Regeneración celular en los defectos óseos segmentarios

Introducción : Los defectos óseos segmentarios se producen por traumas de alta energía que ocasionan pérdida aguda de hueso, ocurren en forma subaguda durante el desbridamiento quirúrgico de una fractura expuesta y también pueden verse en casos crónicos como pseudoartrosis y osteomielitis, los que alteran la calidad de vida del paciente. Objetivo : Presentar un paciente con defecto óseo segmentario secundario a pseudoartrosis hipertrófica de húmero derecho de 6,3 cm. Caso clínico : Paciente masculino de 45 años de edad, raza blanca, sin antecedentes patológicos personales, que llega a nuestra consulta referido de otra institución de salud con diagnóstico de Pseudoartrosis hipertrófica de húmero derecho de tres años de evolución. Se realizó la técnica de inducción de membrana (Masquelet) la cual se combinó con la implantación de células madres adultas autólogas en el segundo tiempo quirúrgico. Se logró la consolidación ósea a las 12 semanas. Conclusiones: Dentro las variantes terapéuticas de los defectos óseos segmentarios se destaca la técnica de inducción de membrana que en combinación con el uso de la terapia celular constituye una opción prometedora, al necesitar un menor volumen de injerto, rápida consolidación además de una alternativa económica y de fácil elaboración sin gran complejidad tecnológica.

Introduction: Segmental bone defects are produced by high-energy traumas that cause acute bone loss, occur sub-acutely during surgical debridement of an exposed fracture, and can also be seen in chronic cases such as pseudarthrosis and osteomyelitis, drastically altering the quality of life of the patient. Objective: To present a patient with a segmental bone defect secondary to hypertrophic nonunion of the right humerus measuring 6.3 cm. Case report: A 45-year-old male patient, Caucasian, with no personal pathological history, who came to our office referred from another health institution with a diagnosis of hypertrophic pseudoarthrosis of the right humerus of 3 years of evolution. The membrane induction technique (Masquelet) is performed, which was combined with the implantation of autologous adult stem cells in the second surgical time. Bone union was achieved at 12 weeks. Conclusions: Within the therapeutic variants of the segmental bone defects, the membrane induction technique stands out, which in combination with the use of cell therapy constitutes a promising option, taking into account that a smaller graft volume is needed, rapid consolidation, as well as an economical alternative, and easy to make without great technological complexity.

Aplicación de células madres autólogas en pacientes con aterosclerosis obliterante grado IV / Application of autologous stem cells in patients with grade IV atherosclerosis obliterans

RESUMEN Introducción: la enfermedad arterial periférica de los miembros inferiores afecta a un elevado porcentaje de la población mundial, con las células madres autólogas obtenidas de sangre periférica se logra una mayor síntesis de factores de crecimiento que inducen la angiogénesis. Objetivo: describir el autotrasplante de células madres autólogas obtenidas de sangre periférica en pacientes con aterosclerosis obliterante grado IV, de Pinar del Río, atendidos en el período de 2009-2019. Métodos: se realizó un estudio descriptivo, longitudinal, con 296 pacientes que presentaban aterosclerosis obliterante grado IV durante en el período de 2009-2019. Se obtuvo el concentrado de células madres autólogas de sangre periférica. Las células se analizaron por citometría de flujo, donde mostraron una viabilidad celular del 99,3 %. Se les inyectó por vía intramuscular un concentrado de células madres con un número de células inyectadas de ocho, seis, diez. Las variables estudiadas fueron: índice de presión tobillo-brazo en reposo, distancia de claudicación libre de dolor, evaluación de la escala del dolor y criterio de amputación. Resultado: se observó alivio del dolor a las cuatro semanas y aumento de la distancia de claudicación libre de dolor. La angiografía post tratamiento mostró formación de vasos colaterales. Presentaron criterio de amputación 95 casos (32 %) se logró salvar la extremidad en 201 pacientes (68 %). El proceder realizado no se asoció con ninguna complicación. Conclusión: la aplicación de células madres autólogas de sangre periférica es segura y eficaz para el tratamiento de la aterosclerosis obliterante grado IV.

