ArticleYong Zhao1*, Zhaoshun Jiang2, Tingbao Zhao3, Mingliang Ye4, Chengjin Hu5,
Zhaohui Yin2, Heng Li6, Ye Zhang7, Yalin Diao4, Yunxiang Li4, Yingjian Chen5,
Xiaoming Sun5, Mary Beth Fisk8, Randal Skidgel9, Mark Holterman10, Bellur
Prabhakar11, Theodore Mazzone1
Abstract
Background
Inability to control autoimmunity is the primary barrier to developing a cure for
type 1 diabetes (T1D). Evidence that human cord blood-derived multipotent stem
cells (CB-SCs) can control autoimmune responses by altering regulatory T cells
(Tregs) and human islet β cell-specific T cell clones offers promise for a new
approach to overcome the autoimmunity underlying T1D.
Methods
We developed a procedure for Stem Cell Educator therapy in which a patient’s
blood is circulated through a closed-loop system that separates lymphocytes
from the whole blood and briefly co-cultures them with adherent CB-SCs before
returning them to the patient’s circulation. In an open-label, phase1/phase 2
study, patients (n = 15) with T1D received one treatment with the Stem Cell
Educator. Median age was 29 years (range: 15 to 41), and median diabetic
history was 8 years (range: 1 to 21).
Results
Stem Cell Educator therapy was well tolerated in all participants with minimal
pain from two venipunctures and no adverse events. Stem Cell Educator therapy
can markedly improve C-peptide levels, reduce the median glycated hemoglobin
A1C (HbA1C) values, and decrease the median daily dose of insulin in patients
with some residual β cell function (n = 6) and patients with no residual pancreatic
islet β cell function (n = 6). Treatment also produced an increase in basal and
glucose-stimulated C-peptide levels through 40 weeks. However, participants in the Control Group (n = 3) did not exhibit significant change at any follow-up.
Individuals who received Stem Cell Educator therapy exhibited increased
expression of co-stimulating molecules (specifically, CD28 and ICOS), increases
in the number of CD4+CD25+Foxp3+ Tregs, and restoration of Th1/Th2/Th3
cytokine balance.
Conclusions
Stem Cell Educator therapy is safe, and in individuals with moderate or severe
T1D, a single treatment produces lasting improvement in metabolic control. Initial
results indicate Stem Cell Educator therapy reverses autoimmunity and promotes
regeneration of islet β cells. Successful immune modulation by CB-SCs and the
resulting clinical improvement in patient status may have important implications
for other autoimmune and inflammation-related diseases without the safety and
ethical concerns associated with conventional stem cell-based approaches.
Trial registration: ClinicalTrials.gov number, NCT01350219
Bone marrow mononuclear cells and acute myocardial infarction.Stem Cell Research & Therapy 2012, 3:2
Review
Bone marrow mononuclear cells and acute myocardial infarction
Samer Arnous1, Abdul Mozid1, John Martin1 and Anthony Mathur2*
* Corresponding author: Anthony Mathur a.mathur@qmul.ac.uk
Author Affiliations
1 Department of Cardiology, London Chest Hospital, Bonner Road, London E2 9JX, UK
2 Department of Cardiology, London Chest Hospital, Queen Mary University of London, Barts and the London NHS Trust, Bonner Road, London E2 9JX, UK
For all author emails, please log on.
Stem Cell Research & Therapy 2012, 3:2 doi:10.1186/scrt93
The electronic version of this article is the complete one and can be found online at: http://stemcellres.com/content/3/1/2
Published: 17 January 2012
© 2012 BioMed Central Ltd
Abstract
Stem cell transplantation is emerging as a potential therapy to treat heart diseases. Promising results from early animal studies led to an explosion of small, non-controlled clinical trials that created even further excitement by showing that stem cell transplantation improved left ventricular systolic function and enhanced remodelling. However, the specific mechanisms by which these cells improve heart function remain largely unknown. A large variety of cell types have been considered to possess the regenerative ability needed to repair the damaged heart. One of the most studied cell types is the bone marrow-derived mononuclear cells and these form the focus of this review. This review article aims to provide an overview of their use in the setting of acute myocardial infarction, the challenges it faces and the future of stem cell therapy in heart disease.
