Although studies in vivo revealed promising results in bone regeneration after implantation of scaffolds together with osteogenic progenitor cells, basic questions remain how material surfaces control the biology of mesenchymal stem cells (MSC). We used human MSC derived from bone marrow and studied the osteogenic differentiation on calcium phosphate surfaces. In osteogenic differentiation medium MSC differentiated to osteoblasts on hydroxyapatite and BONITmatrix®, a degradable xerogel composite, within 14 days. Cells revealed a higher alkaline phosphatase (ALP) activity and increased RNA expression of collagen I and osteocalcin using real-time RTPCR compared with cells on tissue culture plastic. To test whether material surface characteristics alone are able to stimulate osteogenic differentiation, MSC were cultured on the materials in expansion medium without soluble additives for osteogenic differentiation. Indeed, cells on calcium phosphate without osteogenic differentiation additives developed to osteoblasts as shown by increased ALP activity and expression of osteogenic genes, which was not the case on tissue culture plastic. Because we reasoned that the stimulating effect on osteogenesis by calcium phosphate surfaces depends on an altered cell–extracellular matrix interaction we studied the dynamic behaviour of focal adhesions using cells transfected with GFP labelled vinculin. On BONITmatrix®, an increased mobility of focal adhesions was observed compared with cells on tissue culture plastic. In conclusion, calcium phosphate surfaces are able to drive MSC to osteoblasts in the absence of osteogenic differentiation supplements in the medium. An altered dynamic behaviour of focal adhesions on calcium phosphate surfaces might be involved in the molecular mechanisms which promote osteogenic differentiation.

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The prognosis of pancreatic adenocarcinoma is poor and agent ifosfamide to toxic metabolites. Administration of current treatment ineffective. A novel treatment strategy is ifosfamide to tumour-bearing mice that were recipients of described here using a mouse model system for pancreatic implanted encapsulated cells results in partial or even comcancer. Cells that have been genetically modified to plete tumour ablation. These results suggest that in situ express the cytochrome P450 2B1 enzyme are encapsuchemotherapy with genetically modified cells in an lated in cellulose sulphate and implanted into pre-estabimmunoprotected environment may prove useful for lished tumours derived from human pancreatic cells. application in man. Cytochrome P450 2B1 converts the chemotherapeutic

Background and Purpose-Strokes have especially devastating implications if they occur early in life; however, only limited information exists on the characteristics of acute cerebrovascular disease in young adults. Although risk factors and manifestation of atherosclerosis are commonly associated with stroke in the elderly, recent data suggests different causes for stroke in the young. We initiated the prospective, multinational European study Stroke in Young Fabry Patients (sifap) to characterize a cohort of young stroke patients. Methods-Overall, 5023 patients aged 18 to 55 years with the diagnosis of ischemic stroke (3396) *Drs Rolfs, Fazekas and Grittner contributed equally to this work. Authors contributions: Dr Rolfs has conceptualized, initiated, and designed and organized the study, has been involved in the recruitment of the patients, and wrote significant parts of the manuscript. Dr Fazekas was involved in the study planning and has done together with Drs Enzinger and Schmidt the analysis of all MRI scans; this group was mainly involved in the statistical analysis of the MRI data. Drs Martus, Grittner, Holzhausen have taken responsibility for all statistical analysis and for the data structure of the total data bank. Drs Dichgans, Böttcher, Tatlisumak, Tanislav, Jungehulsing, Putaala, Huber, Bodechtel, Lichy, Hennerici, Kaps, Meyer, Kessler have been most active in the recruitment of the patients, drafting the manuscript and significantly influencing the scientific discussion. Dr Heuschmann was involved in drafting the manuscript and influencing the scientific discussion. Dr Norrving chaired the steering and publication committees of sifap, has written parts of the manuscript, and has significantly influenced the scientific discussions. Drs Lackner and Paschke, H. Mascher, Dr Riess have been involved in the laboratory analyses. Dr Kolodny has mostly contributed to the discussion of the Fabry cases. Dr Giese assisted in writing and editing the manuscript. All authors have reviewed, critically revised and approved the final version of the manuscript.The sponsors of the study had no role in the study design, data collection, data analysis, interpretation, writing of the manuscript, or the decision to submit the manuscript for publication. The academic authors had unrestricted access to the derived dataset, and assume full responsibility for the completeness, integrity, and interpretation of the data, as well as writing the study report and the decision to submit for publication.†Listed in Appendix I in the online-only Data Supplement. Jeffrey L. Saver, MD, was guest editor for this article.