abril 2012 Archives

Investigadores del Hospital Infantil de Filadelfia (Estados Unidos) han generado un nuevo tipo de células madre humanas que pueden dar lugar a diversas clases de células especializadas, como las células beta productoras de insulina. Su estudio se publica en el último número de Cell Stem Cell (Doi: 10.1016/j.stem.2012.02.024).

Las denominadas células progenitoras endodérmicas presentan, según Paul Gadue y sus colaboradores, importantes ventajas respecto a las células madre embrionarias y las células pluripotenciales inducidas (iPS): no generan tumores cuando se trasplantan a animales y con ellas se pueden generar células beta pancreáticas funcionales.

También consiguieron diferenciarlas en células hepáticas e intestinales. Ambas se generan a partir del tejido endodérmico en las primeras fases del desarrollo humano.

El nuevo tipo de células madre se obtuvo a partir tanto de células madre embrionarias como de iPS, utilizando citocinas para inducir la diferenciación en células endodérmicas.

El equipo demostró el potencial de estas células en cultivos celulares y en experimentos con animales. Además, constató que no formaban teratomas cuando se trasplantaban.

Producción de insulina
Las células beta en que se diferenciaron las nuevas progenitoras fueron capaces de secretar insulina cuando eran estimuladas mediante glucosa. Los investigadores creen que se trata de un logro importante, a pesar de que las células solo alcanzaron un 20 % de su funcionamiento normal. Otras células derivadas a partir de células madre embrionarias o iPS responden mucho peor a la glucosa.

El siguiente paso será obtener estas células de pacientes con formas genéticas de diabetes o de enfermedades hepáticas para obtener líneas celulares que sirvan como modelo de estudio de estas enfermedades.
abril 8/2012 (Diario Médico)

Henry C. Lin, Darrell N. Kotton, Steven S. Shen, M. Cristina Nostro, John Kim Choi, Mitchell J. Weiss, et. al. Self-Renewing Endodermal Progenitor Lines Generated from Human Pluripotent Stem Cells. Cell Stem Cell: vol 10(4), 371-384, abril 6/2012.

En: Noticias #

The potential use of stem cell-based therapies for the repair and regeneration of various tissues and organs offers a paradigm shift that may provide alternative therapeutic solutions for a number of diseases. The use of either embryonic stem cells (ESCs) or induced pluripotent stem cells in clinical situations is limited due to cell regulations and to technical and ethical considerations involved in the genetic manipulation of human ESCs, even though these cells are, theoretically, highly beneficial. Mesenchymal stem cells seem to be an ideal population of stem cells for practical regenerative medicine, because they are not subjected to the same restrictions. In particular, large number of adipose-derived stem cells (ASCs) can be easily harvested from adipose tissue. Furthermore, recent basic research and preclinical studies have revealed that the use of ASCs in regenerative medicine is not limited to mesodermal tissue but extends to both ectodermal and endodermal tissues and organs, although ASCs originate from mesodermal lineages. Based on this background knowledge, the primary purpose of this concise review is to summarize and describe the underlying biology of ASCs and their proliferation and differentiation capacities, together with current preclinical and clinical data from a variety of medical fields regarding the use of ASCs in regenerative medicine. In addition, future directions for ASCs in terms of cell-based therapies and regenerative medicine are discussed.
Acceso directo a trevés del HINARI

STEM CELLS2012;30:804–810

Stem cells: Don’t believe the hype
Michael Eisenstein
Journal name: Nature .Volume: 484, Page: S5 Date published: (12 April 2012)
DOI: doi:10.1038/nature11107 Published online 11 April 2012

Researchers are still a long way from using stem cells to halt the decline caused by multiple sclerosis and to restore patients’ health. But they are following some promising trails.

