Stem Cell Transplantation

This is a literature review about large granular lymphocyte leukemia (LGLL), a rare and misdiagnosed oncohematological disease, characterized by a clonal expansion of T-cells (T-LGLL) or NK-cells (NK-LGLL) in the bone marrow and/or peripheral blood. The clinical features of LGLL include cytopenias (anemia, neutropenia and thrombocytopenia), lymphocytosis (usually discrete), lymphadenopathy, hepatomegaly, splenomegaly, immune abnormalities and constitutional symptoms (fever, night sweats and weight loss). The diagnosis is based on the confirmation of the clonality of T-cells or NK-cells (polymerase chain reaction and Southern blot are the two methods most commonly used) and typical findings of the immunophenotypic analysis of peripheral blood lymphocytes (flow cytometry analyses for specific surface antigens). In contrast to the chronic and indolent course of T-LGLL, NK-LGLL has an acute presentation and poor clinical outcome. There are different current treatment options, depending on clinical presentation.

Epilepsy as one of the most common neurological disorders affects more than 50 million people worldwide with a higher prevalence rate in low-income countries. Excessive electrical discharges in neurons following neural cell damage or loss cause recurrent seizures. One of the most common and difficult to treat types of epilepsy is temporal lobe epilepsy (TLE) which results from hippocampal sclerosis. Nowadays, similar to other diseases, epilepsy also is a candidate for treatment with different types of stem cells. Various stem cell types were used for treatment of epilepsy in basic and experimental researches. Two major roles of stem cell therapy in epilepsy are prophylaxis against chronic epilepsy and amelioration cognitive function after the occurrence of TLE. Several animal studies have supported the use of these cells for treating drug-resistant TLE. Although stem cell therapy seems like a promising approach for treatment of epilepsy in the future however, there are some serious ...

O mieloma múltiplo (MM) é uma doença maligna de células plasmáticas incurável. O transplante de células-tronco hematopoéticas (TCTH) faz parte da estratégia terapêu-tica para a maioria dos pacientes. Devido à distribuição heterogênea dos centros de transplante no nosso país, os autores têm por objetivo descrever a experiência de um centro nordestino no tratamento desta entidade. De fevereiro de 2000 a dezembro de 2005 foram realizados e analisados de maneira prospectiva 21 TCTH autólogos para pacientes com MM no Hospital Português da Bahia. Epidemiologicamente houve pre-domínio do sexo feminino (1,6:1) e uma predominância de caucasianos (61,9%). A mediana de idade ao diagnóstico foi de 58 anos, sendo a maioria secretores de IgG (71,4%) que se apresentavam com estágio clínico IIIA (90,5%). A indicação para o procedimento foi a consolidação da remissão (RC) obtida inicialmente pela quimioterapia (52,4%) ou o resgate de uma doença refratária (47,6%). A taxa de sobrevida global (SG) foi de 74,7%, a taxa de sobrevida livre de doença (SLD) foi de 61,9% e a taxa de mortalidade (TM) foi de 5% nos primeiros cem dias. Quando avaliamos os pacientes transplantados em relação à fase da doença no momento do procedimento, observamos que aqueles transplantados em RC tiveram SG e SLD superiores àqueles não transplantados em RC (90,9% vs 64% e 68,2% vs 56%). Embora com uma epidemiologia peculiar, os resultados se mostraram semelhantes aos da literatura mundial, reforçando o fato de que o TCTH autólogo é fundamental na estratégia terapêutica contra o MM e está disponível no nordeste brasileiro. Rev. bras. hematol. hemoter. 2007;29(2):144-148. Palavras-chave: Mieloma múltiplo; transplante de células-tronco hematopoéticas; tratamento. Introdução O mieloma múltiplo (MM) é uma doença maligna peculiar que envolve não só as células plasmáticas que proliferam de forma clonal, mas também o microambiente medular. Epidemiologicamente, esta doença que acomete pacientes próximos da sexta década de vida é responsável por 1% de todos os tipos de câncer e por 10% das neoplasias hema-tológicas. Sua incidência é de aproximadamente 14 mil casos ao ano, sendo mais freqüente em negros do que em brancos,

Regenerative processes occurring under physiological (maintenance) and pathological (reparative) conditions are a fundamental part of life and vary greatly among different species, individuals, and tissues. Physiological regeneration occurs naturally as a consequence of normal cell erosion, or as an inevitable outcome of any biological process aiming at the restoration of homeostasis. Reparative regeneration occurs as a consequence of tissue damage. Although the central nervous system (CNS) has been considered for years as a “perennial” tissue, it has recently become clear that both physiological and reparative regeneration occur also within the CNS to sustain tissue homeostasis and repair. Proliferation and differentiation of neural stem/progenitor cells (NPCs) residing within the healthy CNS, or surviving injury, are considered crucial in sustaining these processes. Thus a large number of experimental stem cell-based transplantation systems for CNS repair have recently been establ...

The discovery of induced pluripotent stem cells (iPSCs) and the concurrent development of protocols for their cell-type-specific differentiation have revolutionized our approach to cell therapy. It has now become critical to address the challenges related to the generation of iPSCs under current good manufacturing practice (cGMP) compliant conditions, including tissue sourcing, manufacturing, testing, and storage. Furthermore, regarding the technical challenges, it is very important to keep the costs of manufacturing and testing reasonable and solve logistic hurdles that permit the global distribution of these products. Here we describe our efforts to develop a process for the manufacturing of iPSC master cell banks (MCBs) under cGMPs and announce the availability of such banks.