Introduction
Despite the recent advances in percutaneous intervention, drug and device therapy, patients with acute myocardial infarction (AMI) and resulting left ventricular impairment have 13% mortality at 1 year [1]. Following the loss of over one billion cardiomyocytes in a functionally significant MI, the overloaded surviving cardiomyocytes undergo abnormal remodelling, eventually leading to heart failure. This condition, a leading cause of death and disability in the developed world, is associated with 5-year mortality rates of up to 70% in symptomatic patients [2]. Current conventional therapies do not correct underlying defects in cardiac muscle cell number [3].
The only therapeutic option that currently addresses cardiomyocyte loss is heart transplantation. However, due to stringent selection criteria and chronic shortage of donor hearts, the vast majority of patients are deemed unsuitable or never receive a transplant. Therefore, preventing this progression post-MI is a major challenge requiring novel therapeutic strategies such as stem cell transplantation to improve the prognosis and quality of life for these patients.
The traditional view that the heart is a terminally differentiated organ has been challenged by the discovery of differentiation of stem cells into cardiomyocytes in animal and human hearts [4-7]. This in turn has led to the exciting possibility for regenerative therapy for cardiomyocyte loss after a MI. The demonstration of functional recovery of myocardium through cardiomyogenesis and neoangiogenesis in AMI in murine models by Orlic and colleagues [8] generated tremendous interest in the potential of bone marrow-derived stem cells. Since then, the cardiomyogenic ability of these cells has been challenged. However, studies continue to demonstrate improvement in cardiac function and reduction in infarct size. It should be noted that progenitor cells also contribute to cardiac repair by mechanisms beyond the growth of new cardiomyocytes and as such may offer an ‘indirect’ benefit.
Animal and human trials
The most promising and obvious cell type for the growth of new cardiomyocytes is the embryonic stem cell; however, considerable technical and ethical issues exist with these cells, which must be overcome before their successful use in humans. Adult stem cells are an attractive option to explore for transplantation as they are autologous, but their differentiation potential is more restricted than embryonic stem cells. Currently, the major sources of adult cells used for basic research and in clinical trials originate from the bone marrow. The bone marrow mononuclear subset is heterogeneous and comprises mesenchymal stem cells, haematopoietic progenitor cells and endothelial progenitor cells. The differentiation capacity of different populations of bone marrow-derived stem cells into cardiomyocytes has been studied intensively. The results are rather confusing and difficult to compare, since different isolation and identification methods have been used to determine the cell population studied. To date, only mesenchymal stem cells seem to form cardiomyocytes, and only a small percentage of this population will do so in vitro or in vivo. Pragmatically, the translation of the basic science into clinical research has followed a common pathway: injection of bone marrow-derived mononuclear cells (BMMNCs) as a source of stem cells into the heart. Table 1 provides a summary of clinical trials using BMMNCs in patients with acute MI.
Table 1. Clinical trials using autologous bone marrow mononuclear cells in patients with acute myocardial infarction
Trials with no sham bone marrow harvest or intracoronary re-infusion in the control group
In the first human trial, Strauer and colleagues [9] re-infused intracoronary BMMNCs 7 days after myocardial infarction (MI). The mean number of mononuclear cells was 2.8 × 107. There was a significant improvement in myocardial perfusion and a reduction in the infarct region in the cell therapy group. The Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI) investigators randomised patients into intracoronary infusion of BMMNCs or ex vivo expanded circulating progenitor cells 4 days after MI [10]. There was a significant improvement in global and regional left ventricular (LV) function in both groups and a beneficial effect on the post-infarction remodelling process manifest by a profound improvement in wall motion abnormalities in the infarct area and a significant reduction in end-systolic LV volume at 4 months post-MI. The LV ejection fraction (LVEF) further improved at 12 months, resulting in a total increase of 9.3% at 1 year [11]. Of interest, there was no difference between the two active treatment groups. The mean number of infused cells was 245 × 106, which contained haematopoietic progenitor, mesenchymal and stromal cells. However, a major limitation of both of these trials was the lack of a control group receiving sham bone marrow harvest or intracoronary re-infusion.