The remarkable potential of stem cells to develop into healthy adult tissue has led many people to view them as a biomedical ‘Wizard of Oz’, ready to grant them a healthy new heart or brain on demand. This perception has been fuelled by feverish media coverage extolling their vast therapeutic potential. But as with the great and powerful Oz, misconceptions abound. The capabilities of current therapies are sometimes overstated, and some patients with serious degenerative disorders such as multiple sclerosis (MS) are disappointed once they peer behind the curtain.

“Most of the patients that come to us ask me to give them stem cells because they want to walk again,” says Antonio Uccelli, a neuroimmunologist who performs clinical stem-cell research at Italy’s University of Genoa. “Patients are mesmerized by the hope that stem-cell treatment is a treatment for regenerating tissue, and it’s difficult to convince them otherwise.”

Anthony Uccelli, U of Genoa

Embryonic stem (ES) cells, which can transform into any cell in the body, might one day offer this potential. But ES cells are only slowly making their way into clinical trials, in part because research has been bogged down by strict regulations arising from the debate over the ethics of using material derived from human embryos. A more promising route for MS treatment involves various kinds of adult stem cells, which can develop into a much more limited range of cell types but nevertheless seem to exert far-reaching effects on both the immune system and the natural repair mechanisms in the central nervous system. Early studies suggest that adult stem cells might offer a way to halt the progression of therapy-resistant MS, even if the goal of reversing the existing damage remains over the horizon.

Resetting the system
In MS, the immune system attacks the central nervous system, stripping neurons of the protective myelin sheaths that insulate their axons and allow effective signal transmission. Stem cells offer the promise of essentially rebooting the immune system, thereby eradicating this autoimmune response. There is a precedent for this therapeutic approach. More than 25 years ago, Richard Burt, an immunotherapy researcher at Northwestern University in Chicago, Illinois, was inspired by outcomes he observed with leukaemia patients undergoing myeloablative treatment — the use of radiation and chemicals to wipe out the body’s capacity for blood-cell production — followed by a transplant of healthy bone marrow. These treatments were spectacularly effective at resetting the immune system. “Patients would come back after transplants and have to be reimmunized for childhood vaccines — measles, mumps, rubella and things like that,” says Burt. “It occurred to me that this is exactly what you want to happen with an autoimmune disease.”

Since then, Burt and others have demonstrated the therapeutic potential of haematopoietic stem-cell transplantation (HSCT) for MS and other conditions. In HSCT, blood-cell precursors (HSCs) are purified from a patient’s own bone marrow. The patient then undergoes a ‘conditioning’ chemotherapy regimen that heavily suppresses or even wipes out their defective immune system. The stem cells are then transplanted intravenously back into the patient, restoring immunity. The results have been remarkable: in many studies at least 60–70% of transplant recipients achieved relief from MS progression, and it seemed to last far beyond the initial treatment1. “In 10 years, we have never seen a renewal of inflammatory disease activity in any of our successfully treated patients,” says Mark Freedman, a neurologist at the University of Ottawa in Canada who has extensive experience of HSCT clinical trials.

Burt says his team has observed not only a halt in deterioration, but also, in several transplant recipients, quantifiable improvements in motor and cognitive function. Some studies suggest that implanted stem cells might facilitate repair by localizing to damaged nervous-system tissues, but other scientists believe that any recovery is simply the result of relief from the immune onslaught. “The signs are quite encouraging that once you stop the immune system in its tracks, the brain’s own repair capacity is able to manifest itself,” says neuroscientist Charles ffrench-Constant of the University of Edinburgh in the United Kingdom.

Practitioners see HSCT as a powerful way to help patients with aggressive forms of MS that have been resistant to standard drug regimens. But it is not a therapy to be taken lightly. Severe side effects include loss of hair and fingernails, as well as premature menopause for female patients. “The regimen that we use is completely myeloablative — it’s a standard bone-marrow transplant, and it’s no cakewalk,” says Freedman, “but the trade-off is years and years of not needing therapy.” Burt’s group has instead opted for a more moderate conditioning regimen that does not completely eradicate the patient’s bone marrow. Results suggest that this gentler approach can reduce the toxic effects of treatment without significantly undermining its efficacy2.

