TLR4 and NLRP3 Caspase 1- IL-1β- Axis are not Involved in Colon Ascendens Stent Peritonitis (Casp)-Associated Heart Disease

Hemodynamic collapse and myocardial dysfunction are among the major causes ofdeath in severe sepsis. The purpose of this study was to assess the role played by TLR4and by the NLRP3 inflammasome in the cardiac dysfunction that occurs after highgradepolymicrobial sepsis. We performed the colon ascendens stent peritonitis (CASP)surgery in Tlr4-/-, Nlrp3-/- and caspase-1-/- mice. We also assessed for the first time theelectrical heart function in the CASP model. The QJ interval was increased in wild-typeC57BL/6J mice after CASP when compared to sham controls, a result paralleled by anincrease in the cardiac action potential duration (APD). The decreases in ejectionfraction (EF), left-ventricle end diastolic volume (LVEDV), stroke volume, and cardiacoutput found after CASP were similar among all groups of mice. Similar heart responsewas found when Nlrp3-/- mice were submitted to high-grade CLP. Despite developingcardiac dysfunction similar to wild-types after CASP, Nlrp3-/- mice had reducedcirculating levels of IL-1β, IL-6 and TNF-α. Our results demonstrate that the geneticablation of Tlr4, Nlrp3, and caspase-1 does not prevent the cardiac dysfunction, despitepreventing the increase in pro-inflammatory cytokines, indicating that these are notfeasible targets to therapy in high-grade sepsis.Fil: López Alarcón, Maria Micaela. Universidade Federal do Rio de Janeiro; BrasilFil: Fernandez Ruocco, Maria Julieta. Universidade Federal do Rio de Janeiro; BrasilFil: Ferreira, Fabiano. Universidade Federal do Rio de Janeiro; BrasilFil: Paula Neto, Heitor A.. Universidade Federal do Rio de Janeiro; BrasilFil: Sepúlveda, Marisa Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Investigaciones Cardiovasculares ; ArgentinaFil: Vila Petroff, Martin Gerarde. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Investigaciones Cardiovasculares ; ArgentinaFil: Carvalho, Adriana Bastos. Universidade Federal do Rio de Janeiro; BrasilFil: Peroba Ramos, Isalira. Universidade Federal do Rio de Janeiro; BrasilFil: Branda, Hugo Justino. Universidade Federal do Rio de Janeiro; BrasilFil: Neto Paiva, Claudia. Universidade Federal do Rio de Janeiro; BrasilFil: Medei, Emiliano. Universidade Federal do Rio de Janeiro; Brasi

Echocardiographic measurements in a preclinical model of chronic chagasic cardiomyopathy in dogs : validation and reproducibility.

Background: The failure to translate preclinical results to the clinical setting is the rule, not the exception. One reason that is frequently overlooked is whether the animal model reproduces distinctive features of human disease. Another is the reproducibility of the method used to measure treatment effects in preclinical studies. Left ventricular (LV) function improvement is the most common endpoint in preclinical cardiovascular disease studies, while echocardiography is the most frequently used method to evaluate LV function. In this work, we conducted a robust echocardiographic evaluation of LV size and function in dogs chronically infected by Trypanosoma cruzi. Methods and Results: Echocardiography was performed blindly by two distinct observers in mongrel dogs before and between 6 and 9 months post infection. Parameters analyzed included end-systolic volume (ESV), end-diastolic volume (EDV), ejection fraction (EF), and fractional shortening (FS). We observed a significant LVEF and FS reduction in infected animals compared to controls, with no significant variation in volumes. However, the effect of chronic infection in systolic function was quite variable, with EF ranging from 17 to 66%. Using the cut-off value of EF ? 40%, established for dilated cardiomyopathy (DCM) in dogs, only 28% of the infected dogs were affected by the chronic infection. Conclusions: The canine model of CCC mimics human disease, reproducing the percentage of individuals that develop heart failure during the chronic infection. It is thus mandatory to establish inclusion criteria in the experimental design of canine preclinical studies to account for the variable effect that chronic infection has on systolic function

