{"id":117054,"date":"2018-03-11T10:46:27","date_gmt":"2018-03-11T10:46:27","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/estudio-sobre-la-seguridad-del-constructo-de-celulas-mesenquinales-fosfato-tricalcico-y-matriz-osea-desmineralizada-para-uso-cla%c2%adnico\/"},"modified":"2018-03-11T10:46:27","modified_gmt":"2018-03-11T10:46:27","slug":"estudio-sobre-la-seguridad-del-constructo-de-celulas-mesenquinales-fosfato-tricalcico-y-matriz-osea-desmineralizada-para-uso-cla%c2%adnico","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/cirugia-de-trasplantes\/estudio-sobre-la-seguridad-del-constructo-de-celulas-mesenquinales-fosfato-tricalcico-y-matriz-osea-desmineralizada-para-uso-cla%c2%adnico\/","title":{"rendered":"Estudio sobre la seguridad del constructo de c\u00e9lulas mesenquinales, fosfato tric\u00e1lcico y matriz \u00f3sea desmineralizada para uso cl\u00ednico."},"content":{"rendered":"<h2>Tesis doctoral de <strong> Mar\u00eda  Del Mar Gonzalvez Garcia <\/strong><\/h2>\n<p>Comprobar la seguridad y valorar la eficacia del uso del constructo formado por c\u00e9lulas mesenquimales de m\u00e9dula \u00f3sea humana (msc) sembradas y cultivadas sobre matriz po-rosa de fosfato tric\u00e1lcico (ftc) asociadas a matriz \u00f3sea desmineralizada (mod) implantada en en ratones inmunodeprimidos nod\/scid.  objetivos espec\u00edficos: estudiar la toxicidad aguda y cr\u00f3nica del implante (ftc+msc+mod) en modelo murino nod\/scid.  estudiar la biodistribuci\u00f3n del constructo (ftc+msc+mod) implantado en modelo murino nod\/scid.  valorar si hay formaci\u00f3n de tejido \u00f3seo en el lugar del implante en el rat\u00f3n nod\/scid del constructo (ftc+msc+mod). valorar a partir de que momento se observa formaci\u00f3n \u00f3sea en el lugar del implante en el rat\u00f3n nod\/scid del constructo (ftc+msc+mod).  metodolog\u00eda: estudio prospectivo anal\u00edtico con 30 ratones nod\/scid divididos en 2 grupos de ensayo. el grupo experimental, de 25 ratones, se implanta subcut\u00e1nea e intramuscularmente un constructo formado por c\u00e9lulas madre mesenquimales humanas sembradas en fosfato tric\u00e1lcico mezcladas con matriz \u00f3sea desmineralizada (msc+ftc+mod). En el segundo grupo, control, de 5 ratones se implanta de forma an\u00e1loga el constructo formado por suero salino fisiol\u00f3gico al 0,9%, fosfato tric\u00e1lcico y matriz \u00f3sea desmineralizada (ssf 0,9%+ftc+mod). los ratones del primer grupo fueron sacrificados por parejas de macho y hembra a las 24h, a las 48h, a la semana, a las 2, 5, 7 y 9 semanas tras la cirug\u00eda. Los ratones del segundo grupo y los 11 ratones restantes del primer grupo se sacrificaron a las 12 semanas. se ha evaluado la toxicidad aguda, a las 24 y 48 horas tras la cirug\u00eda, mediante el control del peso, el \u00edndice de bienestar animal, an\u00e1lisis sangu\u00edneo, bioqu\u00edmico y estudios histol\u00f3gicos de los \u00f3rganos: h\u00edgado, pulm\u00f3n, bazo, cerebro, ri\u00f1\u00f3n, coraz\u00f3n, g\u00f3nadas, m\u00e9dula \u00f3sea y hueso.  la toxicidad cr\u00f3nica fue evaluada mediante los mismos estudios que en fase aguda sacrificando 2 ratones en la 1\u00aa, 2\u00aa, 5\u00aa, 7\u00aa, 9\u00aa semana, once ratones en la 12\u00aa semana y los 5 ratones del 2\u00c2\u00ba grupo. para evaluar la biodistribuci\u00f3n del constructo se realiz\u00f3 an\u00e1lisis pcr-rt de 2 prote\u00ednas, la actina y la ?2microglobulina a h\u00edgado, pulm\u00f3n, bazo, cerebro, ri\u00f1\u00f3n, coraz\u00f3n, g\u00f3nadas, m\u00e9dula \u00f3sea y de la sangre perif\u00e9rica de cada rat\u00f3n sacrificado. para valorar la eficacia se realizaron estudios histol\u00f3gicos del constructo implantado con hematoxilina-eosina, tricr\u00f3mico de masson y estudios inmunohistoqu\u00edmicos cualitativos y cuantitativos con anticuerpos anti-osteocalcina.                 resultados o conclusiones el implante subcut\u00e1neo o intramuscular del constructo ftc+msc+mod no ha mostrado signos de toxicidad aguda o cr\u00f3nica en el modelo murino nod\/scid. tras la implantaci\u00f3n del constructo ftc+msc+mod implantado de forma subcut\u00e1nea o intramuscular en el modelo murino nod\/scid no han sido halladas c\u00e9lulas mesenquima-les humanas en ning\u00fan \u00f3rgano. Permaneciendo las c\u00e9lulas en el lugar del implante. no se han observado diferencias estad\u00edsticamente significativas entre el poder osteog\u00e9ni-co del constructo ftc+msc+mod. Aunque si existen entre el poder osteog\u00e9nico del im-plante subcut\u00e1neo e intramuscular.   