ES2537004T3 - Trasplante de células neurales humanas para el tratamiento de afecciones neurodegenerativas - Google Patents
Trasplante de células neurales humanas para el tratamiento de afecciones neurodegenerativas Download PDFInfo
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- ES2537004T3 ES2537004T3 ES05851748.3T ES05851748T ES2537004T3 ES 2537004 T3 ES2537004 T3 ES 2537004T3 ES 05851748 T ES05851748 T ES 05851748T ES 2537004 T3 ES2537004 T3 ES 2537004T3
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- 230000000626 neurodegenerative effect Effects 0.000 title 1
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- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/30—Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue
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- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
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Abstract
Un procedimiento in vitro para preparar una población de células madre neurales capaces de generar neuronas en una médula espinal del receptor que comprenda: a) expandir al menos una célula madre neural obtenida directamente del tejido de mamífero en un recipiente de cultivo recubierto previamente con 0,1 μg/ml a 1 mg/ml de uno o más polímeros capaces de promover la adhesión de las células; b) concentrar la población expandida, en el que la menos la célula madre neural se obtiene de fuentes de mamífero diferentes a embriones humano, en el que cultivar la célula madre neural en ausencia de suero, en el que expandir la célula madre neural incluye exponer la célula madre neural a al menos un factor de crecimiento y en el que la expansión celular excede las treinta duplicaciones de las células sin diferenciación.
Description
E05851748
14-05-2015
BREVE DESCRIPCIÓN DE LAS FIGURAS
5 Figura 1. Expansión de células madre neurales humanas. Se aisló una línea progenitora medular humana (conocida como CMN) de tejido de la médula espinal fetal post mortem de 7 a 8 semanas de edad y se pasó de forma seriada durante aproximadamente 130 días de periodo neto de cultivo. En cada pase, el número de células recuperadas en la recogida se dividió por el número inicial de células en la siembra en placa para obtener el número de veces de aumento en el número de células. El número de veces de aumento acumulado (eje Y izquierdo) se obtuvo
10 multiplicando el número de veces de aumento en cada pase. El tiempo de duplicación (eje Y derecho) de las células en cada pase se calculó dividiendo el número de veces de aumento del número de células por el periodo de cada cultivo (eje X). Este proceso se repitió tres veces (expansión seriada 1, 2 y 3).
Figura 2. Morfología de las células madre medulares humanas expandidas. (A) Vista con contraste de fases de un 15 cultivo en expansión fijado y sin teñir, objetivo 20x, (B) Tinción con anticuerpo anti-nestina.
Figura 3. Caracterización de los cultivos diferenciados obtenidos a partir de células madres medulares humanas. Las células expandidas de los pases 15-16 se diferenciaron durante aproximadamente 14 días de cultivo, se fijaron y tiñeron con diversos anticuerpos específicos de neuronas. (A) Tau y MAP2; (B) tubulina beta de tipo 3; (C) GABA;
20 (D) Acetilcolina transferasa.
Figura 4. Expansión de células madre de mesencéfalo humanas. Se aisló una línea progenitora de mesencéfalo humana (conocida como CMN) a partir de tejido de mesencéfalo fetal postmorten de 7-8 semanas y se pasó de forma seriada durante aproximadamente 170 días de periodo neto de cultivo. En cada pase, el número de células
25 recuperadas en la recogida se dividió por el número inicial de células en la siembra para obtener el número de veces de aumento en el número de células. El número de veces de aumento acumulado (eje Y) se obtuvo multiplicando el número de veces de aumento en cada pase.
Figura 5. Actividad de captación de dopamina de las células madre de mesencéfalo humano expandidas. La
30 actividad transportadora de dopamina (ATD) en células vivas se determinó a partir de una línea de células madre de mesencéfalo humano y una de sus sublíneas clonales, que se diferenciaron durante 22 o 44 días en el momento del ensayo. Las células se incubaron con dopamina marcada radiactivamente en presencia (+) o ausencia (-) del inhibidor de ATD nomifensina (10 µM). Las células se lavaron para eliminar la dopamina no incorporada y se lisaron en una mezcla de líquido de centelleo. A continuación, se determinó la radioactividad celular total (dpm) usando un
35 contador de centelleo.
Figura 6. Efecto de los factores exógenos sobre la inducción de diferenciación neuronal y diferenciación dopaminérgica de líneas celulares madre de mesencéfalo humanas. Las células madre neurales crioconservadas de dos lineas de células madre de mesencéfalo humanas (527RMB y 796RMB) se descongelaron y sembraron en 40 placas a una densidad de 40 000 células por pocillo en portaobjetos de cuatro cámaras en presencia de bFGF y se dejó que proliferaran durante 6 días. Posteriormente, se retiró el bFGF y se permitió la diferenciación durante 8 días más. Las células se dividieron en cuatro grupos en función del tiempo y duración de la exposición a medio acondicionado con células de Sertoli (SCCM, diluido 1:1 en N2). Un grupo se expuso a SCCM durante la proliferación y diferenciación (condición 1); un segundo grupo se expuso solo durante la proliferación (condición 2); 45 un tercero se expuso solo durante la diferenciación (condición 3) y un cuarto no se expuso a SCCM (Control, Cont.). Los medios se cambiaron cada dos días, y se añadió un mitógeno diariamente durante la fase proliferativa. Se mantuvieron cuatro pocillos por condición para poder realizar un marcaje con múltiples marcadores. Tras la diferenciación, las células se fijaron usando paraformaldehído al 4% y se realizó una inmunotinción usando anticuerpos frente a MAP2ab (Fig. 6A) y tirosina hidroxilasa (Fig. 6B), así como GFAP y GalC. Las células
50 inmunoteñidas se contaron usando un objetivo 40x y se contaron al menos tres campos para cada pocillo. Se detectaron pocas o ninguna célula GFAP+ o GalC+ tras el análisis de células mantenidas en cualquier condición, por lo que estos antígenos se excluyeron del análisis.