ABSTRACT Introduction: peripheral arterial disease of the lower limbs affects a high percentage of the world population; with autologous stem cells obtained from peripheral blood a greater synthesis of growth factors that induce angiogenesis is achieved. Objective: to describe the auto-transplantation of autologous stem cells obtained from peripheral blood in patients with grade IV atherosclerosis obliterans in Pinar del Rio treated during period 2009-2019. Methods: a descriptive, longitudinal study was carried out with 296 patients with grade IV atherosclerosis obliterans during the period 2009-2019. Autologous peripheral blood stem cell concentrate was obtained. The cells were analyzed by flow cytometry, where they showed a cell viability of 99,3 %. Stem cell concentrate was injected intramuscularly with a number of cells injected of eight, six and ten. The variables studied were ankle-brachial pressure index at rest, pain-free claudication distance, pain scale assessment and amputation criteria. Result: pain relief was observed at four weeks and increase in pain-free claudication distance. Post-treatment angiography showed collateral vessel formation. Amputation criteria were met in 95 cases (32 %) and the limb was saved in 201 patients (68 %). The procedure carried out was not associated with complications. Conclusion: the application of autologous peripheral blood stem cells is safe and effective for the treatment of grade IV atherosclerosis obliterans.

Report of a clinical and laboratory management of cell therapy for knee cartilage in the face of mycoplasma contamination

ABSTRACT To describe a case of autologous chondrocyte implantation after cell culture contamination by Mycoplasma pneumoniae and the measures taken to successfully complete cell therapy in a patient with focal chondral lesion. A 45-year-old male patient, complaining of chronic pain on the knee and no history of trauma. He had a chondral lesion in the trochlear region of the femur and clinical tests compatible with pain in the anterior compartment of the knee. Conservative treatment failed to alleviate symptoms. Surgical treatment was indicated, but due to the size of the lesion, membrane-assisted autologous chondrocyte implantation was the technique of choice. Cartilage biopsies were collected from the intercondylar region of the distal femur. After isolation, chondrocytes were expanded ex vivo in a trained laboratory, for three weeks, and seeded onto a commercially available collagen membrane prior to implantation in the knee. Two days before surgery, a cell culture sample tested positive for Mycoplasma pneumoniae. The source of contamination was found to be autologous blood serum, extracted from the patient´s peripheral vein, and used to supplement the cell culture medium. After treating the patient with antibiotics, all procedures were repeated and the new final cell product, free from contaminants, was successfully implanted. We discuss the strategies available to deal with this situation, and describe the results of this particular case, which led to modifications in the autologous chondrocyte implant protocol.

Matrix-assisted autologous chondrocyte transplantation for treatment of focal chondral lesions in the knee: the Hospital Israelita Albert Einstein experience

ABSTRACT Objective Phase 1 clinical trial to determine feasibility, safety, and efficacy of a new advanced cell therapy product for treatment of knee articular cartilage injuries. Methods Three participants with knee focal chondral lesions were included, with no signs of osteoarthritis. Chondrocytes were obtained through knee arthroscopy, cultured in collagen membrane for 3 weeks at the laboratory, subjected to tests to release the cell therapy product, and implanted. All patients underwent a specific 3-month rehabilitation protocol, followed by assessments using functional and imaging scales. The main outcome was the incidence of severe adverse events. Results Three participants were included and completed the 2-year follow-up. There was one severe adverse event, venous thrombosis of distal leg veins, which was no associated with therapy, was treated and left no sequelae. The clinical and radiological scales showed improvement in the three cases. Conclusion The preliminary results, obtained with the described methodology, allow concluding that this product of advanced cell therapy is safe and feasible. ReBEC platform registration number: RBR-6fgy76

Progress in treatment of bronchopulmonary dysplasia with exosomes / 中华围产医学杂志

Bronchopulmonary dysplasia (BPD) is a poor-prognosis disease. Stem cells may be the only treatment that can promote the repair and reconstruction of damaged lungs through secreting exosomes. Exosomes play crucial roles in anti-inflammatory, anti-apoptosis, anti-oxidation, inhibiting pulmonary fibrosis and promoting regeneration of damaged lung tissues, which are expected to be a new candidate for the prevention and treatment of BPD. This article reviews the research progress in the treatment of BPD with exosomes.