Repairing the damage
Other types of stem cell might offer a more palatable option for patients with less aggressive or less advanced disease. Gianvito Martino of the San Raffaele Scientific Institute in Milan, Italy, began working in mouse models of MS using neural precursor cells (NPCs), the stem cells that give rise to brain tissue. Martino hoped that the NPCs might penetrate brain lesions and turn into cells called oligodendrocytes, which can apply new layers of myelin to damaged cells.

Success was limited. “We didn’t find that those cells differentiate into myelin-forming cells, but they still had apparent curative potential,” Martino explains. “It turned out that they were capable of remaining undifferentiated, and still produced a whole bunch of substances that are neuroprotective.” His team termed this the ‘bystander effect’, whereby NPCs secrete signals that calm the immune system and promote natural processes of neuronal regeneration and remyelination. ffrench-Constant, who has studied myelination extensively, suggests that such strategies for reawakening the brain’s resident stem cells might be the best way to achieve effective repair in many MS patients. His team has identified several molecules that might stimulate the differentiation of existing precursor cells into active oligodendrocytes.

One clear advantage of NPCs is that they are operating in their natural surroundings. “They’re not only in the brain to replace the cells that you lose, they’re also there to keep that microenvironment in a healthy state,” says Martino. Although no clinical trials are currently underway for MS, researchers are closely watching a phase I trial being conducted by a company called StemCells in Palo Alto, California, to test the safety of transplanting fetal tissue-derived NPCs into young children with a congenital myelin deficiency disorder called Pelizaeus–Merzbacher disease. “The problem with MS cell therapy is that you’re transplanting cells into an adult nervous system that’s been damaged,” says ffrench-Constant. “If these cells don’t myelinate effectively in the developing brains of these children, it’s going to be exceptionally hard to get them to myelinate in the MS-affected adult CNS, where the hurdles are so much higher.”

Even if the NPCs are successful in remyelinating the damaged neurons, they will still face another problem. They are derived from donated fetal tissue and so carry a risk of host rejection, which means that recipients will need to be given immunosuppressant drugs. However, there is another, remarkably abundant reservoir of stem cells that might offer many of the same therapeutic benefits as fetal NPCs but with the safety and simplicity of transplanting someone’s own cells.

Joining forces
Mesenchymal stem cells (MSCs), which normally develop into fat, bone and connective tissue, are typically found in the bone marrow. However, they might also exert long-range, beneficial bystander effects, and have been examined as a possible therapy for a variety of autoimmune and other conditions. Once injected into MS patients, MSCs appear to migrate far and wide within the body, focusing on sites of tissue damage and even penetrating the central nervous system. However, their residence there seems to be brief, with therapeutic efficacy arising largely from the same bystander effect observed with NPCs. “Engraftment in the central nervous system is very limited and probably extremely transient,” says Uccelli. “It would be very difficult to believe that this 1–2% of cells [that reach the central nervous system] can justify the significant and clear evidence of improvement that we observe.”

Although formal demonstrations of efficacy in humans are lacking, studies in mouse models have given cause for hope. “If you administer [MSCs] early on, the recovery of the animals tends to be fairly enhanced,” says Freedman. A team led by neuroscientist Robert Miller of Case Western Reserve University in Cleveland, Ohio, has even demonstrated that administering human MSCs in the commonly used experimental autoimmune encephalomyelitis (EAE) mouse model can actively promote the growth and activation of myelin-repairing oligodendrocyte precursors within the brain3.

