ABSTRACT
BACKGROUND: Engineered cell sheet transplantation has been considered an alternative physiological therapy for endocrine disorders. In this study, we attempted to fabricate functional human thyroid cell sheets using the engineering technology by culturing primary thyrocytes in free-feeder monolayers and assessed their proliferation and function in two different media. METHODS: The non-tumorous tissues (approximately 2 g) were dissected during surgery. Primary human thyroid cells were isolated by mechanical dispersion and treatment with isolation solution. The cells were cultured on tissue culture dishes or temperature-responsive culture dishes to induce the formation of detached cell sheets. RESULTS: Primary thyroid cells isolated from nine patients were positive for thyroid transcription factor 1, thyroglobulin (TG) and cytokeratin 7. Cell sheets with follicles were fabricated by cells incubated in both Dulbecco's Modified Eagle Medium (DMEM) and hepatocyte-defined medium (HDM) culture medium. The diameter and thickness of sheets fabricated in HDM were larger and thicker than those fabricated from DMEM. Furthermore, the cells incubated in HDM secreted higher levels of fT3 and fT4 than those incubated in DMEM. The thyroid peroxidase and TG mRNA of cells maintained in HDM were higher than those in cells maintained in DMEM. CONCLUSION: HDM appears suitable as a culture medium for maintaining primary thyrocytes and fabricating functional cell sheets. These in vitro findings may contribute to the development of appropriate culture conditions for human thyrocytes as well as engineered functional cell sheets.
Subject(s)
Humans , Eagles , In Vitro Techniques , Iodide Peroxidase , Keratin-7 , RNA, Messenger , Thyroglobulin , Thyroid Gland , Transcription FactorsABSTRACT
Background:Pancreas ductal adenocarcinoma (PDAC) remains the mostmalignant digestive disease, but several treatment strategies for PDAC have beendeveloped. Here we describe some current topics regarding the treatment ofPDACs in Nagasaki, Japan.1: Prevention of pancreas fistula (PF) after pancreas resectionAdjuvant chemotherapy for PDAC was demonstrated to be useful to prolongpatients’ survival after the resection of PDAC. To introduce adjuvant chemotherapyfor PDAC quickly, it is important to prevent the development of a PF afterpancreas resection. We evaluated the safety and efficacy of early drain removalon postoperative day 1 after distal pancreatectomy (DP; n=71), and we found thatearly drain removal was safe and effective for preventing grade B/C PFs (0% vs.late removal 16%; p<0.001).2: Laparoscopic surgery for PDACLaparoscopic distal pancreatectomy (Lap-DP) for low-grade malignant tumors atthe left side of the pancreas has been recognized to be safe and feasible, and afew studies have already obtained similar findings for PDAC compared to openDP. We have been performing the Lap-DP for PDACs without invasion beyondthe pancreas, and the modified radical antegrade modular pancreatosplenectomy(mRAMPS) is conducted at our institute. The plexus around the celiac artery orsuperior mesenteric artery is dissected to a limited extent. Histologically, all of ourPDAC patients who underwent a Lap-DP (n=5) achieved an R0 resection.3: Dendritic cell-based therapeutic vaccination for PDACThe treatment of unresectable or recurrent PDAC is not promising. We startedadministering a dendritic cell-based therapeutic vaccination in such cases alongwith the use of the anticancer drugs gemcitabine and/or S-1. A total of eightpatients received this therapy, and it seemed that the patients with recurrenceafter resection and those who had strong delayed-type hypersensitivity aroundthe injected lesion had a favorable prognosis, although the results were obtainedwith a small number of patients.Conclusions:Our recent treatments for PDAC are feasible and useful. It is important to developvarious ways to prolong the survival of PDAC patients.
ABSTRACT
Background:Pancreas ductal adenocarcinoma (PDAC) remains the most malignant digestive disease, but several treatment strategies for PDAC have been developed. Here we describe some current topics regarding the treatment of PDACs in Nagasaki, Japan. 1: Prevention of pancreas fistula (PF) after pancreas resection Adjuvant chemotherapy for PDAC was demonstrated to be useful to prolong patients’ survival after the resection of PDAC. To introduce adjuvant chemotherapy for PDAC quickly, it is important to prevent the development of a PF after pancreas resection. We evaluated the safety and efficacy of early drain removal on postoperative day 1 after distal pancreatectomy (DP; n=71), and we found that early drain removal was safe and effective for preventing grade B/C PFs (0% vs. late removal 16%; p<0.001). 2: Laparoscopic surgery for PDAC Laparoscopic distal pancreatectomy (Lap-DP) for low-grade malignant tumors at the left side of the pancreas has been recognized to be safe and feasible, and a few studies have already obtained similar findings for PDAC compared to open DP. We have been performing the Lap-DP for PDACs without invasion beyond the pancreas, and the modified radical antegrade modular pancreatosplenectomy (mRAMPS) is conducted at our institute. The plexus around the celiac artery or superior mesenteric artery is dissected to a limited extent. Histologically, all of our PDAC patients who underwent a Lap-DP (n=5) achieved an R0 resection. 3: Dendritic cell-based therapeutic vaccination for PDAC The treatment of unresectable or recurrent PDAC is not promising. We started administering a dendritic cell-based therapeutic vaccination in such cases along with the use of the anticancer drugs gemcitabine and/or S-1. A total of eight patients received this therapy, and it seemed that the patients with recurrence after resection and those who had strong delayed-type hypersensitivity around the injected lesion had a favorable prognosis, although the results were obtained with a small number of patients. Conclusions: Our recent treatments for PDAC are feasible and useful. It is important to develop various ways to prolong the survival of PDAC patients.