Limitations and advances in new treatments and future perspectives of corneal blindness / Limitações e avanços em novos tratamentos e perspectivas futuras na cegueira corneal

ABSTRACT This review is intended to describe the therapeutic approaches for corneal blindness, detailing the steps and elements involved in corneal wound healing. It also presents the limitations of the actual surgical and pharmacological strategies used to restore and maintain corneal transparency in terms of long-term survival and geographic coverage. In addition, we critically review the perspectives of anabolic agents, including vitamin A, hormones, growth factors, and novel promitotic and anti-inflammatory modulators, to assist corneal wound healing. We discuss the studies involving nanotechnology, gene therapy, and tissue reengineering as potential future strategies to work solely or in combination with corneal surgery to prevent or revert corneal blindness.(AU)

RESUMO O presente trabalho traz uma revisão das abordagens terapêuticas para a cegueira da córnea. O estudo detalha as etapas e os elementos envolvidos na cicatrização da córnea. Ele mostra as limitações das estratégias cirúrgicas e farmacológicas usadas para restaurar e manter a transparência da córnea em termos de sobrevida a longo prazo e alcance geográfico. As perspectivas dos agentes anabólicos, incluindo vitamina A, hormônios, fatores de crescimento e novos moduladores pró-mitóticos e anti-inflamatórios para auxiliar a cicatrização da ferida na córnea, são revisadas criticamente. Aqui, apresentamos estudos envolvendo nanotecnologia, terapia gênica e reengenharia de tecidos como possíveis estratégias futuras para atuar de maneira isolada ou combinada com a cirurgia da córnea para prevenir ou reverter a cegueira corneana.(AU)

Terapia con células madre e insuficiencia cardiaca: aspectos éticos / Ethics of stem cell therapy for heart failure

Heart failure is one of the first diseases in which stem cells were used for regenerative medicine. Since 2001, many publications have shown that stem cell therapy has the potential to mitigate heart diseases, but there is no solid scientific evidence to fully support its clinical application at present. The future of regenerative medicine requires validated clinical trials with standardized platforms and transdisciplinary efforts to enable the development of safe and effective regenerative therapies to protect patients and to promote the ethical application of this new and highly promising therapy. Doctors and scientists have a responsibility to discuss with patients the current reality of regenerative therapies. They also have a responsibility to discourage the indiscriminate and commercial use of these therapies, which are sometimes based on false hopes, since their inappropriate use can harm vulnerable patients as well as research efforts. Although regenerative medicine may be the medicine of the future and might bring the hope of cure for chronic diseases, it is not yet ready for its wide clinical application.

Effect of stem cells combined with a polymer/ceramic membrane on osteoporotic bone repair

Abstract Cell therapy associated with guided bone regeneration (GBR) can be used to treat bone defects under challenging conditions such as osteoporosis. This study aimed to evaluate the effect of mesenchymal stem cells (MSCs) in combination with a poly(vinylidene-trifluoroethylene)/barium titanate (PVDF-TrFE/BT) membrane on bone repair in osteoporotic rats. Osteoporosis was induced in female rats by bilateral removal of the ovaries (OVX) or sham surgery (SHAM), and the osteoporotic condition was characterized after 5 months by microtomographic and morphometric analyses. Calvarial defects were created in osteoporotic rats that immediately received the PVDF-TrFE/BT membrane. After 2 weeks, bone marrow-derived MSCs from healthy rats, characterized by the expression of surface markers using flow cytometry, or phosphate-buffered saline (PBS) (Control) were injected into the defects and bone formation was evaluated 4 weeks post-injection by microtomographic, morphometric, and histological analyses. A reduction in the amount of bone tissue in the femurs of OVX compared with SHAM rats confirmed the osteoporotic condition of the experimental model. More bone formation was observed when the defects were injected with MSCs compared to that with PBS. The modification that we are proposing in this study for the classical GBR approach where cells are locally injected after a membrane implantation may be a promising therapeutic strategy to increase bone formation under osteoporotic condition.

