RESUMEN
Peripheral nerve injury (PNI) is a relatively frequent type of trauma that results in the suffering of many patients worldwide every year. Schwann cells (SCs) are expected to be applied in cell therapy because of their ability to promote peripheral nerve regeneration. However, the lack of clinically renewable sources of SCs hinders the application of SC-based therapies. Adipose-derived stem cells (ADSCs) have generated great interest in recent years because of their multipotency and ease of harvest, and they have already been verified to differentiate into Schwann-like cells (SLCs) in vitro. However, the efficiency of differentiation and the functions of SLCs remain unsatisfactory. We newly generated three-dimensional (3D) SLC spheroids from ADSCs using a modified protocol with human recombinant peptide (RCP) petaloid µ-piece. Morphological analysis, gene expression analysis by qRT-PCR, ELISA measurement of the secretion capabilities of neurotrophic factors, and neurite formation assay were performed to evaluate the functions of these 3D SLCs in vitro. Motor function recovery was measured in a sciatic nerve injury mouse model to analyze the nerve regeneration-promoting effect of 3D SLCs in vivo. The differentiation efficiency and the secretion of neurotrophic factors were enhanced in 3D SLCs compared with conventional SLCs. 3D SLCs could more effectively promote neurite growth and longer neurite extension in a neuron-like SH-SY5Y model. Additionally, 3D SLCs had a better therapeutic effect on nerve regeneration after transplantation into the sciatic nerve injury mouse model. These findings demonstrated that the potential of ADSC-derived SLCs to promote nerve regeneration could be significantly increased using our modified differentiation protocol and by assembling cells into a 3D sphere conformation. Therefore, these cells have great potential and can be used in the clinical treatment of PNI.
Asunto(s)
Tejido Adiposo , Traumatismos de los Nervios Periféricos , Adipocitos , Animales , Humanos , Ratones , Factores de Crecimiento Nervioso/metabolismo , Traumatismos de los Nervios Periféricos/metabolismo , Traumatismos de los Nervios Periféricos/terapia , Células de Schwann , Células MadreRESUMEN
The tumor microenvironment affects malignancy in hepatocellular carcinoma (HCC) cells, and cancer-associated fibroblasts (CAFs) play an important role in the microenvironment. As recent studies indicated a difference between CAFs isolated from chemoresistant and non-resistant cancer tissues, therefore we investigated the intracellular mechanism in resistant HCC co-cultured CAFs and interactions between these CAFs with cancer cells. We established a sorafenib-resistant (SR) Huh7 (human HCC) cell line, and characterized it with cytokine assays, then developed CAFs by co-culturing human hepatic stellate cells with resistant or parental Huh7 cells. The 2 types of CAFs were co-cultured with parental Huh7 cells, thereafter the cell viability of these Huh7 cells was checked under sorafenib treatment. The SR Huh7 (Huh7SR ) cells expressed increased B-cell activating factor (BAFF), which promoted high expression of CAF-specific markers in Huh7SR -co-cultured CAFs, showed activated BAFF, BAFF-R, and downstream of the NFκB-Nrf2 pathway, and aggravated invasion, migration, and drug resistance in co-cultured Huh7 cells. When we knocked down BAFF expression in Huh7SR cells, the previously increased malignancy and BAFF/NFκB axis in Huh7SR -co-cultured CAFs reversed, and enhanced chemoresistance in co-cultured Huh7 cells returned as well. In conclusion, the BAFF/NFκB pathway was activated in CAFs co-cultured with cell-culture medium from resistant Huh7, which promoted chemoresistance, and increased the malignancy in co-cultured non-resistant Huh7 cells. This suggests that the BAFF/NFκB axis in CAFs might be a potential therapeutic target in chemoresistance of HCC.
Asunto(s)
Antineoplásicos/farmacología , Factor Activador de Células B/metabolismo , Fibroblastos Asociados al Cáncer/metabolismo , Carcinoma Hepatocelular/metabolismo , Comunicación Celular/genética , Resistencia a Antineoplásicos/genética , Neoplasias Hepáticas/metabolismo , FN-kappa B/metabolismo , Transducción de Señal/genética , Sorafenib/farmacología , Factor Activador de Células B/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Movimiento Celular/genética , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/genética , Técnicas de Cocultivo , Resistencia a Antineoplásicos/efectos de los fármacos , Técnicas de Silenciamiento del Gen , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , TransfecciónRESUMEN
An 87-year-old woman was referred to our hospital with early rectal cancer and massive ascites. Tuberculous peritonitis was suspected because positron emission tomography-computed tomography showed high uptake in the hypertrophic peritoneum. A staging laparoscopy was performed and the diagnosis of tuberculous peritonitis was established from inspection of histopathological biopsy specimens showing tiny white nodules on the peritoneum, Langhans giant cells, and epithelioid cell granulomas. Tuberculosis bacterium was also detected from this tissue. After 4 months' treatment for tuberculous peritonitis, laparoscopy assisted low-anterior resection was performed. Laparoscopy was used to assess the status of tuberculous peritonitis from before to after treatment, and treatment for rectal cancer was instituted.