Another trial in which there was no sham procedure is the Autologous Stem-Cell Transplantation in Acute Myocardial Infarction (ASTAMI) trial, which included only patients with acute anterior MI. The intracoronary re-infusion of BMMNCs 4 to 8 days after infarction did not have a beneficial effect on LVEF compared to percutaneous coronary intervention (PCI) alone at 6 months [12]. This lack of beneficial effect may be explained by the different cell processing protocols used in this trial. Cell processing protocols may have a significant impact on the functional capacity of bone marrow-derived stem cells [13]. Comparison of different isolation protocols revealed a vastly reduced recovery of mononuclear cells and nullification of the neovascularisation capacity when the ASTAMI cell isolation and storage protocol was used [13].
The Bone Marrow Transfer to Enhance ST-Elevation Infarct Regeneration (BOOST) trial, a slightly larger trial, included 60 patients that were randomised to receive intracoronary BMMNCs or standard therapy 4.8 days after successful PCI following AMI. There was a significant improvement in global LVEF in the cell treatment group at 6 months without an effect on LV remodelling [14]. However, this improvement was not maintained at 18 months. The mean number of bone marrow cells that were infused contained 9.5 × 106 CD34+ and 3.6 × 106 haematopoietic colony-forming cells. The improvement in LVEF did not correlate with the number of CD34+ cells or haematopoietic colony forming cells. Again, a major limitation of the BOOST trial is that the control group did not undergo a sham bone marrow harvest or intracoronary infusion.
The first long-term study involving 62 patients who underwent intracoronary BMMNC transplantation 7 days post-AMI not only resulted in an early significant improvement in ejection fraction (EF) and infarct size, but there was also a significant reduction in mortality and improvement in exercise capacity compared to controls at 5 years [15].
Randomised controlled trials
The Transcatheter Transplantation of Stem Cells for Treatment of Acute Myocardial Infarction (TCT-STAMI) trial, which included a control group receiving a placebo infusion, showed a significant (approximately 5%) improvement in LVEF of patients receiving intracoronary BMMNCs at 6 months [16].
Intracoronary bone marrow derived progenitor cells in acute infarction (REPAIR-AMI), a large randomized double-blind controlled trial that included over 200 patients, showed an improvement in the primary endpoint in the treatment group that was an absolute change in global LVEF from baseline to 4 months, as measured by quantitative left ventricular angiography [17]. Furthermore, the pre-specified cumulative endpoint of death, MI, or revascularisation was significantly reduced, and this benefit was maintained at one year follow-up [18]. The mean increase in LVEF in the BMMNC group was 2.5% and there was an inverse relationship between the baseline EF and the degree of improvement. For example, patients with a baseline EF below the median value (48.9%) had an absolute increase in global EF that was three times higher than that in the placebo group. In contrast, the improvement in LVEF in patients with a baseline EF that was above the median value was non-significant (0.3%). The timing of cell infusion post-PCI also had an effect on the primary endpoint. Patients in whom the cells were infused ≥5 days post-PCI were the only ones who derived benefit.
By contrast, the LEUVEN-AMI study by Janssens and colleagues [19] showed that intracoronary re-infusion of BMMNCs within 24 hours of reperfusion was associated with a greater reduction in infarct size and improved regional systolic function, but no overall improvement in global left ventricular function compared to controls.
Trials that used two different cell populations
More recently, the Myocardial Regeneration by Intracoronary Infusion of Selected Population of Stem Cells in Acute Myocardial Infarction (REGENT) trial, which included patients with anterior MI, uniquely compared two cell types. Patients were randomized to receive intracoronary infusion of unselected (n = 80) or selected CD34+CXCR4+ (n = 80) BMMNCs, or to the control group (n = 40) [20]. Although patients in the treatment group had a 3% improvement in LVEF, this did not reach statistical significance. However, the primary endpoint analysis included 5 hours) may be more likely to have significant improvement of LVEF following the BMMNC infusion [20].