Feasibility of Cultured Allogenic Keratinocyte Treatment for Third Degree Burns

Tissue engineering perspectives in dentistry: review of the literature / Perspectivas da engenharia tecidual na Odontologia: revisão de literatura

ABSTRACT Tooth losses due to pathological processes continue to be a reality in daily clinical dentistry, inducing functional and psychological complications in patients. In view of this, a new option for the management of this problem - tissue engineering - has been studied in Dentistry. This field, considered multidisciplinary, uses three key elements for tissue regeneration: scaffolds (extracellular matrices) - natural or synthetic; cells, and growth factors. In this sense, combination of these three elements may induce regeneration of the dental pulp, bone and periodontal tissue, among others. Therefore, the aim of this study was to conduct a literature review, describing the main elements of tissue engineering and their applicability in Dentistry, as a means of updating dental surgeons about this subject.

RESUMO As perdas dentárias, devido aos processos patológicos, ainda são uma realidade na clínica odontológica diária, induzindo complicações funcionais e psicológicas ao paciente. Diante disso, uma nova opção para o manejo desse problema vem sendo estudada na Odontologia, a engenharia tecidual. Essa área, considerada multidisciplinar, utiliza três elementos chaves para a regeneração dos tecidos: os scaffolds (matriz extracelular) naturais ou sintéticos, as células e os fatores de crescimento. Nesse sentido, a combinação desses três elementos pode induzir a regeneração da polpa dentária, tecido ósseo e periodontal, entre outros. Portanto, o objetivo deste estudo é realizar uma revisão da literatura, descrevendo e atualizando os cirurgiões-dentistas sobre os principais elementos da engenharia tecidual e sua aplicabilidade na Odontologia.

Adipose tissue derived mesenchymal stem cell transplantation in the treatment of ischemia/reperfusion induced acute kidney injury in rats. Application route and therapeutic window

Abstract Purpose: To evaluate renal repair in rats who had renal infarction induced by the obstruction of blood flow in the renal artery and were treated with transplantation of adipose tissue derived mesenchymal stem cell Methods: 16-week-old Wistar rats (n=72) were used, submitted to celiotomy and had of the renal artery and vein clipped for 24 hours. The animals were randomly assigned to 10 experimental homogeneous groups, corresponding to the treatments with phosphate-buffered saline (PBS) or adipose tissue derived mesenchymal stem cell (ADSC), duration of application (24 or 48 hours), and site of transplantation (lateral vein of the tail or intrarenal). After the treatments were performed, at 8 and 31 days, four animals in each group were subjected to left nephrectomy for histological studies. Results: Histologically, a higher amount of cell debris and tubules devoid of the epithelium and a higher degree of necrosis were observed in the groups treated with PBS, as opposed to a low degree of necrosis and higher tubular vascularization in the groups treated with ADSC, particularly in the group treated with intrarenal ADSC 48 hours after injury. Conclusion: The transplantation of ADSC positively contributed to the replacement of necrotic tissue by renal tubular cells, vascularization of the renal parenchyma, and restoration of the organ function.