“MSCs are probably not as good at intense immunosuppression as the [HSC] treatment, but at least in animal studies, it’s been demonstrated that the ability of MSCs to foster repair is certainly much stronger,” says Uccelli. Although such stem-cell therapy is unlikely to displace front-line immunotherapeutics, it might offer a promising middle-ground therapy before committing to the rigours of HSCT. “There’s no bone-marrow suppression or chemo poisons, you’re simply putting in a cell product,” says Freedman, “and since they don’t get rejected, you don’t need anti-rejection medicine.”

There are roughly half a dozen phase I clinical trials underway to assess the safety of MSCs and perhaps glean some insight as to whether they might ameliorate symptoms. A recent study offers some early signs of hope, describing a small trial by scientists at the University of Cambridge in the United Kingdom, which showed no adverse effects in 10 patients treated with marrow-derived autologous MSCs4. The study also reports some signs of improvement in visual symptoms, although it is impossible to draw meaningful conclusions without a larger-scale, randomized, controlled trial. Indeed, issues of scale represent a broader problem for the handful of clinical trials on stem-cell MS therapy that have been completed to date. “What happens with stem-cell studies is that there are three patients here, three patients there, and at the end of the day it’s too few to draw any conclusions,” says Martino.

Even with HSCT, which has been successfully performed in several hundred patients worldwide, clinical trials have been limited to individual research centres assessing a few dozen patients. This has led to a confusing patchwork of studies that are virtually impossible to compare with one another. “It’s a dog’s breakfast,” says Freedman. “Different conditioning regimens, different choice of patients, different types of follow-up — it really doesn’t help us to have all these different approaches.”

Many leading MS researchers working with MSCs have joined forces to launch the International Mesenchymal Stem Cell Transplantation Study Group, devising a consensus roadmap on how future trials should be conducted5. The resulting guidelines will be implemented in a large-scale, multi-institutional, randomized controlled trial with patients in North America and Europe, which consortium members hope will begin in 2012. “Each individual group might be doing 15–30 patients, but if we have 20 groups doing that and we’re all using the same protocol and all analysing our data centrally, we’ll have something that’s not exactly equivalent but close to a multi-centre study,” says Freedman.

He points out that bone marrow-transplantation researchers have also begun to consolidate their efforts, and a similar ‘best practices’ document is on its way. Researchers in the United States, Canada and Europe are formulating plans for a large-scale, multi-centre trial. Burt has already embarked on a phase III randomized controlled trial of HSCT in partnership with researchers in Sweden and Brazil, and has recruited one-third of his 110 study subjects. “The neurologist doing the evaluation of disability has no idea of the treatment the patient has received, and our magnetic resonance imaging (MRI) data are being analysed at an MRI reading centre in Houston that is also blinded,” says Burt. “I’m very optimistic that a randomized trial will remove a lot of scepticism.”

Hope not hype
Despite the best efforts of researchers, stem cells are often portrayed as a miracle cure, and many MS patients who learn about stem-cell therapy from breathless newspaper articles or television features face let-downs. Even the clinicians had to learn some hard lessons in early studies. “In our HSCT clinical trial, we started with patients who had fairly advanced disease, wheelchair-bound or even bed-ridden,” says Richard Nash, a specialist in immunotherapy at the Colorado Blood Cancer Institute in Denver, Colorado “and we found that for many of these patients, even after transplantation they are going to continue to get worse.”

The outcomes of subsequent trials have been markedly improved by the recognition that patients with advanced MS might have crossed a threshold of nervous-system degeneration beyond which anything short of neuronal regrowth or replacement is likely to fail. This can be a difficult message for individuals with severe MS to hear. “The only time that patients get mad at me is when we don’t offer the transplant,” says Burt. “It’s hard to get patients to understand that this isn’t going to help them.”