Figura 7. Reducción de la espasticidad/rigidez y de las deficiencias motoras en ratas mediante trasplante de células
55 madre neurales humanas. Se obtuvieron ratas espásticas mediante lesión isquémica de la médula espinal lumbar. En un grupo (círculos negros), las ratas (n = 9) se trasplantaron con células madre medulares humanas expandidas en cultivo (pase 16), mientras que el otro grupo, el grupo control (círculos blancos, n = 7) recibieron solo los medios sin las células. El agente inmunosupresor FK506 se administró a 1 mg/kg al día a ambos grupos durante todo el estudio (8 semanas). La coordinación motora de animales individuales se evaluó mediante la puntuación BBB una
9
Claims (1)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US62922004P | 2004-11-17 | 2004-11-17 | |
| US629220 | 2004-11-17 | ||
| PCT/US2005/041631 WO2006055685A2 (en) | 2004-11-17 | 2005-11-17 | Transplantation of human neural cells for treatment of neurodegenerative conditions |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2537004T3 true ES2537004T3 (es) | 2015-06-01 |
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ID=36407743
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES05851748.3T Active ES2537004T3 (es) | 2004-11-17 | 2005-11-17 | Trasplante de células neurales humanas para el tratamiento de afecciones neurodegenerativas |
Country Status (13)
| Country | Link |
|---|---|
| US (6) | US7691629B2 (es) |
| EP (2) | EP2913393B8 (es) |
| JP (3) | JP5424559B2 (es) |
| KR (2) | KR101429284B1 (es) |
| CN (2) | CN101084303A (es) |
| ES (1) | ES2537004T3 (es) |
| HK (1) | HK1202238A1 (es) |
| IL (2) | IL183092A (es) |
| IN (1) | IN2014CN03629A (es) |
| NO (1) | NO340914B1 (es) |
| PH (1) | PH12015501195B1 (es) |
| RU (2) | RU2434636C2 (es) |
| WO (1) | WO2006055685A2 (es) |
Families Citing this family (44)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7838292B1 (en) | 2001-03-29 | 2010-11-23 | University Of Louisville Research Foundation, Inc. | Methods for obtaining adult human olfactory progenitor cells |
| US9592258B2 (en) | 2003-06-27 | 2017-03-14 | DePuy Synthes Products, Inc. | Treatment of neurological injury by administration of human umbilical cord tissue-derived cells |
| US9572840B2 (en) | 2003-06-27 | 2017-02-21 | DePuy Synthes Products, Inc. | Regeneration and repair of neural tissue using postpartum-derived cells |
| US8491883B2 (en) * | 2003-06-27 | 2013-07-23 | Advanced Technologies And Regenerative Medicine, Llc | Treatment of amyotrophic lateral sclerosis using umbilical derived cells |
| RU2434636C2 (ru) | 2004-11-17 | 2011-11-27 | Ньюралстем, Инк. | Трансплантация нервных клеток для лечения нейродегенеративных состояний |
| AU2006220696B2 (en) | 2005-03-07 | 2010-08-19 | Sanbio, Inc. | Use of neuronal precursor cells for treatment of central nervous system lesions |
| GB0822246D0 (en) | 2008-12-05 | 2009-01-14 | Reneuron Ltd | Composition |
| BRPI0923177A2 (pt) * | 2008-12-19 | 2020-08-25 | Advanced Technologies And Regenerative Medicine, Llc | usos de composições para tratar dor neuropática e espacidade, as referidas composições, e kit |
| CA2747794C (en) | 2008-12-19 | 2018-10-30 | Advanced Technologies And Regenerative Medicine, Llc | Treatment of lung and pulmonary diseases and disorders |
| GB0902034D0 (en) | 2009-02-06 | 2009-03-11 | Reneuron Ltd | Method |
| US10386360B2 (en) | 2009-03-13 | 2019-08-20 | University Of Central Florida Research Foundation, Inc. | Bio-microelectromechanical system transducer and associated methods |
| CA2756600C (en) | 2009-03-26 | 2019-08-20 | Advanced Technologies And Regenerative Medicine, Llc | Human umbilical cord tissue cells as therapy for alzheimer's disease |
| US8815584B1 (en) | 2009-04-23 | 2014-08-26 | University Of Central Florida Research Foundation, Inc. | Method of co-culturing mammalian muscle cells and motoneurons |
| US9163216B1 (en) | 2009-04-23 | 2015-10-20 | University Of Central Florida Research Foundation, Inc. | Method for culturing skeletal muscle for tissue engineering |
| US8828721B1 (en) | 2009-05-28 | 2014-09-09 | University Of Central Florida Research Foundation, Inc. | Method of myelinating isolated motoneurons |
| US9404140B1 (en) | 2009-11-03 | 2016-08-02 | The University Of Central Florida Research Foundation, Inc. | Patterned cardiomyocyte culture on microelectrode array |
| US9489474B2 (en) | 2010-02-05 | 2016-11-08 | University Of Central Florida Research Foundation, Inc. | Model and methods for identifying points of action in electrically active cells |
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