Terapia celular combinada com membranas de biopolímeros melhora a cicatrização de úlceras em paciente com dermatomiosite juvenil / Combining cell therapy with biopolymer films improves wound healing in a juvenile dermatomyositis patient

Introdução: Dermatomiosite juvenil (DMJ) é doença sistêmica que afeta a musculatura proximal e a pele de crianças. A doença ulcerada é um desafio terapêutico. Objetivo: Avaliar a melhora da doença ulcerada na DMJ, pelo uso de terapia celular. Métodos: Realização de cocultura de fibroblastos e queratinócitos autólogos e aplicação dessas células nas úlceras juntamente com cola de fibrina e colocação de membrana de quitosana-alginato ou quitosana-xantana sobre as lesões. Resultados: Menos de 12 horas após a terapia, o paciente referiu completa eliminação da dor e, dentro de dois dias, estava presente tecido de cicatrização. Algumas das úlceras estavam quase completamente cicatrizadas no final da primeira semana, e algumas das calcinoses desapareceram. Essa técnica não cura a doença, mas melhora a qualidade de vida, sendo possível criopreservar as células saudáveis do paciente para tratar novas lesões. Sendo as células de origem autóloga, elimina-se o risco de rejeição. Além disso, esse procedimento não necessita de debridamento das lesões nem hospitalização. Conclusões: A aplicação de culturas autólogas de fibroblastos e queratinócitos em úlceras já é considerada tratamento efetivo em pacientes com queimaduras e outras feridas cutâneas e, agora mostrou-se também eficaz no tratamento de feridas na DMJ.

Introduction: Juvenile dermatomyositis (JDM) is a systemic disease that affects children's proximal musculature and skin. The ulcerated stage of the disease is a therapeutic challenge. Objective: To evaluate the improvement of ulcerated stage of JDM caused by the use of cell therapy. Methods: Co-culture of autologous fibroblasts and keratinocytes, application of these cells in ulcers in conjunction with fibrin glue, and placement of chitosan-alginate or chitosan-xanthan membrane on the lesions. Results: Less than 12 hours after therapy, the patient reported complete cessation of pain and, within 2 days, healing tissue emerged. Some of the ulcers were almost completely healed by the end of the 1st week, and some of the calcinoses disappeared. This technique does not cure the disease, however it improves the patient's quality of life, and it is possible to cryopreserve healthy cells to treat new lesions. Given the fact that the cells are of autologous origin, the risk of rejection is eliminated. Furthermore, this procedure does not require debridement of the lesions or hospitalization. Conclusions: The application of autologous cultures of fibroblasts and keratinocytes in ulcers is already considered an effective treatment in patients with burns and other skin wounds, and has now also been proven effective in the treatment of wounds in JDM.

Cardiac Regeneration with Human Pluripotent Stem Cell-Derived Cardiomyocytes

Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), which are collectively called pluripotent stem cells (PSCs), have emerged as a promising source for regenerative medicine. Particularly, human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have shown robust potential for regenerating injured heart. Over the past two decades, protocols to differentiate hPSCs into CMs at high efficiency have been developed, opening the door for clinical application. Studies further demonstrated therapeutic effects of hPSC-CMs in small and large animal models and the underlying mechanisms of cardiac repair. However, gaps remain in explanations of the therapeutic effects of engrafted hPSC-CMs. In addition, bioengineering technologies improved survival and therapeutic effects of hPSC-CMs in vivo. While most of the original concerns associated with the use of hPSCs have been addressed, several issues remain to be resolved such as immaturity of transplanted cells, lack of electrical integration leading to arrhythmogenic risk, and tumorigenicity. Cell therapy with hPSC-CMs has shown great potential for biological therapy of injured heart; however, more studies are needed to ensure the therapeutic effects, underlying mechanisms, and safety, before this technology can be applied clinically.

Storage and use of cord blood

Cord blood (CB) has been used as an important source for hematopoietic stem cell transplantation and has been stored in public CB banks (CBBs) worldwide since the mid-1990s. Recently, the application of cell-based therapy using CB has expanded its clinical utility for various refractory diseases and immunologic diseases through the manufacture of mesenchymal stem cells or induced pluripotent stem cells and the isolation of mononuclear cells from CB. In this review, I briefly summarize the biologic characteristics and banking process of CB, as well as the current status of public and private CBBs. I also review the current status of stem cell transplantation and cell-based therapy using CBs. Finally, I suggest strategies of banking CBs in anticipation of future medical advances.