In some cases, patients have pursued treatment at so-called ‘stem-cell clinics’ around the world, where they pay tens of thousands of dollars to be injected with cells of dubious provenance in an environment with minimal regulatory oversight. These clinics claim to treat any number of conditions with stem cells but offer little in the way of peer-reviewed efficacy data. At least one published report described a patient who developed tumours after a clinic transplanted fetal stem cells6, and in May 2011 Germany shut down the XCell Centre, where a young patient died from complications following autologous MSC transplantation. More recently, a case report from a team of neurologists in Arizona described how a teenage MS patient suffered a severe and debilitating inflammatory response during a course of stem-cell treatments at a clinic in Costa Rica7. The physicians were unable to determine the extent to which this strong immune response was attributable to the transplant, but they cite this example as justification for restricting experimental stem-cell treatments to clinical trial settings with proper oversight and safeguards. “We are really fighting those clinics,” says Martino, who has collaborated with colleagues in a survey of clinical stem-cell research in MS8. “We prepared this leaflet that anybody can easily download from various MS society websites, where we explained exactly what stage we’re at with the different types of stem cells.”

Most stem-cell researchers see cause for optimism but point out that good science and good medicine require considerable amounts of both time and effort. “The stem cell you use and how you use it will depend on the disease you’re treating as well as the stage, and it’s just beginning,” says Burt. “When I first started I thought I’d have all the answers in five years. But it doesn’t work that way — it takes time.”

References Author information Mancardi, G. & Saccardi, R. Lancet Neurol. 7, 626–636 (2008).
ISI PubMed Article Burt, R. K. et al. Lancet Neurol. 8, 244–253 (2009).
CAS ISI PubMed Article Bai, L. et al. Glia 57, 1192–636 (2009).
ISI PubMed Article Freedman, M. S. et al. Mult. Scler. 16, 503–636 (2010).
ISI PubMed Article Connick, P. et al. Lancet Neurol. 11, 150–636 (2012).
Amariglio, N. et al. PLoS Med. 6, e1000029 (2009).
CAS PubMed Article Alderazi, Y. J., Coons, S. W. & Chapman, K. J. Child Neurol. doi: 10.1177/0883073811422831 (7 December 2011).
Martino, G. et al. Nature Rev. Neurol. 6, 247–636 (2010).

Leukemia Sem Cells
In this issue of Blood, Gerber et al use aldehyde dehydrogenase (ALDH) activity to further subdivide the CD34+CD38− compartment in the bone marrow of acute myeloid leukemia (AML) patients. They identify a unique population with intermediate ALDH activity (ALDHint) that contains leukemia stem cells (LSCs). Moreover, persistence of this population after therapy is a marker of clinically significant minimal residual disease.1