A divulgação científica em tempos de pandemia

A divulgação científica é um desafio para a ciência em todo o mundo. Em tempos de pandemia, o ato de conscientizar a população sobre a importância da ciência se tornou ímpar. O CENABIO/UFRJ é um centro multiusuário, multidisciplinar com infraestrutura e parque de equipamentos único na América Latina. Oferecendo suporte técnico-científico e acadêmico a cientistas de todo o país, permitindo o desenvolvimento de projetos de caráter multidisciplinar na fronteira do conhecimento que podem ir da molécula ao organismo inteiro. Além de constituir um centro de referência na pesquisa biomédica, o CENABIO também cumpre seu papel na educação e divulgação da ciência ao grande público. Possuindo um Núcleo de Educação e Divulgação Científica - NEDiCi, que é responsável pela criação de atividades de divulgação científica. Dentro desse contexto, o NEDiCi, já realizou diversas ações recebendo alunos nas dependências do CENABIO e levando oficinas até as escolas. Em tempos de pandemia, esse núcleo passou a exercer suas atividades de forma remota. E uma das grandes questões foi a de como transpor visitas presenciais em oficinas remotas. Tendo como contexto a disseminação crescente de fake News durante o período de pandemia e desenvolvimento das vacinas contra o SARS-CoV2, foi montada uma oficina lúdica e dinâmica contendo informações acerca da Covid-19 para ser ministrada online por plataformas de videoconferência para o público infantojuvenil. Durante a realização da oficina foi estimulado o pensamento crítico dos jovens participantes e o debate através de afirmações, que poderiam ser verdadeiras ou falsas, acerca da Covid-19 e do SARS-Cov2. Os participantes deveriam debater com os colegas e chegar a um consenso sobre se as afirmações eram fatos ou fakes e explicar o porquê. Após a exposição das justificativas pelos participantes, os facilitadores expunham as explicações sobre as afirmativas e as debatiam. O objetivo desta oficina foi o de conscientizar o público infantojuvenil acerca da qualidade da informação veiculada na internet, nas mídias sociais e aplicativos de comunicação. Demonstrar que toda a informação precisa ser obtida a partir de uma fonte confiável e analisar quais podem ser consideradas fontes confiáveis, além de muni-los com informações corretas e atualizadas sobre a Covid-19. Foi considerado que essas informações foram repassadas com êxito para as crianças de maneira lúdica e leve para que elas possam agir na prática, da maneira mais segura para todos, além de estimular o pensamento crítico-científico e trabalho em equipe

Pentoxifylline Reverses Chronic Experimental Chagasic Cardiomyopathy in Association with Repositioning of Abnormal CD8+ T-Cell Response

Submitted by sandra infurna ([email protected]) on 2016-04-28T14:57:30Z No. of bitstreams: 1 isabela_pereira_etal_IOC_2015.pdf: 6043084 bytes, checksum: 03af83923a25cfd4e95c3be608b6e3b2 (MD5)Approved for entry into archive by sandra infurna ([email protected]) on 2016-04-28T15:07:54Z (GMT) No. of bitstreams: 1 isabela_pereira_etal_IOC_2015.pdf: 6043084 bytes, checksum: 03af83923a25cfd4e95c3be608b6e3b2 (MD5)Made available in DSpace on 2016-04-28T15:07:54Z (GMT). No. of bitstreams: 1 isabela_pereira_etal_IOC_2015.pdf: 6043084 bytes, checksum: 03af83923a25cfd4e95c3be608b6e3b2 (MD5) Previous issue date: 2015Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Cardiologia Celular e Molecular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil.BACKGROUND: Chronic chagasic cardiomyopathy (CCC), the main clinical sign of Chagas disease, is associated with systemic CD8+ T-cell abnormalities and CD8-enriched myocarditis occurring in an inflammatory milieu. Pentoxifylline (PTX), a phosphodiesterase inhibitor, has immunoregulatory and cardioprotective properties. Here, we tested PTX effects on CD8+ T-cell abnormalities and cardiac alterations using a model of experimental Chagas' heart disease. METHODOLOGY/PRINCIPAL FINDINGS: C57BL/6 mice chronically infected by the Colombian Trypanosoma cruzi strain and presenting signs of CCC were treated with PTX. The downmodulation of T-cell receptors on CD8+ cells induced by T. cruzi infection was rescued by PTX therapy. Also, PTX reduced the frequency of CD8+ T-cells expressing activation and migration markers in the spleen and the activation of blood vessel endothelial cells and the intensity of inflammation in the heart tissue. Although preserved interferon-gamma production systemically and in the cardiac tissue, PTX therapy reduced the number of perforin+ cells invading this tissue. PTX did not alter parasite load, but hampered the progression of heart injury, improving connexin 43 expression and decreasing fibronectin overdeposition. Further, PTX reversed electrical abnormalities as bradycardia and prolonged PR, QTc and QRS intervals in chronically infected mice. Moreover, PTX therapy improved heart remodeling since reduced left ventricular (LV) hypertrophy and restored the decreased LV ejection fraction. CONCLUSIONS/SIGNIFICANCE: PTX therapy ameliorates critical aspects of CCC and repositioned CD8+ T-cell response towards homeostasis, reinforcing that immunological abnormalities are crucially linked, as cause or effect, to CCC. Therefore, PTX emerges as a candidate to treat the non-beneficial immune deregulation associated with chronic Chagas' heart disease and to improve prognosis

