RESUMEN
Decellularization of pancreata and repopulation of these non-immunogenic matrices with islets and endothelial cells could provide transplantable, endocrine Neo- Pancreata. In this study, rat pancreata were perfusion decellularized and repopulated with intact islets, comparing three perfusion routes (Artery, Portal Vein, Pancreatic Duct). Decellularization effectively removed all cellular components but conserved the pancreas specific extracellular matrix. Digital subtraction angiography of the matrices showed a conserved integrity of the decellularized vascular system but a contrast emersion into the parenchyma via the decellularized pancreatic duct. Islets infused via the pancreatic duct leaked from the ductular system into the peri-ductular decellularized space despite their magnitude. TUNEL staining and Glucose stimulated insulin secretion revealed that islets were viable and functional after the process. We present the first available protocol for perfusion decellularization of rat pancreata via three different perfusion routes. Furthermore, we provide first proof-of-concept for the repopulation of the decellularized rat pancreata with functional islets of Langerhans. The presented technique can serve as a bioengineering platform to generate implantable and functional endocrine Neo-Pancreata.
Asunto(s)
Bioingeniería , Islotes Pancreáticos/fisiología , Regeneración , Andamios del Tejido , Animales , Biomarcadores , Supervivencia Celular , Matriz Extracelular , Femenino , Supervivencia de Injerto , Inmunohistoquímica , Islotes Pancreáticos/citología , Islotes Pancreáticos/ultraestructura , Masculino , RatasRESUMEN
The frequency of delayed function of kidney transplants varies greatly and is associated with quality of graft, donor age and the duration of cold ischemia time. Furthermore, body weight differences between donor and recipient can affect primary graft function, but the underlying mechanism is poorly understood. We transplanted kidney grafts from commensurate body weight (L-WD) or reduced body weight (H-WD) donor rats into syngeneic or allogeneic recipients. Twenty-four hours posttransplantation, serum creatinine levels in H-WD recipients were significantly higher compared to L-WD recipients indicating impaired primary graft function. This was accompanied by upregulation of IL-6 transcription and increased tubular destruction in grafts from H-WD recipients. Using DNA microarray analysis, we detected decreased expression of genes associated with kidney function and an upregulation of other genes such as Cyp3a13, FosL and Trib3. A single application of IL-6 into L-WD recipients is sufficient to impair primary graft function and cause tubular damage, whereas immediate neutralization of IL-6 receptor signaling in H-WD recipients rescued primary graft function with well-preserved kidney graft architecture and a normalized gene expression profile. These findings have strong clinical implication as anti-IL6R treatment of patients receiving grafts from lower-weight donors could be used to improve primary graft function.
Asunto(s)
Peso Corporal/fisiología , Interleucina-6/fisiología , Trasplante de Riñón/fisiología , Transducción de Señal/fisiología , Animales , Apoptosis/fisiología , Creatinina/sangre , Hemo-Oxigenasa 1/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Trasplante de Riñón/patología , Túbulos Renales/patología , Masculino , Modelos Animales , Ratas , Ratas Endogámicas Lew , Ratas EndogámicasAsunto(s)
Sueños , Factores Sexuales , Adolescente , Adulto , Femenino , Humanos , Masculino , Recuerdo Mental , SexoRESUMEN
Measured differences in the ability of paraprofessionals to discriminate and communicate facilitative conditions in psychotherapy as a function of length of experience. Hypothesis tested were that discrimination and communication abilities would be greater in Ss with longer experience and that these abilities would be correlated positively within individuals. Thirty-six mental health workers were categorized into three levels of experience and initial competency. Ss were administered the Carkhuff Discrimination Rating Scale; the level of conditions communicated to patients was assessed through replies to taped patient interviewers. Results failed to support the hypothesized relationships between functioning and experience. However, several interactions were found. Initially more competent Ss tended to improve over time and less competent Ss declined. A positive correlation between abilities within individuals was found. Results were compared with studies that measured the functioning of professional psychology trainees over time, are relevant to issues of therapist selection, and support the use of experiential training programs.