Acceso directo a través del HINARI

Mark S Freedman, Antonio Uccelli
Mesenchymal stem cells are pluripotent cells that
can be derived and expanded from various tissues
from adults (eg, bone marrow or adipose tissue) or
fetuses (eg, placenta) and can differentiate into cells
of mesodermal origin (eg, bone, cartilage, or fat).
These stem cells possess unique immunomodulatory
properties and can control drug-resistant graftversus-
host disease in people; in animals, they
also seem to limit damage to, or mediate repair
of, CNS tissue via mechanisms other than cell
replacement or transdiff erentiation, probably via
their paracrine function.1 The potential to repair the
CNS or protect it from further damage is precisely
what is being sought as a treatment for progressive
forms of multiple sclerosis (MS). In this issue of
The Lancet Neurology, Peter Connick and colleagues2
assess the effects of a single intravenous dose of
autologous mesenchymal stem cells in the CNS of ten
patients with secondary progressive MS—a disorder
for which there is no proven therapy, despite many
successful agents being used to treat its predecessor,
relapsing-remitting MS.
How to measure repair in MS accurately in the
absence of pathological confi rmation3 has not
been established. Patients who improve after the
overt infl ammatory phase of a relapse and in whom
new lesion formation has stopped might simply
be recovering from these acute events rather than
undergoing active repair. It is also diffi cult to establish
whether lesions on MRI scans are truly improving or
shrinking because of repair or whether they are showing
resolution of infl ammation and oedema. Nevertheless,
evidence of repair with some newer techniques, such
as a change in lesional magnetisation transfer ratio on
MRI, does correlate with histological fi ndings.4 Rather
than looking for signs only of general repair, Connick
and colleagues concentrated on the visual pathway, a
system that can be assessed for structure and function
with validated imaging and neurophysiological
techniques. The investigators chose patients who had
a clear history and objective evidence of optic nerve
involvement due to demyelination, which they refer
to as the sentinel lesion. More importantly, the optic
nerve event was reasonably remote (at least 2 years
from the treatment), such that any acute repair from
the event would have been completed. To ensure
stability, Connick and colleagues assessed patients
several times before treatment, and although two
patients had what might have been an attack of MS,
neither had symptoms or signs involving the anterior
visual pathways.
So far, we have not really been convinced that
any treatment for MS is associated with repair.
Connick and colleagues might be showing the
early signs of this process, somehow mediated by
a single injection of mesenchymal stem cells. They
showed that over the course of 6–10 months after
a single infusion there was recovery of vision that
seemed functional (visual acuity and low contrast
sensitivity), neurophysiological (reduction of the
visual evoked response latency and improved visual
evoked response amplitudes), and structural (increase
in the optic nerve cross-sectional area). What can be
measured in the anterior visual pathway might be an
indicator of a more general process within the CNS,
which is suggested by the reduction in functional
disability (the expanded disability status score) as well
as large, but statistically non-significant, changes in
T1 lesion volume and magnetisation transfer ratio.
However, many measures did not show statistically
significant changes after treatment; particularly
disappointing were the results for optical coherence
tomography, which we all hoped might be a sensitive
index for repair. Nevertheless, this did not detract
from the important findings consistent with CNS
recovery, particularly in the anterior visual system.
Furthermore, there were no serious adverse events in
any patients.
This study is not defi nitive, and Connick and
colleagues have carefully pointed out some of the
caveats of a small non-randomised single-centre
study, such as pretest versus post-test design with no
control group to confi rm that changes after treatment
were directly attributable to treatment rather than
natural history. However, the signs of repair measured
in most of the patients with secondary progressive MS
less than a year after a single infusion of mesenchymal
stem cells raise substantial interest. The hope and
faith of stem-cell research has been to be able to
repair a failing nervous system—with a particular
focus on the use of mesenchymal stem cells.5 Most
investigators agree that these cells have the potential
to repair, but many thought they should fi rst seek to
prove the biological eff ect of modulating immune
responses to reduce infl ammation and explore for
repair signals before leaping into a clinical trial aimed
directly at showing repair.6 Connick and colleagues
have shown us that sometimes it might be better to
leap before looking.
Mark S Freedman, Antonio Uccelli
University of Ottawa Neurology Program, Ottawa, ON, Canada
(MSF); and Department of Neurosciences, Ophthalmology and
Genetics, University of Genoa, Italy (AU)
Articulo a trevés del HINARI

Miles de turistas acuden a China para someterse a tratamientos con células madre que no están autorizados y que pueden poner en riesgo su salud, revela en su último número la revista científica británica “Nature”.

Según esta publicación, un centenar de clínicas chinas tienen páginas web en las que ofertan tratamientos con células madre contra enfermedades como el párkinson, la esclerosis múltiple, el alzhéimer y la diabetes.

Algunos de estos centros forman parte de grandes complejos hospitalarios, lo que les aporta una imagen de seriedad y aceptación, y todos subrayan el éxito de sus terapias pese a que ninguno ha publicado nunca los resultados de sus ensayos clínicos, afirma el autor del estudio, David Cyranoski.

En su opinión, atraen a miles de extranjeros que viajan a China con el reclamo del turismo médico, seducidos por supuestos casos de éxito que no se han demostrado.

De media, uno de estos tratamientos puede requerir entre cuatro y ocho inyecciones de células madre, que proceden del cordón umbilical, tejido adiposo o fetos de abortos, y cuyo precio asciende en cada caso a varios miles de euros.