Bone-Marrow-Derived Mesenchymal Stromal Cells (MSC) from Diabetic and Nondiabetic Rats Have Similar Therapeutic Potentials / Células Estromais Mesenquimais (CEM) Derivadas de Medula Óssea de Ratos com e sem Diabetes têm Potencial Terapêutico Similar

Abstract Background: Diabetes mellitus is a severe chronic disease leading to systemic complications, including cardiovascular dysfunction. Previous cell therapy studies have obtained promising results with the use bone marrow mesenchymal stromal cells derived from healthy animals (MSCc) in diabetes animal models. However, the ability of MSC derived from diabetic rats to improve functional cardiac parameters is still unknown. Objectives: To investigate whether bone-marrow-derived MSC from diabetic rats (MSCd) would contribute to recover metabolic and cardiac electrical properties in other diabetic rats. Methods: Diabetes was induced in Wistar rats with streptozotocin. MSCs were characterized by flow cytometry, morphological analysis, and immunohistochemistry. Cardiac electrical function was analyzed using recordings of ventricular action potential. Differences between variables were considered significant when p < 0.05. Results: In vitro properties of MSCc and MSCd were evaluated. Both cell types presented similar morphology, growth kinetics, and mesenchymal profile, and could differentiate into adipogenic and osteogenic lineages. However, in an assay for fibroblast colony-forming units (CFU-F), MSCd formed more colonies than MSCc when cultured in expansion medium with or without hydrocortisone (1 µM). In order to compare the therapeutic potential of the cells, the animals were divided into four experimental groups: nondiabetic (CTRL), diabetic (DM), diabetic treated with MSCc (DM + MSCc), and diabetic treated with MSCd (DM + MSCd). The treated groups received a single injection of MSC 4 weeks after the development of diabetes. MSCc and MSCd controlled hyperglycemia and body weight loss and improved cardiac electrical remodeling in diabetic rats. Conclusions: MSCd and MSCc have similar in vitro properties and therapeutic potential in a rat model of diabetes induced with streptozotocin.

Resumo Fundamentos: O diabetes mellitus é uma doença crônica grave que leva a complicações sistêmicas, como a disfunção cardiovascular. Estudos anteriores de terapia celular obtiveram resultados promissores com utilização de células estromais mesenquimais (CEM) derivadas de medula óssea de animais saudáveis (CEMc) em modelos de animais diabéticos. No entanto, a capacidade das CEM derivadas de ratos diabéticos em melhorar parâmetros cardíacos funcionais é ainda desconhecida. Objetivos: Investigar se CEM derivadas de medula óssea de ratos diabéticos (CEMd) poderiam contribuir para a recuperação metabólica e de propriedades elétricas cardíacas em outros ratos também com diabetes. Métodos: O diabetes foi induzido em ratos Wistar com estreptozotocina. As CEM foram caracterizadas por citometria de fluxo, análise morfológica e imunohistoquímica. A função elétrica cardíaca foi analisada através de registro do potencial de ação ventricular. As diferenças entre as variáveis foram consideradas significativas quando p < 0,05. Resultados: As propriedades in vitro das CEMc e CEMd foram avaliadas. Ambos os tipos celulares apresentaram morfologia, cinética de crescimento e perfil mesenquimal semelhante, e puderam ser diferenciadas em linhagens adipogênica e osteogênica. No entanto, em ensaios para unidades formadoras de colônias de fibroblastos (UFC-F), as CEMd formaram mais colônias em comparação às CEMc quando cultivadas em meio com ou sem hidrocortisona (1 µM). Para comparar o potencial terapêutico das células, os animais foram divididos em quatro grupos experimentais: não diabéticos (CTRL), diabéticos (DM), diabéticos tratados com CEMc (DM + CEMc) e diabéticos tratados com CEMd (DM + CEMd). Os grupos tratados receberam uma única injeção de CEM 4 semanas após o estabelecimento do diabetes. Ambas CEMc e CEMd controlaram a hiperglicemia e a perda de peso corporal e melhoraram o remodelamento elétrico cardíaco em ratos com diabetes. Conclusão: As CEMd e CEMc possuem propriedades in vitro e potencial terapêutico semelhante em um modelo de rato com diabetes induzido por estreptozotocina. (Arq Bras Cardiol. 2017; 109(6):579-589)