la formaci\u00f3n de tejido \u00f3seo estructurado se ha observado a partir de la semana 7 en la zona de implante subcut\u00e1nea y a partir de la semana 9 en la zona de implante intramus-cular.    to check the security and assess the effectiveness, of the use of mesenchymal cells of human bone marrow (msc) seeded and cultured on tricalcium phosphate porous matrix (ftc) associated with demineralized bone matrix (mod) implanted in immunosuppressed mice nod\/scid. specific objectives: to study the acute and chronic toxicity of the implant (ftc+msc+mod) construct in muri-ne nod\/scid model. to study the biodistribution of the implant (ftc+msc+mod) construct in murine nod\/scid model. to evaluate the formation of bone tissue at the site of the (ftc+msc+mod) construct im-plant. to evaluate the cronology of bone tissue formation at the site of the (ftc+msc+mod) construct implant.  methodology analytical prospective study with 30 nod\/scid mice divided into 2 treatment groups was  performed. in the first group of 25 mice, a construct of mesenchymal stem cells seeded and cultured on tricalcium phosphate porous matrix and associated with demineralized bone matrix (msc+ftc+mod)  was implanted subcutaneously and intramuscularly  in the second group of 5 mice, a construction of 0,9% saline, matrix porous tricalcium phosphate associated with demineralized bone matrix (ssf0,9%+ftc+mod)  was im-planted also subcutaneously and intramuscularly  male and female mice pairs of the first group were &#8211; sacrificed at 24 h, 48 h, 1 week  and then 2,5,7 and 9 weeks after surgery. The second group of mice and the 11 remaining mice of the first group were sacrificed at 12 weeks. acute toxicity was evaluated by the assessment of &#8211; weight, the animal welfare score, blood and biochemical analysis and histological studies of organs: liver, lung, spleen, brain, kidney, heart, gonads, bone marrow and bone of each mouse sacrificed in the first 48h after surgery. chronic toxicity was evaluated by the same studies sacrificing 2 mice in the 1st, 2nd, 5th, 7th and 9th week, eleven mice in the 12 th week, and the remaining 5 of the second group. biodistribution of the construct was analysed by rt-pcr test of 2 proteins, actin and the ?2microglobulin of liver, lung, spleen, brain, kidney, heart, gonads, bone marrow and pe-ripheral blood from each mouse sacrificed. effectiveness was evaluated at implanted site by qualitative and quantitative studies im-munohistochemistry with anti-osteocalcin antibodies and histological studies with hema-toxylin-eosin, masson&apos;s trichrome were performed.  conclusions construct (ftc+msc+mod) implanted via subcutaneous or intramuscular has not pre-sented any signs of acute or chronic toxicity in the mouse model nod \/ scid. human mesenchymal stem cells have not been found in any organ analyzed at murine model of construct (ftc+msc+mod) implanted subcutaneously or intramuscularly . These have remained at the implant site. no statistically significant differences were observed between the osteogenic power of the construct msc + ftc + mod. However, it has definetely been found between subcutane-ous and intramuscular implant. structured bone formation is observed from week 7 in the subcutaneous implant and from week 9  in the intramuscular implant.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Estudio sobre la seguridad del constructo de c\u00e9lulas mesenquinales, fosfato tric\u00e1lcico y matriz \u00f3sea desmineralizada para uso cl\u00ednico.<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Estudio sobre la seguridad del constructo de c\u00e9lulas mesenquinales, fosfato tric\u00e1lcico y matriz \u00f3sea desmineralizada para uso cl\u00ednico. <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Mar\u00eda  Del Mar Gonzalvez Garcia <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Murcia<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 23\/01\/2015<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h3>Direcci\u00f3n y tribunal<\/h3>\n<ul>\n<li><strong>Director de la tesis<\/strong>\n<ul>\n<li>villaca\u00f1as Marin Fernandez<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: gin\u00e9s Dom\u00e9nech ratto <\/li>\n<li>salvador Mart\u00ednez p\u00e9rez (vocal)<\/li>\n<li>Jos\u00e9 Mar\u00eda Moraleda jim\u00e9nez (vocal)<\/li>\n<li>Miguel Puche torres (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Mar\u00eda Del Mar Gonzalvez Garcia Comprobar la seguridad y valorar la eficacia del uso del constructo formado 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