Magnetic resonance (MR) tracking of magnetically labeled stem and progenitor cells is an emerging technology, leading to an urgent need for magnetic probes that can make cells highly magnetic during their normal expansion in culture. We have developed magnetodendrimers as a versatile class of magnetic tags that can efficiently label mammalian cells, including human neural stem cells (NSCs) and mesenchymal stem cells (MSCs), through a nonspecific membrane adsorption process with subsequent intracellular (non-nuclear) localization in endosomes. The superparamagnetic iron oxide nanocomposites have been optimized to exhibit superior magnetic properties and to induce sufficient MR cell contrast at incubated doses as low as 1 microg iron/ml culture medium. When containing between 9 and 14 pg iron/cell, labeled cells exhibit an ex vivo nuclear magnetic resonance (NMR) relaxation rate (1/T2) as high as 24-39 s-1/mM iron. Labeled cells are unaffected in their viability and proliferating capacity, and labeled human NSCs differentiate normally into neurons. Furthermore, we show here that NSC-derived (and LacZ-transfected), magnetically labeled oligodendroglial progenitors can be readily detected in vivo at least as long as six weeks after transplantation, with an excellent correlation between the obtained MR contrast and staining for beta-galactosidase expression. The availability of magnetodendrimers opens up the possibility of MR tracking of a wide variety of (stem) cell transplants.

Localization of activated natural killer (A-NK) cells in the microvasculature of growing tumors is the result of recognition of the intracellular and vascular cell-adhesion molecules ICAM-1 and VCAM-1 on the tumor endothelium, mediated by lymphocyte function-associated protein LFA-1 and vascular lymphocyte function-associated protein VLA-4. In vitro and in vivo studies of A-NK cell adhesion to endothelial cells showed that vascular endothelial growth factor (VEGF) promotes adhesion, whereas basic fibroblast growth factor (bFGF) inhibits adhesion through the regulation of these molecules on tumor vasculature. Thus, some angiogenic factors may facilitate lymphocyte recognition of angiogenic vessels, whereas others may provide such vessels with a mechanism that protects them from cytotoxic lymphocytes.

Diffusion-tensor imaging allowed for visualization of white matter tracts and was found to be beneficial in the surgical planning for patients with intrinsic brain tumors. The authors' experience with DT imaging indicates that anatomically intact fibers may be present in abnormal-appearing areas of the brain. Whether resection of these involved fibers results in subtle postoperative neurological deficits requires further systematic study.

Purpose: To categorize the varied appearances of tumoraltered white matter (WM) tracts on diffusion tensor eigenvector directional color maps. Materials and Methods:Diffusion tensor imaging (DTI) was obtained preoperatively in 13 patients with brain tumors ranging from benign to high-grade malignant, including primary and metastatic lesions, and maps of apparent diffusion coefficient (ADC), fractional anisotropy (FA), and major eigenvector direction were generated. Regions of interest (ROIs) were drawn within identifiable WM tracts affected by tumor, avoiding grossly cystic and necrotic regions, known fiber crossings, and gray matter. Patterns of WM tract alteration were categorized on the basis of qualitative analysis of directional color maps and correlation analysis of ADC and FA.Results: Four basic patterns of WM alteration were identified: 1) normal or nearly normal FA and ADC, with abnormal tract location or tensor directions attributable to bulk mass displacement, 2) moderately decreased FA and increased ADC with normal tract locations and tensor directions, 3) moderately decreased FA and increased ADC with abnormal tensor directions, and 4) near isotropy. FA and ADC were inversely correlated for Patterns 1-3 but did not discriminate edema from infiltrating tumor. However, in the absence of mass displacement, infiltrating tumor was found to produce tensor directional changes that were not observed with vasogenic edema, suggesting the possibility of discrimination on the basis of directional statistics. Conclusion:Tumor alteration of WM tracts tends to produce one of four patterns on FA and directional color maps. Clinical application of these patterns must await further study.