The timing of cell infusion may also play a role on the derived benefit. Although the REPAIR-AMI trial suggests that the enhanced improvement of the LVEF was confined to patients who were treated ≥5 days after primary PCI, the investigators of the HEBE and REGENT trials showed no interaction between the timing of cell infusion and derived benefit. The meta-analysis by Martin-Rendon and colleagues [22], however, showed that the benefit of stem cell therapy was even greater when the BMMNCs were infused >7 days after MI. The effect of timing on the beneficial effects of BMMNC administration is further supported by the study by Lai and colleagues [31] that showed that intracoronary BMMNC administration provided cardio-protection in a fashion similar to ishaemic preconditioning. This benefit was only seen when the myocardium had not been preconditioned by other means. An ongoing study at our centre, the REGENERATE-AMI (ClinicalTrial.gov NCT00765453), is designed to study the delivery of BMMNCs at very early time points (within 6 hours of PCI). The purpose of this design is to replicate the animal models where very early interventions lead to a significant (40%) improvement in cardiac function [8].
The dose of infused BMMNCs has varied between different trials with variable results. There appears to be a dose-dependent improvement in EF, with the benefit of BMMNCs only seen when doses higher than 108 are administered [22].
Direct (transdifferentiation) and indirect (paracrine and angiogenesis) effects of stem cells
To date, there is no direct clinical evidence that cellular cardiomyogenesis in fact occurs in the human heart after transplantation of progenitor cells, and over the past few years, various experiments using different types of stem cells have shown that 4 days after reperfusion (based on available evidence). Furthermore, given the seemingly small improvements that these trials have shown, the cost-effectiveness of cell therapy will also need to be addressed.
Two ongoing randomised controlled trials (TIME and late TIME studies) may help us understand whether the timing of cell administration plays an important role. The TIME study (Clinicaltrials.gov NCT00684021) is a trial designed to assess the effect of timing (3 versus 7 days) of BMMNC administration versus placebo in patients with acute MI. The LATE TIME study (Clinicaltrials.gov NCT00684060) will assess the effect of BMMNC administration 2 to 3 weeks after a MI.
Future cells
Animal and human studies have clearly shown that stem cell engraftment into the myocardium is associated with improvement in cardiac function; however, the quest for the optimal population of cells remains a challenge [85,86]. Embryonic stem cells are able to transform into cardiomyocytes and can replicate indefinitely, although ethical issues – their potential to form teratomas and the need for immunosuppressive therapy – have hindered their use in clinical trials. Furthermore, one of the major limitations of adult stem cells, including skeletal myoblasts and bone marrow-derived stem cells, is their limited ability to cross their lineage boundaries.
Fat tissue-derived multipotent stem cells [87], multi-potential cells from bone marrow or skeletal muscle [88,89], somatic stem cells from placental cord blood [90], and cardiac-resident progenitor cells [32,91] all show promising pre-clinical and some clinical applications.
Ultimately, cells that more closely resemble embryonic stem cells in their regenerative potential without the ethical issues provide an important future direction. A cell type that comes close, and is on the horizon of being tested for potential clinical application, is the inducible pluripotent stem cell (iPSC). iPSCs can be generated from adult human somatic cells by retroviral transduction [92], have similar differentiation potential and may provide an alternative to pluripotent embryonic stem cells.
The future of bone marrow stem cells
For the time being, it is important to establish whether the simple unfractionated bone marrow cell approach has clinical benefit, given the large number of studies that have been performed using this cell type without providing a clear answer. Meta-analysis suggests a positive effect on surrogate cardiac end-points in studies using BMMNCs to treat AMI. There is now a need to perform a large scale clinical trial using clinical hard end-points such as mortality to establish whether the positive effects seen on surrogate end-points can indeed translate to meaningful clinical benefits.
