To examine whether transplantation of human mesenchymal stem cells (MSCs) could reconstruct the corneal damage and also whether grafted MSCs could differentiate into corneal epithelial cells, we isolated MSCs from healthy donors. After growth and expansion on amniotic membrane, cells were transplanted into rat corneas 7 days after chemical burns. Reconstruction of the damaged cornea and the rat vision were measured once a week by slit lamp and by an optokinetic head-tracking instrument, respectively. Corneas were then cut out, fixed, and imbedded for immunofluorescent study of the expression of keratin 3 and keratin-pan as epithelial cell markers. Expression of CD45, interleukin 2, and metalloproteinase-2 was also investigated for inflammation and inflammation-related angiogenesis. The data showed that transplantation of MSCs, like limbal epithelial stem cells, successfully reconstructed damaged rat corneal surface. Interestingly, the therapeutic effect of the transplantation may be associated with the inhibition of inflammation and angiogenesis after transplantation of MSCs rather than the epithelial differentiation from MSCs. This study provides the first line of evidence that MSCs can be used for reconstruction of damaged corneas, presenting a new source for autotransplantation in the treatment of corneal disorders. STEM CELLS 2006;24:315-321

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The International Society for Stem Cell Research (ISSCR) task force that developed new Guidelines for the Clinical Translation of Stem Cells discusses core principles that should guide the responsible transition of basic stem cell research into appropriate clinical applications.

OCT4 is a pivotal transcription factor in maintaining the pluripotency and self-renewal capacities of embryonic stem (ES) cells. Human OCT4 can generate two isoforms by alternative splicing, termed OCT4A and OCT4B. OCT4A confers the stemness properties of ES cells, whereas the function of OCT4B is unknown. We present here the diverse protein products and a novel function of OCT4 gene. A single OCT4B mRNA can encode three isoforms by alternative translation initiation at AUG and CUG start codons, respectively. A putative internal ribosome entry site (IRES) has been identified in OCT4B mRNA accounting for the translation mechanism. The OCT4B-190 is upregulated under stress conditions and it may protect cell against apoptosis under stress. This work evokes the significance to distinguish the biological function of the protein products of OCT4. The OCT4 gene, by the regulation of alternative splicing and alternative translation initiation, may carry out more crucial roles in many biological events.

The re-creation of the tumor microenvironment including tumor-stromal interactions, cell-cell adhesion and cellular signaling is essential in cancer-related studies. Traditional two-dimensional (2D) cell culture and animal models have been proven to be valid in some areas of explaining cancerous cell behavior and interpreting hypotheses of possible mechanisms. However, a well-defined three-dimensional (3D) in vitro cancer model, which mimics tumor structures found in vivo and allows cell-cell and cell-matrix interactions, has gained strong interest for a wide variety of diagnostic and therapeutic applications. This communication attempts to provide a representative overview of applying 3D in vitro biological model systems for cancer related studies. The review compares and comments on the differences in using 2D models, animal models and 3D in vitro models for cancer research. Recent technologies to construct and develop 3D in vitro cancer models are summarized in aspects of modeling design, fabrication technique and potential application to biology, pathogenesis study and drug testing. With the help of advanced engineering techniques, the development of a novel complex 3D in vitro cancer model system will provide a better opportunity to understand crucial cancer mechanisms and to develop new clinical therapies.