Bone Marrow-Derived Mononuclear Cell Therapy Accelerates Renal Ischemia-Reperfusion Injury Recovery by Modulating Inflammatory, Antioxidant and Apoptotic Related Molecules.

BACKGROUND/AIMS: We investigated the regenerative capacity of intravenous administration of bone marrow-derived mononuclear cells (BMMCs) in a rat model of bilateral renal ischemia/reperfusion (IR) injury and the involvement of inflammatory anti-inflammatory and other biological markers in this process. METHODS: Rats were subjected to 1h bilateral renal pedicle clamping. BMMCs were injected i.v 1h after reperfusion and tracked by 99mTc and GFP+ BMMCs. Twenty-four hours after reperfusion, renal function and histological changes were evaluated. The mRNA (real time PCR) and protein (ELISA and immuno-staining) expression of biological markers were analyzed. RESULTS: Renal function and structure improved after infusion of BMMCs in the IR group (IR-C). Labeled BMMCs were found in the kidneys after therapy. The expression of inflammatory and biological markers (TLR-2, TRL-4, RAGE, IL-17, HMGB-1, KIM-1) were reduced and the expression of anti-inflammatory and antioxidant markers (IL-10, Nrf2, and HO-1) were increased in IR-C animals compared with IR untreated animals (IR-S). The apoptotic index diminished and the proliferation index increased in IR-C compared with IR-S. CONCLUSION: The results contribute to our understanding of the role of different biological players in morphofunctional renal improvement and cytoprotection in a post-ischemic reperfusion kidney injury model subjected to cellular therapy.

Mesenchymal Stromal Cells Induce Podocyte Protection in the Puromycin Injury Model.

Podocytes are specialized cells with a limited capacity for cell division that do not regenerate in response to injury and loss. Insults that compromise the integrity of podocytes promote proteinuria and progressive renal disease. The aim of this study was to evaluate the potential renoprotective and regenerative effects of mesenchymal stromal cells (mSC) in a severe form of the podocyte injury model induced by intraperitoneal administration of puromycin, aggravated by unilateral nephrectomy. Bone derived mSC were isolated and characterized according to flow cytometry analyses and to their capacity to differentiate into mesenchymal lineages. Wistar rats were divided into three groups: Control, PAN, and PAN+ mSC, consisting of PAN rats treated with 2 × 105 mSC. PAN rats developed heavy proteinuria, hypertension, glomerulosclerosis and significant effacement of the foot process. After 60 days, PAN rats treated with mSC presented a significant amelioration of all these abnormalities. In addition, mSC treatment recovered WT1 expression, improved nephrin, podocin, synaptopodin, podocalyxin, and VEGF expression, and downregulated proinflammatory Th1 cytokines in the kidney with a shift towards regulatory Th2 cytokines. In conclusion, mSC administration induced protection of podocytes in this experimental PAN model, providing new perspectives for the treatment of renal diseases associated with podocyte damage.

Imunodeficiência combinada grave: uma revisão da literatura / Severe combined immunodeficiency: review of the literature

A imunodeficiência combinada grave (SCID) é uma condição clínica caracterizada por marcante comprometimento da resposta imune envolvendo linfócitos T e/ou B e/ou células NK, que conduza aumento da susceptibilidade a infecções e alta taxa de mortalidade em crianças acometidas. Dificuldades na interpretação dos sintomas clínicos e na identificação de mutações genéticas, devido à ampla variedade fenotípica e genotípica da doença, representam obstáculos para o diagnóstico. Por outro lado, o tratamento é realizado de forma independente da identificação de mutação genética. O objetivo do presente trabalho foi revisar aspectos fisiopatológicos, métodos diagnósticos e tratamentos utilizados em pacientes com SCID. A revisão foi realizada com base em levantamento bibliográfico de banco de dados indexados disponíveis na Internet incluindo LILACS, MEDLINE, PubMed, SciELO Brasil, periódicos CAPES e Cochrane, e foi conduzida com os seguintes critérios de inclusão: artigos científicos publicados nos idiomas português e inglês, dentro do período de 1963 a 2014 e que possuíam as palavras-chave “Imunodeficiência Combinada Grave”, “SCID”, “Leucopenia”, “Diagnóstico”, “Tratamento” e “Transplante de medula óssea”. O levantamento bibliográfico revelou dificuldades no diagnóstico clínico, laboratorial e genético-molecular, e ressaltou a importância do diagnóstico precoce conduzindo ao tratamento adequado. O diagnóstico precoce da SCID tem papel crucial na melhora da qualidade de vida e na sobrevida dos pacientes, além de favorecer intervenções terapêuticas que previnem o surgimento de infecções e complicações clínicas subsequentes...

Severe combined immunodeficiency (SCID) is a clinical condition characterized by marked impairment of immune responses involving T and/or B lymphocytes and/or NK cells, leading to increased susceptibility to infections and a high mortality rate among affected infants. Difficulties in the interpretation of clinical symptoms and in the detection of genetic mutations make diagnosis a challenge because of the phenotypic and genotypic heterogeneity associated with the disease. Treatment is performed regardless of the detection of a genetic mutation. The objective of the present study was to review pathophysiological aspects, diagnostic methods, and therapies used in patients with SCID. The review included papers available in online databases, including LILACS, MEDLINE, PubMed, SciELO Brazil, Periódicos CAPES, and Cochrane. Papers were searched considering the following inclusion criteria: research articles published in Portuguese or English, between years 1963 and 2014, containing the keywords "Severe Combined Immunodeficiency," "SCID," "Leukopenia," "Diagnosis," "Treatment," and "Bone Marrow Transplantation." The review revealed difficulties in clinical, biochemical, and molecular genetic diagnosis, and emphasized the importance of early diagnosis leading to appropriate treatment. Early diagnosis of SCID is crucial to improve the quality of life and survival of patients, and it allows the use of therapeutic interventions that prevent the onset of infections and subsequent clinical complications...