Transplantation of human immature dental pulp stem cell in dogs with chronic spinal cord injury

Abstract Purpose: To investigate the therapeutic potential of human immature dental pulp stem cells in the treatment of chronic spinal cord injury in dogs. Methods: Three dogs of different breeds with chronic SCI were presented as animal clinical cases. Human immature dental pulp stem cells were injected at three points into the spinal cord, and the animals were evaluated by limb function and magnetic resonance imaging (MRI) pre and post-operative. Results: There was significant improvement from the limb function evaluated by Olby Scale, though it was not supported by the imaging data provided by MRI and clinical sign and evaluation. Conclusion: Human dental pulp stem cell therapy presents promising clinical results in dogs with chronic spinal cord injuries, if used in association with physical therapy.

Does mesenchymal stem cell improve the liver regeneration after the 70% hepatectomy?

Abstract Purpose: To evaluate the effects of mesenchymal stem cells on liver regeneration in rats following a 70% hepatectomy. Methods: Forty rats were subjected to 70% hepatectomy and then ~106 mesenchymal stem cells (test group), or saline solution (control group), were infused into their livers via the portal vein. Each treatment group was divided into early and late subgroups (euthanized 3 d and 5 d following the operation, respectively). Group comparisons of Albumin, aminotransaminases (AST, ALT), and Alcaline Phosphatase (AP) levels, proliferative index (ki-67+ straining), and mitotic cell counts were conducted. Results: No significant differences in liver regeneration rate, number of mitoses, proliferative index, or serum levels of albumin, AST, or AP were observed. ALT levels were higher in the test group than in the control group (p<.05). Conclusions: Mesenchymal stem-cell therapy did not improve liver regeneration rate 3 d or 5 d after 70% hepatectomy in rats. Likewise, the therapy appeared not to affect liver function, proliferative index, or number of mitoses significantly.

Traumatic spinal cord injury: current concepts and treatment update / Traumatismo raquimedular: conceitos atuais e atualizações terapêuticas

ABSTRACT Spinal cord injury (SCI) affects 1.3 million North Americans, with more than half occurring after trauma. In Brazil, few studies have evaluated the epidemiology of SCI with an estimated incidence of 16 to 26 per million per year. The final extent of the spinal cord damage results from primary and secondary mechanisms that start at the moment of the injury and go on for days, and even weeks, after the event. There is convincing evidence that hypotension contributes to secondary injury after acute SCI. Surgical decompression aims at relieving mechanical pressure on the microvascular circulation, therefore reducing hypoxia and ischemia. The role of methylprednisolone as a therapeutic option is still a matter of debate, however most guidelines do not recommend its regular use. Neuroprotective therapies aiming to reduce further injury have been studied and many others are underway. Neuroregenerative therapies are being extensively investigated, with cell based therapy being very promising.

RESUMO O traumatismo raquimedular (TRM) afeta 1.3 milhão de norte americanos, sendo mais da metade secundário a trauma.No Brasil, pouco estudos avaliaram sistematicamente a epidemiologia do TRM, mas estima-se uma incidência de 16 a 26 por milhão por ano. A extensão final do dano medular é resultante de mecanismos primários e secundários, que começam no momento do evento e prosseguem por dias e até semanas seguintes. Há fortes evidências de que a hipotensão contribua para danos secundários pós TRM. A cirurgia descompressiva visa a aliviar a compressão mecânica sobre a microcirculação, assim reduzindo isquemia e hipóxia. O papel da metilprednisolona no tratamento de pacientes com TRM é controverso, não sendo recomandada pela maior parte das diretrizes atuais. Terapias neuroprotetoras visando a reduzir injúria adicional foram e vêm sendo estudadas. Terapias neurorregenerativas estão sob investigação ampla, sendo a terapia celular uma forte promessa.