Abbreviations
AMI: acute myocardial infarction; ASTAMI: Autologous Stem-Cell Transplantation in Acute Myocardial Infarction; BMMNC: bone marrow-derived mononuclear cell; BOOST: Bone Marrow Transfer to Enhance ST-Elevation Infarct Regeneration; EF: ejection fraction; LV: left ventricular; LVEF: left ventricular ejection fraction; MI: myocardial infarction; PCI: percutaneous coronary intervention; REPAIR-AMI: Intracoronary bone marrow derived progenitor cells in acute infarction; SDF: stromal-cell-derived factor.
Competing interests
The authors have no relevant affiliations or financial involvement with any organisation or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.
Acknowledgements
This work forms part of the research themes contributing to the translational research portfolio of Barts and the London Cardiovascular Biomedical Research Unit, which is supported and funded by the National Institute of Health Research.
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Un estudio del RECAVA muestra que los pacientes con daños en una sola arteria tienen el triple de células madre en sangre que los pacientes con dos o tres arterias afectadas.
Investigadores de la Red de Investigación Cardiovascular (RECAVA), perteneciente al Instituto de Salud Carlos III, han logrado medir por primera vez la relación entre el área cardíaca dañada por un infarto y la cantidad de células madre que circulan por la sangre para reparar la zona lesionada.
El estudio, publicado en la Revista Española de Cardiología, ha mostrado que los pacientes que presentaban daños en una sola arteria tenían el triple de células madre en sangre que los pacientes con dos o tres arterias afectadas.
“La lógica invitar a pensar que cuanto mayor es el número de arterias lesionadas, mayor será la cantidad de células madre en sangre destinadas a reparar el corazón; sin embargo, esta investigación demuestra que no es así”, explica el coordinador del trabajo, Manuel Jiménez Navarro, del Área del Corazón del Hospital Clínico Universitario Virgen de la Victoria de Málaga.
La cuantificación ha podido realizarse gracias a una técnica llamada citometría de flujo, que permite cuantificar la cantidad de anticuerpos que rodean a las células madre en la sangre. Los investigadores de RECAVA también cuantificaron los mediadores, es decir, las moléculas que se liberan cuando una zona del corazón sufre un infarto, y que reciben el nombre de citoquinas.
Dichas citoquinas actúan como señales que avisan a diferentes zonas del cuerpo, entre ellas la medula ósea, para que generen las células madre que deben ir a reparar la zona infartada.
El estudio muestra cómo los pacientes que han sufrido un infarto tienen más células madre circulantes en sangre que los pacientes libres de enfermedad, en una proporción de 14 a 1.
También la cantidad de mediadores que influyen en el proceso de liberación de células madres es mayor en los pacientes infartados respecto a los sanos, siendo en este caso la proporción de 8 a 1. En ambos casos las extracciones de sangre se realizaron en distintas fases tras el infarto con el objetivo de estudiar la cinética de liberación de estas células.
Revista Española de Cardiología
En: Noticias 
Un estudio abierto en fase 2a, que administró células madre mesenquimales autólogas a pacientes con esclerosis múltiple secundaria progresiva, ha evidenciado mejoras estructurales, funcionales y fisiológicas en algunos criterios de valoración visual, después del tratamiento, lo que es sugestivo de neuroprotección.
El estudio tuvo como objetivo evaluar la seguridad y la eficacia de estas células como tratamiento potencial neuroprotector para la esclerosis múltiple secundaria progresiva. Los diez pacientes seleccionados padecían una afectación de las vías visuales (EDSS: 5,5-6,5).
La dosis media administrada fue de 1,6 × 106 células por kg de peso (rango: 1,1-2,0 × 106). Tras el tratamiento se evidenció mejoría en la agudeza visual y en la latencia de respuesta evocada visual, junto con un aumento en el área del nervio óptico. No se comunicó ningún efecto adverso grave.
Febrero 15/2012 (Neurologia.com)
Nota: Los lectores del dominio *sld.cu acceden al texto completo a través de Hinari.