Sin embargo, varios científicos de distintos países consultados por “Nature” insisten en que estas terapias aún no están listas para el público general y que algunas de ellas pueden provocar complicaciones graves como enfermedades autoinmunes e incluso cáncer en el caso del tratamiento del autismo.

“No está claro que la inyección de células madre sobreviva más de unos días en el organismo de los pacientes”, apunta por ejemplo Oliver Cooper, experto en células madre y párkinson del hospital McLean de Belmont (EEUU).

En mayo de 2009, el Ministerio de Sanidad de China clasificó los tratamientos con células madre como “tecnologías médicas de alto riesgo”, que requieren la aprobación de una comisión técnica para que una clínica pueda ofertarlas.

Aunque a día de hoy no se ha concedido aún ninguna licencia de este tipo, el artículo de “Nature” denuncia que sólo en 2009 ya existían en China un centenar de empresas con estos tratamientos.

“Pese a las reformas y los esfuerzos del Ministerio de Sanidad, aparentemente esta industria sigue creciendo”, afirma Doug Sipp, experto en legislación y ética sobre células madre del Centro RIKEN de Biología del Desarrollo de Kobe (Japón), citado en el artículo.

En un nuevo intento de poner fin a esta actividad, el Ministerio de Sanidad chino decretó en enero nuevas medidas que obligan a las clínicas a inscribir en un registro sus investigaciones y actividades, la fuente de sus células madre y sus líneas éticas.

El ministerio anunció asimismo una moratoria nacional para los nuevos ensayos clínicos con células madre y agregó que los pacientes en los ensayos clínicos en curso no deberían pagar por ellos.

Sin embargo, según explicó un portavoz del Ministerio de Sanidad a la revista británica, ninguna clínica ha cumplido aún con el proceso de registro y la mayoría continúa ofreciendo las mismas terapias con las células madre.

En: Noticias #

Una de las aplicaciones pioneras en reconstrucción mamaria postmastectomía es el trasplante de tejido adiposo, es decir, la inyección de grasa de la propia paciente.

Los objetivos de la medicina regenerativa se basan en proporcionar los elementos necesarios para la reparación in vivo, estimulando al propio organismo a autorepararse, por medio del uso las células madre, la ingeniería tisular o la terapia génica. Esta disciplina da un paso más con respecto a los tratamientos tradicionales en trasplantes o en terapias con órganos artificiales.

“El sector de la cirugía plástica será uno de los que más se podrá beneficiar de los avances de la medicina regenerativa”, ha explicado la Dra. Gemma Pons, cirujana miembro de la SECPRE, en el marco de su XLVII Congreso Nacional.

Según esta especialista, “aunque la medicina regenerativa se encuentra, básicamente, a nivel de investigación científica, su aplicación en el campo de la medicina en general, y de la cirugía plástica en particular, tiene un gran potencial”. Concretamente, una de las dos grandes líneas de investigación en las que se divide esta disciplina se centra en la cicatrización de heridas, utilización de factores plaquetarios para disminuir la inflamación y el fortalecimiento del sistema inmunológico para reducir el rechazo de órganos en trasplantes.

En reconstrucción mamaria post-mastectomía, el trasplante de tejido adiposo, es decir la inyección de grasa de la propia paciente, que contiene células madre pluripotenciales, es una de las aplicaciones pioneras de la medicina regenerativa en cirugía plástica, y con la que se están consiguiendo resultados prometedores. “Esta técnica consigue restaurar la mama en casos de resecciones parciales y refinar reconstrucciones mamarias llevadas a cabo con otras técnicas (implantes, colgajos, etc.)”, asegura la Dra. Pons.

