Efecto de la inyección de celulas troncales mesenquimáticas en un modelo de insuficiencia renal crónica
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Fecha
2008
Profesor/a Guía
Facultad/escuela
Idioma
es
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Universidad Andrés Bello
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Licencia CC
Licencia CC
Resumen
La Insuficiencia Renal Crónica (IRC) se define como la pérdida progresiva e irreversible de la
funcionalidad renal, ésta se inicia con la disminución del volumen de filtración glomerular
debido al daño del nefrón, progresa con trastornos en la homeostasis debido al daño tubular y
finalmente produce una falla en la función hormonal del riñón. Actualmente no existen
estrategias terapéuticas capaces de revertir el daño inducido crónicamente, ni estudios destinados
a evaluar en este modelo, el potencial regenerador del riñón. No obstante, se sabe que en la
Insuficiencia Renal Aguda (IRA), puede existir recuperación funcional de los nefrones dañados;
en la IRA se ha demostrado que ante un daño isquémico, las células renales pueden re-expresar
un conjunto de nefrogenes y moléculas angiogénicas, que normalmente están presentes en el
desarrollo embrionario, donde cumplen importantes funciones epiteliogénicas y tubulogénicas.
El riñón adulto carece de ellas. Estos resultados proponen que la re-expresión secuencial de genes
nefrogénicos, participaría en la regeneración del tejido dañado.
Las Células Troncales Mesenquimáticas (CTM) se caracterizan por su capacidad de autorenovarse
y diferenciarse en distintos tipos celulares. Recientes estudios han demostrado que la
administración exógena de CTM favorece la recuperación de IRA inducida experimentalmente
mediante isquemia/reperfusión (I/R), corroborando que el epitelio tubular del adulto tiene el
potencial regenerador luego de inducido un daño agudo. Así, células tubulares pueden
experimentar desdiferenciación y reobtener su potencial mitótico. Estudios similares durante el
desarrollo de la IRC no han sido realizados.
El objetivo de este estudio es, por lo tanto, evaluar la eficacia terapéutica de CTM derivadas de
la médula ósea en un modelo de IRC establecido y evaluar la expresión de proteínas nefrogénicas
como indicador de reparación renal. El daño funcional se analizó evaluando los niveles de
creatinina plasmática, la determinación de los marcadores de daño renal se analizó mediante
inmunohistoquímica y la expresión de proteínas nefrogénicas se estudió mediante la técnica de
Western blot. Los resultados obtenidos sugieren que la administración exógena de CTM podría
inducir la reparación en la IRC, mediante nefrogenes renales.
The chronic renal failure (CRF) is defined as the progressive and irreversible loss of kidney function; it starts with the declining volwne of glomerular filtration due to the damage of the nephron, progressing with disorders in the homeostasis dueto injury and finally produces tubular a flaw in the hormonal function of the kidney. There are currently no therapeutic strategies able to reverse the damage induced chronically or studies to assess in this model, the regenerative potential of the kidney. However, it is known that in acute renal failure (ARF), there may be functional recovery of the nephron damaged in ARF has shown that before an ischemic damage, kidney cells can re-express a set of angiogenic molecules and nephrogenic protein, which is normally present in embryonic development, where they serve important functions epiteliogénicas and tubulogénicas. The kídney adult lacks them. These results suggest that the sequential re-expression of nephrogenic protein, would participate in the regeneration of tissue damaged. The mesenchymal Stem Cell (MSC) is characterized by their ability to self-renew and differentiate into different cell types. Recent studies have shown that exogenous administration of MSC promotes the recovery of experimental ARF induced by ischemia 1 reperfusion (I/R), corroborating that the tubular epithelium of the adult has the potential of regenerating after acute injury. Thus, tubular cells may experience des-differentiation and acquire mitotic potential. Similar studies for the development of the CRF ha ve not bee show. The aím of this study is assess the therapeutic efficacy of MSC derived from bone marrow in a model of ARF set, and evaluate the expression of nephrogenic proteins as an indicator of renal repair. The functional damage was analyzed to assess the levels of serwn creatiníne markers of kidney damage were analyzed using immunohistochemistry and the expression of nephrogenic proteins was studied by Westem blot. These results suggest that administration of exogenous MSC could induce regeneration m CRF, through nephrogenic proteins.
The chronic renal failure (CRF) is defined as the progressive and irreversible loss of kidney function; it starts with the declining volwne of glomerular filtration due to the damage of the nephron, progressing with disorders in the homeostasis dueto injury and finally produces tubular a flaw in the hormonal function of the kidney. There are currently no therapeutic strategies able to reverse the damage induced chronically or studies to assess in this model, the regenerative potential of the kidney. However, it is known that in acute renal failure (ARF), there may be functional recovery of the nephron damaged in ARF has shown that before an ischemic damage, kidney cells can re-express a set of angiogenic molecules and nephrogenic protein, which is normally present in embryonic development, where they serve important functions epiteliogénicas and tubulogénicas. The kídney adult lacks them. These results suggest that the sequential re-expression of nephrogenic protein, would participate in the regeneration of tissue damaged. The mesenchymal Stem Cell (MSC) is characterized by their ability to self-renew and differentiate into different cell types. Recent studies have shown that exogenous administration of MSC promotes the recovery of experimental ARF induced by ischemia 1 reperfusion (I/R), corroborating that the tubular epithelium of the adult has the potential of regenerating after acute injury. Thus, tubular cells may experience des-differentiation and acquire mitotic potential. Similar studies for the development of the CRF ha ve not bee show. The aím of this study is assess the therapeutic efficacy of MSC derived from bone marrow in a model of ARF set, and evaluate the expression of nephrogenic proteins as an indicator of renal repair. The functional damage was analyzed to assess the levels of serwn creatiníne markers of kidney damage were analyzed using immunohistochemistry and the expression of nephrogenic proteins was studied by Westem blot. These results suggest that administration of exogenous MSC could induce regeneration m CRF, through nephrogenic proteins.
Notas
Tesis (Tecnólogo Médico)
Palabras clave
Insuficiencia Renal Crónica, Células Madre