Connick P, Kolappan M, Crawley C, Webber DJ, Patani R, Michell AW, et al.Autologous mesenchymal stem cells for the treatment of secondary progressive multiple sclerosis: an open-label phase 2a proof-of-concept study.The Lancet Neurology (doi:10.1016/S1474-4422(11)70305-2), Volume 11, Issue 2, Pages 150 – 156, Feb 2012
En: Noticias
La administración intraarterial de células madre permite una mejora clínica de los pacientes diabéticos con isquemia crítica de la extremidad inferior y fomenta la formación de nuevos vasos sanguíneos, según un ensayo clínico que se ha presentado en el II Congreso de la Sociedad Española de Heridas, que se celebró en Madrid.
Uno de los autores del estudio, Rafael Ruiz-Salmerón, responsable de la Unidad Clínica Endovascular del Hospital Virgen Macarena, de Sevilla, ha explicado que este ensayo clínico multidisciplinar se inició en 2008 y sus resultados se publicaron el año pasado en Cell Transplantation (doi.org/10.3727/096368910X0177).
Se trata de un registro prospectivo en fase I-II que se puso en marcha con dos objetivos. El primero y más importante de ellos fue “analizar angiográficamente si se crean nuevos vasos sanguíneos. Pensábamos que sí, pero hasta ahora no se había documentado”, ha señalado el cirujano vascular.
En segundo término se pretendía averiguar la eficacia de un nuevo modelo de aplicación, la administración intraarterial. El experto ha precisado que también se analizaron otros aspectos relevantes en pacientes con este tipo de isquemia, como la seguridad, el índice tobillo-brazo o la cicatrización de las úlceras.
En el ensayo participaron 20 pacientes diabéticos tipo 2 con isquemia crítica de la extremidad inferior y sin posibilidad de revascularización. El miembro diana para la aplicación de la nueva terapia fue aquel que tenía un peor estado clínico.
En cuanto a la preparación de las células, Ruiz-Salmerón ha indicado que en este ensayo “no fueron consideradas como medicamentos; para ello hubo que cumplir el requisito de que todo el proceso se llevase a cabo en el quirófano”.
Cuando cada paciente entraba en el quirófano, los hematólogos le realizaban una punción de médula ósea con la que extraían entre 60 y 100 mililitros de contenido. Para el procesamiento fue necesario instalar en el quirófano distintos dispositivos, como una cámara de flujo laminar y una centrifugadora. De esta manera se obtenía una pequeña banda de células mononucleadas que se separaban hasta obtener 20 mililitros de suero.
A continuación, los cirujanos vasculares accedían al paciente por vía radial. Mediante catéteres llegaban al miembro diana y depositaban las células en la región más distal permeable. Para evitar que las células acabasen en el torrente sanguíneo, ocluían la arteria durante tres minutos y las administraban lentamente. “Inyectamos una media de 200 millones de células mononucleadas por paciente”, ha declarado el experto. Los pacientes eran dados de alta en el mismo día.
Al cabo de tres meses se realizó la primera evaluación, en la que los especialistas sometieron a los pacientes a angiografía y utilizaron el programa llamado MetaMorph para analizar los vasos. Ruiz-Salmerón ha explicado que, de los 19 individuos a los que se les pudo realizar seguimiento angiográfico, “en 13 se observó una mejora clara de la extensión y la densidad vascular”. Además, se apreció una correlación de estos resultados con la mejoría clínica de los afectados. El índice tobillo-brazo mejoró sustancialmente, y lo mismo puede decirse de los resultados según la clasificación Rutherford-Becker y la Escala de la Universidad de Texas.
También se observó algo que Ruiz-Salmerón ha calificado como “hallazgos sorprendentes”. En tres pacientes se produjo una “sobreexpresión de la neovascularización arteriovenosa”, aunque el especialista ha apuntado que este hecho “no tuvo traducción clínica”.
“Pensamos que es una terapia eficaz, cómoda para el paciente y con efectos rápidos. En el primer mes ya se aprecian cambios, y a los tres meses todavía más”, ha concluido el cirujano vascular. El porcentaje de respuesta fue del 70 %.