El trasplante de tejido adiposo también es utilizado para los casos de aumento mamario en el campo de la cirugía estética, con buenos resultados. Asimismo, otra de las aplicaciones de la medicina regenerativa es la utilización de matrices tisulares, las cuales actúan como andamios que redirigen al propio organismo para crear nuevos tejidos.

Por otro lado, “en algunas cirugías faciales como el lifting o la rinoplastia, gracias al uso de plasma enriquecido en plaquetas y líquidos enriquecidos con factores de crecimiento, se están consiguiendo efectos muy satisfactorios al disminuir la inflamación y facilitar la posterior reparación y cicatrización tisular”, concluye esta especialista.
abril 16/2012 (JANO. es)

En: Noticias #

En un artículo que se publica en Current Protocols in Cytometry, Jordi Petriz, investigador principal del laboratorio de células madre y cáncer del Instituto de Investigación Valle de Hebrón, habla de las células madre de la “side population” por citometría de flujo y recuerda que es uno de los más consultados de la publicación, a pesar de que han transcurrido varios años desde que apareció originalmente.

Entre la redacción del primer y el segundo artículo, los cambios en este ámbito han sido muy numerosos. Uno de los aspectos más relevantes es la descripción de los transportadores multidroga como posibles reguladores de la transducción de la señal tanto en células madre como en células madre tumorales, además de producir resistencia a la quimioterapia.

La dificultad en identificar estas células y poder estudiarlas está impidiendo que se conozca cuál es su función fisiológica en humanos.

“Por este motivo, nos estamos planteando estudiar el papel de los transportadores multidroga en la regulación de la transducción de la señal en las células madre y analizar su función protectora en las vías de señalización que son fundamentales para el mantenimiento de este fenotipo de célula madre”, ha explicado Petriz, que preside la Sociedad Ibérica de Citometría y coordina su grupo de trabajo sobre células madre.

Las células madre de la side population son un tipo muy minoritario que se encuentra en todos los tejidos estudiados hasta la fecha en humanos, en una proporción muy pequeña. Como ha recordado Petriz, la dificultad en identificar estas células y poder estudiarlas a nivel básico está impidiendo que se conozca cuál es su función fisiológica en humanos.

“Parece que está muy relacionada con la renovación de los tejidos y el mantenimiento de la homeostasis tisular durante toda la vida. Por experimentos en ratones se sabe que estas células tienen una gran plasticidad y, por ejemplo, las que se encuentran en la médula ósea no solo generan sangre, sino que pueden generar cualquier otro tipo de tejido. Y, de la misma manera, las que se encuentran en el cerebro no solo tienen capacidad de regenerar el cerebro sino que, debido a esta gran plasticidad, tienen capacidad de formar sangre, músculo u otro tipo de tejido”.

Primeros pasos
Por eso, se pensó que estas células podrían tener un gran potencial terapéutico en humanos, ya que podrían utilizarse de manera autóloga en medicina regenerativa expandiéndolas primero y diferenciándolas después al tejido de interés. Pero “en humanos es aún un campo muy desconocido, aunque se han hecho muchas aproximaciones en ratón. Las células madre de la side population se encuentran en tumores y en leucemias, por lo que pueden tener una importancia como células madre propias tanto del tumor como de la leucemia; por lo que esta sería la verdadera diana terapéutica que interesaría eliminar a través de la terapia en cáncer”.

Los avances en la citometría de flujo han propiciado la comprensión de todos los mecanismos. “Este es un aspecto fundamental porque, en la actualidad, no tenemos ningún marcador fenotípico que nos permita identificar estas células tan minoritarias: solo puede realizarse por la función derivada de la expresión de estos transportadores multidroga tanto en las células madre como en las células madre tumorales de la side population. Y la citometría de flujo es la única herramienta que permite identificarlas y aislarlas vivas para expandirlas o hacer estudios posteriores de biología molecular y tratar de comprender mucho mejor su compleja biología”, ha destacado Petriz.
abril 15/2012 (Diario Médico)

En: Noticias #