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Summary Fluid transport parameters in intracranial tumours influence the delivery of therapeutic agents and the resolution of peritumoral oedema. The tumour and cortex interstitial fluid pressure (IFP) and the cerebrospinal fluid pressure (CSFP) were measured during the growth of brain and pial surface tumours [R3230AC mammary adenocarcinoma (R3230AC) and F98 glioma (F98)] in rats. Intratumoral and intracranial pressures were also measured in rodents and patients treated with dexamethasone, mannitol and furosemide (DMF), and hypocapnia. The results show that (1) for the R3230AC on the pial surface, IFP increased with tumour volume and CSFP increased exponentially for tumours occupying a brain volume of 5% or greater; (2) in F98 with volumes of approximately 10 mm3, IFP decreased from the tumour to the cortex, whereas for tumour volumes > 16 mm3 IFP equilibrates between F98 and the cortex; (3) DMF treatment reduced the IFP of intraparenchymal tumours significantly and induced a pressure gradient from the tumour to the cortex; and (4) in 11 patients with intracranial tumours, the mean IFP was 2.0 ± 2.5 mmHg. In conclusion, the IFP gradient between intraparenchymal tumours and the cortex decreases with tumour growth, and treatment with DMF can increase the pressure difference between the tumour and surrounding brain. The results also suggest that antioedema therapy in patients with brain tumours is responsible in part for the low tumour IFP.Keywords: interstitial fluid pressure; microvascular pressure; brain tumours in rodents; intracranial tumours in patients; antioedema therapy Studies from our group and other investigators have shown that the interstitial fluid pressure (IFP) of human tumours in situ is significantly elevated compared with normal tissues Roh et al, 1991;Gutmann et al, 1992;Less et al, 1992;Curti et al, 1993;Arbit et al, 1994;Nathanson and Nelson, 1994). In most normal tissues the IFP is around 0 mmHg while for the different carcinoma types measured to date the mean IFPs vary between 14 and 30 mmHg. In general, in human and experimental tumours the IFP increases with tumour size (Jain, 1987a;Boucher et al, 1990Boucher et al, , 1991Boucher et al, , 1995Gutmann et al, 1992;Lee et al, 1992;Nathanson and Nelson, 1994). However, in other studies, the IFP was found to be independent of the tumour volume (Less et al, 1992;Curti et al, 1993;Boucher et al, 1995;Tufto and Rofstad, 1995;Znati et al, 1996). Measurements in experimental tumours have demonstrated that (1) the IFP is uniform throughout the centre of tumours and drops steeply in the tumour periphery or in the normal tissue surrounding the tumour (Boucher et al, 1990;Boucher and Jain, 1992;DiResta et al, 1993) and (2) that the hydrostatic and oncotic pressures in the vascular and interstitial space are at or close to equilibrium Jain, 1989, Boucher andStohrer et al, 1995). The similarity in hydrostatic pressures between the microvascular and interstitial space is thought to be a major mechanism limiting the convective delivery of large therapeut...

Cellular transplantation strategies have been explored for the treatment of spinal cord injury. In particular, olfactory nerve ensheathing cell (OEC) transplantation has been reported to improve functional outcome following injury. We investigated the effect of OEC transplantation using cells derived from adult animals on the restoration of function following a contusion injury to the spinal cord. The NYU impactor was used to create a moderate to severe spinal cord injury in 17 rats. Hoescht stained cultured OECs derived from adult rats (n = 7) or culture medium alone (n = 10) were injected into the injury site immediately following injury. Histological and functional outcomes were measured using immunohistochemistry and the Basso, Beattie, and Bresnahan (BBB) scale. All animals transplanted with OECs were found to have surviving Hoescht positive cells within the spinal cord when sacrificed 6 weeks following injury. Immunohistochemical staining of the explanted cords revealed that the surviving cells stained positively for nerve growth factor receptor. Functional outcomes were not different between the transplanted and control groups. OECs transplanted immediately following a contusion injury to the spinal cord survive during the first 6 weeks following injury. These cells do not appear to influence functional outcome during the first 6 weeks following injury. Additional studies are required in order to definitively determine the utility of this type of cellular transplantation for spinal cord injury.

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