Durante el periodo de estudio no hubo problemas de seguridad ni amputaciones mayores, si bien se produjeron cuatro muertes. El especialista ha aclarado que estos fallecimientos se debieron a problemas cardiovasculares y, por lo tanto, son achacables a la evolución normal de los pacientes participantes.
El grupo de investigación ha iniciado otro ensayo similar que empleará células madre mesenquimales en vez de las de médula ósea.
Febrero 09/2012 (Diario Médico)
Nota: Los lectores del dominio *sld.cu acceden al texto completo a través de Hinari.
Ruiz-Salmeron R, de la Cuesta-Diaz A, Constantino-Bermejo M, Pérez-Camacho I, Marcos-Sánchez F, Hmadcha A, Soria B.Angiographic Demonstration of Neoangiogenesis After Intra-arterial Infusion of Autologous Bone Marrow Mononuclear Cells in Diabetic Patients With Critical Limb Ischemia.Cell Transplant. 2011;20(10):1629-39.
http://www.sld.cu/servicios/aldia/view-aldia.php?idn=20551
En: Noticias
ISSN: 1561-3194
Rev. de Ciencias Médicas. diciembre 2011; 15(4)
HOSPITAL GENERAL DOCENTE ABEL SANTAMARÍA CUADRADO PINAR DEL RÍO
Autotrasplante de células madre adultas en defecto óseo de rama mandibular por quiste dentígero
Autotransplantation of adult stem cells in an osseous defect of the mandibular branch per dentigerous cyst
Luís E. Torres Rodríguez1, Maria E. Marimón Torres2, Felicia C. Morejón Álvarez3, René Camacho Díaz4, Liseet Leon Amado5
1Especialista de Primer Grado en Cirugía Maxilofacial. Instructor. Máster en Urgencias Estomatológicas. Hospital General Docente “Abel Santamaría Cuadrado”. Pinar del Río. Correo electrónico:coco@has.sld.cu
2Especialistas de Segundo Grado en Cirugía Maxilofacial. Hospital General Docente “Abel Santamaría
Cuadrado”. Pinar del Río.
3Especialista de Segundo Grado en Cirugía Maxilofacial. Hospital General Docente “Abel Santamaría Cuadrado”.
Pinar del Río.
4Especialista de Primer Grado en Cirugía Maxilofacial. Hospital General Docente “Abel Santamaría Cuadrado”.
Pinar del Río.
5Licenciada en Medicina Transfusional. Hospital General Docente “Abel Santamaría Cuadrado”. Pinar del Río.
RESUMEN
Propósitos del estudio: indagar en la formación ósea de cavidades quísticas de los maxilares a partir de
células madres adultas.
Método: se realiza la presentación de un paciente que presentaba un quiste dentígero en rama mandibular izquierda y que había provocado gran destrucción ósea, lo cual se comprobó al examen físico y estudios complementarios, tomografía axial compuarizada (TAC) e imágenes gráficas . Se decide colocar las células madres adultas, previa valoración y preparación del paciente con el servicio de hematología y medicina transfusional. Se describe la conducta médico _ quirúrgica realizada y su diagnóstico anatomopatológico. Se presenta de forma gráfica la evolución clínico radiológico del paciente, inmediato, a los tres meses y a los dos años de evolución.
Resultados: quedó identificado que las células madres adultas inducen la regeneración ósea en las cavidades quísticas de los maxilares. Se discutió la evolución del paciente según la literatura consultada.
Conclusiones: Se puede expresar que lo identificado en este caso confirma el uso de células madres adultas en la regeneración ósea de cavidades quísticas de los
maxilares, además de abrir nuevas perspectivas en el tratamiento de otras afecciones del territorio maxilofacial como fracturas, artrosis de la ATM, defectos por lesiones oncológicas, por lo que se justifica la realización de proyectos investigativos que apoyen la utilización de esta nueva terapéutica.
DeCS: CÉLULAS MADRE, MEDICINA REGENERATIVA, QUISTE DENTÍGERO.
