function and survival of neutrophils. The gene for G-CSF is located on chromosome 17, locus qll.2-ql2. 

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