Opinión de médicos peruanos sobre la aplicación actual de terapias con células madre* / Peruvian doctor's opinion on the application of stem cell therapies

Objetivo: Conocer la opinión de un grupo de médicos peruanos sobre las características positivas y negativas acerca de los tratamientos con células madre que se realizan en clínicas del Perú y de otros países de Latinoamérica. La población está circunscrita a los médicos asistenciales que trabajan en diferentes hospitales, cualquiera que sea su especialidad. Materiales y métodos: Estudio descriptivo transversal. Se aplicó una encuesta a una muestra no probabilística de médicos peruanos. El cuestionario se construyó en base a las recomendaciones de la International Society for Stem Cell Research (ISSCR) en su Guidelines for the Clinical Translation of Stem Cells (Guía para la Traslación Clínica de las Células Madre). Resultados: Según nuestros resultados, la opinión de un grupo de médicos peruanos es que, en el Perú y Latinoamérica, se oferta la terapia con células madre para un gran número de dolencias, en primer lugar y con un importante porcentaje (30,9%) para las enfermedades neurodegenerativas. En la sección del cuestionario aplicado sobre estudios preclínicos, es importante el porcentaje en el que pocas veces o nunca se elimina el riesgo de producir tumores (38%). Respecto a la sección investigación clínica, llama la atención que en un 42% apenas o nunca tienen identificados los riesgos ni claros posibles beneficios de estas terapias. Conclusiones: Los médicos entrevistados consideran que se estaría ofertando terapias con células madre para tratar enfermedades muy diversas, entre las que destacan las neurodegenerativas, que en la actualidad son incurables y los posibles tratamientos están a nivel de ensayos clínicos, lo que no sería ético

Objective: To know the opinion of a group of Peruvian physicians about the positive and negative characteristics of stem cell therapies performed in clinics in Peru and other Latin American countries. The population is circumscribed to attending physicians working in different hospitals, whatever their specialty is. Materials and methods: This is a cross-sectional descriptive study. A survey was applied to a non-probabilistic sample of Peruvian physicians. The questionnaire was built based on the recommendations of the International Society for Stem Cell Research (ISSCR) set in its Guidelines for the Clinical Translation of Stem Cells. Results: According to our findings, the opinion of a group of Peruvian doctors is that in Peru and Latin America, stem cell therapy is offered for a large number of diseases, with a significant frequency (30.9%) for neurodegenerative diseases. In the section of the questionnaire with respect to preclinical studies, it is important to point out the percentage in which the risk of producing tumors (38%) is seldom or never eliminated. Regarding the clinical research section, it is noteworthy that in 42% the risks or clear potential benefits of these therapies have barely or never been identified. Conclusions: The interviewed physicians believe that stem cell therapies are offered for treating a wide variety of diseases, particularly neurodegenerative diseases, which are currently non-curable, and for which possible options of therapy are at the level of clinical trials, so it would not be ethical to offer stem cell therapies for such conditions

Cell Therapy Products in Alzheimer Disease

We are rapidly becoming an aging society, with the ongoing increase in challenges of the elderly. The age-related cognitive decline in accordance with aging society is of major importance in public health. Recent studies have proved the impacts of sex-steroid hormone on the brain; compliant with aging, menopause and decrease in estrogen have an effect on the occurrence and prevention of Alzheimer's disease. A new hypothesis states that Alzheimer's disease is a postmenopausal dementia, and is a negative form of estrogen deficiency. In this review article, we reckoned the cause of postmenopausal Alzheimer's disease. We further investigated new cell therapies for postmenopausal Alzheimer's disease, which are under development in some pharmaceutical companies. One remedy is cell therapy that inhibits the amyloid beta formation, and the other is the umbilical cord blood derived mesenchymal stem cell therapy.