In this article the general strategy for bone regeneration using osteogenic stem cell and gene modified cells. In the past autogenous bone grafting was the most reliable and well documented technique for bone regeneration. However the patient usually is demanded the heavy burden for harvesting the grafted bone in the donor sites. In this circumstances the tissue engineering concept has been developed and introduced for clinical use. In this article the general strategy for bone regeneration using tissue engineering concept. We have tried two essential elements such as mesenchymal stem cell and sonic hedgehog gene to generate the bone tissue. Marrow expanded mesenchymal stem cell with ceramics scaffold have been studied and confirmed its usability for bone engineering especially for cavitary bone defects in the jaw bone. Also the sonic hedgehog gene modified fibroblasts could be useful for the systemic bone disease such as osteoporosis.
With advances in human genome projects we entered the era of functional genomics, medical genomics, and pharmacogenomics. However, it is a difficult task to carry out studies in all these areas in a short period of time. To accomplish this goal, we definitely need resources for research. These resources include cDNAs, peptides, antibodies, and genetically engineered mice. For medical genomics, we think it particularly important to have a large number of animal models for human diseases. Because we have to analyze pathogenesis and pathologic processes of disease development. To do these, we need a whole animal body. As one example, I descried a transgenic mouse model for human dominantly inherited disease, Familial amyloidotic polyneuropathy (FAP). Using this model, we demonstrated that; (1) amyloid deposition itself starts after 6 months of age, although the serum level of mutant protein reached at adult level at 4 weeks of age, (2) intrinsic and extrinsic environmental factors affect the development of amyloid deposition, and (3) the effect of newly developed drug can be evaluated using an animal model for FAP. Thus, transgenic mouse models for human diseases may play important roles in medical genomics.
Biodegradability of new types of polyglycolic acid (PGA)-collagen composite tubes for nerve regeneration was evaluated in the peritoneal cavity. Hollow PGA mesh tubes were coated with atelocollagen solution, dried at room temperature, and then subjected to dehydrothermal treatment (hollow composite tubes). Hollow composite tubes filled with collagen sponge were also investigated in this study (sponge tubes). Tubes were fixed at the parietal peritoneum of BALB/c mice, and excised 0.5, 1, 2 and 3 months after the insertion. The inner areas of the excised tubes were measured microscopically. The rate of remained inner areas were calculated and analyzed statistically by one-way ANOVA and Fisher's PLSD test. 1 month after the insertion, the inner areas of the sponge tubes were well maintained, though they were not maintained in the hollow composite tubes. The rate of remained inner areas of the sponge tubes was significantly larger than that of the hollow composite tubes until 2 months after insertion. These results suggest that sponge tubes are more suitable than hollow composite tubes for nerve regeneration in the peritoneal cavity.
Now in Japan, registered cord blood (CB) units are rapidly increasing in number and 1,205 CB units have been already shipped for cord blood transplantation (CBT) since 1997 by the end of August 2003 in Japan Cord Blood Bank Network system. Tokyo cord blood bank now registered up to 3,075 cryopreserved CB units in Japan Cord Blood Net Work (JCBNW), NETCORD and BMDW. All CBs have been processed by HES method and cryopreserved by controlled rate freezing by August 1999 and now cryopreserved by Bioarchive system, which contains the programmed freezing system. Our processing standard were based on the JCBNW and FACT/NETCORD standard. And quality management system has been based on the ISO 9002 since the first acquisition in 2001 April. 101 patients have received CBT from Tokyo Cord Blood Bank in Japan, also in USA, New Zealand, Chile and Vietnam through NETCORD or AsiaCORD by March 2002. Myeloid and platelet recovery in adults patients were not delayed compared to control child patients. But the recovery speed was influenced by number of CD34+ cell and colony formation. No significant difference between direct infusion to the patients after thawing and the removal of DMSO by dilution method at the CBT.
Adenoviral vectors primarily derived from the adenovirus serotype 5 (Ad5) are widely used for many gene transfer applications. However, they cannot efficiently infect hematopoietic cells because these cells barely express the coxsakie-adenoviral receptor (CAR). In this study, we developed a soluble fusion protein linking viral fibers and the c-Kit receptor to alter Ad5 tropism to immature hematopoietic cells. The CAR-SCF fusion protein consists of two extracellular domains of human CAR and mouse stem cell factor (SCF). CAR-SCF was added to culture of various human hematopoietic cell lines together with an Ad vector expressing the eGFP gene driven by the CMV promoter. CAR-SCF greatly enhanced Ad5-mediated gene transfer and eGFP expression in c-Kit+ cell lines. The ability of CAR-SCF to enhance Ad5 vector infectivity was dependent on cellular c-Kit expression levels. Furthermore, CAR-SCF also enhanced Ad5 vector transfection into human cord blood CD34+ cells. In conclusion, the fusion protein will allow us to efficiently retarget adenoviral vectors to c-Kit+ human immature hematopoietic cells by just adding the fusion protein to transduction culture with adenoviral vectors. This method has an advantage that all conventional Ad5 vectors can be used to infect hematopoietic cells without any reconstruction or modification of the vectors.
A 62 year-old woman with rheumatoid arthritis and scleroderma was given transfusion due to anemia. Eleven hours after transfusion, she revealed transfusion-related acute lung injury (TRALI). The origin of TRALI might be an presence of anti- granulocyte antibody in the plasma from her. Glucocortico-steroid therapy could rescue her from acute pulmonary edema. Since the serum concentration of surfactant protein D and KL-6 well reflected her repiratory conditions, these markers might be beneficial to clinical monitoring for TRALI. This paper is the first report suggesting the relationship between TRALI and clinical markers such as SP-D and KL-6, and the case with rheumatoid arthritis and scleroderma following TRALI.