The use of granulocyte colony stimulating factor (G-CSF) biosimilars for peripheral blood hematopoietic stem cell (PBSC) mobilization has stimulated an ongoing debate regarding their efficacy and safety. However, the use of biosimilar G-CSF was approved by the European Medicines Agency (EMA) for all the registered indications of the originator G-CSF (Neupogen (®) ) including mobilization of stem cells. Here, we performed a comprehensive review of published reports on the use of biosimilar G-CSF covering patients with hematological malignancies as well as healthy donors that underwent stem cell mobilization at multiple centers using site-specific non-randomized regimens with a biosimilar G-CSF in the autologous and allogeneic setting. A total of 904 patients mostly with hematological malignancies as well as healthy donors underwent successful autologous or allogeneic stem cell mobilization, respectively, using a biosimilar G-CSF (520 with Ratiograstim®/Tevagrastim, 384 with Zarzio®)....

Chronic myelomonocytic leukemia is a heterogeneous hematologic malignancy classified among the mixed myelodysplastic/myeloproliferative diseases by the World Health Organization because of its myelodysplastic and myeloproliferative characteristics. In the proliferative form, diagnosis should include screening for known molecular abnormalities associated with constitutively active tyrosine kinases, which may be candidates for targeted therapies. Because patient life expectancy is highly variable and there is no consensus on optimal therapy, clinicians are advised to rely on a specific risk-oriented scoring system for clinical decision-making for individual patients. Although supportive care represents the milestone for disease management, novel active agents such as hypomethylating drugs recently have become available, so that the current therapeutic armamentarium now includes different treatment alternatives. Allogeneic stem cell transplantation may represent a curative option in hi...

To date, adult stem cell therapy has some achievements in the treatment of chronic disease. However, some risks in stem cell transplantation still serve as high barriers obstructing the pulling of these therapies into clinical use. Tumorigenecity is of almost concern after it is injected into patients. However, all clinical studies indexed in PubMed  showed that there were no cases of tumor after transplantation. Especially in recent study published in Cell Death and Disease, Wang et al. (2013) showed that long-term cultured mesenchymal stem cells could develop the genomic mutations but cannot undergo malignant transformation. Moreover, the study also revealed these stem cells as capable of forming tumors. This commentary assesses the data generated to date, and discusses the conclusions drawn from various studies.

Although the prognosis for mantle cell lymphoma (MCL) patients has improved in recent years, the outlook for those with advanced or recurrent disease remains poor. High-dose chemotherapy and autografting performed early in responding patients appears to be a method to extend progression-free survival (PFS) and overall survival (OS). The use of monoclonal antibody therapy added into the initial therapy and

Parkinson's disease (PD) affects one in every 100 persons above the age of 65 years, making it the second most common neurodegenerative disease after Alzheimer's disease. PD is a disease of the central nervous system that leads to severe difficulties with body motions. The currently available therapies aim to improve the functional capacity of the patient for as long as possible; however they do not modify the progression of the neurodegenerative process. The need for newer and more effective agents is consequently receiving a great deal of attention and consequently being subjected to extensive research. This review concisely compiles the limitations of currently available therapies and the most recent research regarding neuroprotective agents, antioxidants, stem cell research, vaccines and various surgical techniques available and being developed for the management of PD.

Functions of hematopoietic stem cells (HSCs) are tightly regulated to ensure lifelong normal hematopoiesis within the bone marrow (BM) niche. While HSCs' status is well orchestrated to uphold their stemness, the fate of HSCs can be altered in response to inflammatory signals caused by environmental changes. The influence on HSCs of inflammatory changes within BM has been explored; however, how each inflammatory cytokine affects the maintenance or differentiation of HSCs remains to be fully elucidated. Considering recent studies demonstrating that reactive oxygen species (ROS) influence HSCs' fates, we conducted a comprehensive analysis of the effects of seven major inflammatory cytokines on proliferation, differentiation, and ROS level regulation in HSCs / hematopoietic stem/progenitor cells (HSPCs). Our study indicates that inflammatory cytokines in general push HSCs/HSPCs into differentiation, but vary significantly with respect to retention of primitive cells. With definition by cellular immunophenotypes, TNF-α, IFN-γ, and type I IFNs stimulated loss of HSCs, whereas TGF-β and IL-6, and possibly IL-1β as well, showed potential to retain them. Of note is that unaltered ROS levels were compatible with HSC retention, while drastic change, either increase or decrease, in ROS levels presaged HSC loss. Detailed evaluation of links between inflammatory cytokines and ROS regulation appears likely to prove important in understanding HSC biology and translating basic science into clinical applications.

The dynamic nature of modern warfare, including threats and injuries faced by soldiers, necessitates the development of countermeasures that address a wide variety of injuries. Tissue engineering has emerged as a field with the potential to provide contemporary solutions. In this review, discussions focus on the applications of stem cells in tissue engineering to address health risks frequently faced by combatants at war. Human development depends intimately on stem cells, the mysterious precursor to every kind of cell in the body that, with proper instruction, can grow and differentiate into any new tissue or organ. Recent reports have suggested the greater therapeutic effects of the anti-inflammatory, trophic, paracrine and immune-modulatory functions associated with these cells, which induce them to restore normal healing and tissue regeneration by modulating immune reactions, regulating inflammation, and suppressing fibrosis. Therefore, the use of stem cells holds significant pr...