Cancer Cell Int. 2008; 8: 9
One emerging strategy is to use the tumor tracking capacity inherent in many stem cell populations to deliver therapeutic agents to the brain cancer cells. Current limitations of the stem cell therapy strategy include that stem cells are treated as a single entity and lack of uniform technology is adopted for selection of clinically relevant sub-populations of stem cells.,
Blood. 2006 March 1; 107(5): 2170–2179.
Hematopoietic stem cell (HSC) self-renewal is driven by both intrinsic and extrinsic factors, but the molecular mechanism specifying whether developmental potential is lost or retained during asymmetric cell divisions is unknown. Serial transplantation studies have clearly indicated that self-renewal potential of HSCs is impaired after replicative stress.1,2 HSC activity may be irreversibly lost in a single cell division,3,4 indicating that the epigenetic regulation of gene expression, largely dictated by the histone code, may play an important role. Recently, substantial attention has focused on the role of Polycomb group (PcG) proteins in stem cell self-renewal.,
The Journal of Neuroscience, December 5, 2007, 27(49):13499-13512
Figure 1. Local circuitry and experimental arrangement. A, Schematic drawing of a Purkinje cell and a single climbing fiber, oriented in the parasagittal plane. The smooth, proximal dendrites of the ganglionic layer give rise to the long, spine-covered dendrites of the molecular layer. The molecular layer dendrites are primarily unbranched and traverse the molecular layer in parallel to each other. The climbing fiber (shown in red) terminates only on the soma and smooth dendrites of the ganglionic layer. SM1 and SM2, Stimulation of molecular layer to activate parallel fibers; SG, stimulation of deep layer to activate climbing fibers; Rec, recording. B, Diagram of the local circuitry of the central lobes of the mormyrid cerebellum. Some essential features of the local circuitry are shown. The climbing fiber terminates in the ganglionic layer and does not enter the molecular layer. The Purkinje cell terminates locally on the efferent cell. Parallel fibers excite the molecular layer dendrites of efferent cells, as well as the dendrites of Purkinje cells, Golgi cells, and stellate cells. Inhibitory neurons are shown in gray. cf, Climbing fiber; Efc, efferent cell; GaL, ganglionic layer; Goc, Golgi cell; Grc, granule cell; GrL, granule layer; IO, inferior olive; mf, mossy fiber; ML, molecular layer; Pc, Purkinje cell; pf, parallel fiber; Stc, stellate cell. C, Responses of a Purkinje cell to parallel fiber activation by SM in current-clamp configuration. An all-or-none broad spike arises from the parallel fiber-evoked EPSP on one sweep. D, Responses of a Purkinje cell to climbing fiber activation by SG in current-clamp configuration. The all-or-none CF-evoked EPSP can evoke a broad spike. E, Responses of a Purkinje cell to climbing fiber activation by SG in voltage-clamp configuration. The CF evokes a large all-or-none EPSC. Note that small EPSCs or EPSPs are visible in D and E when climbing fiber activation failed, perhaps caused by activation of a small number of ascending granule cell axons by SG.
J. Clin. Invest. 118(1): 133-148 (2007).
SN enhances stem cell mobilization and homing to brain. BrdU labeling and analysis by transgenic GFP-chimeric mice were used to demonstrate the homing and engraftment of intrinsic neural progenitor cells (INPCs) and BMSCs to the brain. Seven days after cerebral ischemia, in SN-treated rats (n = 6), cumulative BrdU labeling revealed a few BrdU-immunoreactive cells in the ipsilateral cortex near the infarct boundary (Figure 6, A–D) and subventricular region of ischemic hemisphere (Figure 6, E–H). BrdU-immunoreactive cells were also found around the lumen of varying calibers of blood vessels in the perivascular portion of the ischemic hemisphere (Figure 6, I–L). BrdU pulse labeling showed significantly more BrdU-immunoreactive cells in the penumbral region in SN-treated rats than saline control rats (n = 8 per group; Figure 6M). Moreover, in transgenic GFP-chimeric mice, a significant increase of GFP+ cells (showing green fluorescence) was observed in the penumbral region of SN-treated mice compared with controls (Figure 6N)
J. Clin. Invest. 118(1): 161-172 (2007)
Primary cell cultures. Schwann cells were isolated from sciatic nerves of 1-day-old Sprague Dawley rats as previously described (43, 73) and further selected from fibroblasts using anti-fibronectin antibody and rabbit complement. This method yielded Schwann cell cultures that were about 99% pure, as assessed by immunofluorescence microscopy for S100, a specific marker of Schwann cells. Primary Schwann cells were maintained in DMEM containing 10% FBS, 100 U/ml penicillin, 100 μg/ml streptomycin, 21 μg/ml bovine pituitary extract, and 4 μM forskolin (complete medium) at 37°C under humidified 5.0% CO2. Schwann cell cultures were passaged no more than 4 times before conducting experiments.
j immunol. 2007 july 15 179(2): 939–949.
T cells respond to infection by becoming activated proliferating effector cells. After the expansion of a large population of effector cells, the majority of the cells die by apoptosis. Apoptosis promotes homeostasis in the T cell compartment and eliminates potentially pathogenic effector T cells. A variety of molecules have been implicated in this process, yet the overall regulation of apoptosis in effector T cells is not understood. The regulation of apoptosis in T cells has been recently reviewed