CCL3/Macrophage Inflammatory Protein-1α Is Dually Involved in Parasite Persistence and Induction of a TNF- and IFNγ-Enriched Inflammatory Milieu in Trypanosoma cruzi-Induced Chronic Cardiomyopathy

Submitted by Sandra Infurna ([email protected]) on 2020-03-29T17:24:07Z No. of bitstreams: 1 JoseliLVieira_GlauciaPereira_etal_IOC_2020.pdf: 4148062 bytes, checksum: 271051d3a2e4d93789b5f0c58b65f292 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2020-03-29T17:46:56Z (GMT) No. of bitstreams: 1 JoseliLVieira_GlauciaPereira_etal_IOC_2020.pdf: 4148062 bytes, checksum: 271051d3a2e4d93789b5f0c58b65f292 (MD5)Made available in DSpace on 2020-03-29T17:46:56Z (GMT). No. of bitstreams: 1 JoseliLVieira_GlauciaPereira_etal_IOC_2020.pdf: 4148062 bytes, checksum: 271051d3a2e4d93789b5f0c58b65f292 (MD5) Previous issue date: 2020Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil.Universidade Federal Fluminense. Faculdade de Medicina. Departamento de Patologia. Laboratório de Hematologia. Niterói, RJ, Brasil.Universidade Federal Fluminense. Faculdade de Medicina. Departamento de Patologia. Laboratório Multiusuário de Apoio à Pesquisa em Nefrologia e Ciências Médicas. Niterói, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Cardiologia Celular e Molecular. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro; Centro de Ciências da Saúde. Centro Nacional de Biologia Estrutural e Bioimagem. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. Rio de Janeiro, RJ, Brasil.Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil.CCL3, a member of the CC-chemokine family, has been associated with macrophage recruitment to heart tissue and parasite control in the acute infection of mouse with Trypanosoma cruzi, the causative agent of Chagas disease. Here, we approached the participation of CCL3 in chronic chagasic cardiomyopathy (CCC), the main clinical form of Chagas disease. We induced CCC in C57BL/6 (ccl3+/+) and CCL3-deficient (ccl3-/-) mice by infection with the Colombian Type I strain. In ccl3+/+ mice, high levels of CCL3 mRNA and protein were detected in the heart tissue during the acute and chronic infection. Survival was not affected by CCL3 deficiency. In comparison with ccl3+/+, chronically infected ccl3-/- mice presented reduced cardiac parasitism and inflammation due to CD8+ cells and macrophages. Leukocytosis was decreased in infected ccl3-/- mice, paralleling the accumulation of CD8+ T cells devoid of activated CCR5+ LFA-1+ cells in the spleen. Further, T. cruzi-infected ccl3-/-mice presented reduced frequency of interferon-gamma (IFNγ)+ cells and numbers of parasite-specific IFNγ-producing cells, while the T. cruzi antigen-specific cytotoxic activity was increased. Stimulation of CCL3-deficient macrophages with IFNγ improved parasite control, in a milieu with reduced nitric oxide (NOx) and tumor necrosis factor (TNF), but similar interleukin-10 (IL-10), concentrations. In comparison with chronically T. cruzi-infected ccl3+/+ counterparts, ccl3-/- mice did not show enlarged heart, loss of left ventricular ejection fraction, QTc prolongation and elevated CK-MB activity. Compared with ccl3+/+, infected ccl3-/- mice showed reduced concentrations of TNF, while IL-10 levels were not affected, in the heart milieu. In spleen of ccl3+/+ NI controls, most of the CD8+ T-cells expressing the CCL3 receptors CCR1 or CCR5 were IL-10+, while in infected mice these cells were mainly TNF+. Lastly, selective blockage of CCR1/CCR5 (Met-RANTES therapy) in chronically infected ccl3+/+ mice reversed pivotal electrical abnormalities (bradycardia, prolonged PR, and QTc interval), in correlation with reduced TNF and, mainly, CCL3 levels in the heart tissue. Therefore, in the chronic T. cruzi infection CCL3 takes part in parasite persistence and contributes to form a CD8+ T-cell and macrophage-enriched cardiac inflammation. Further, increased levels of CCL3 create a scenario with abundant IFNγ and TNF, associated with cardiomyocyte injury, heart dysfunction and QTc prolongation, biomarkers of severity of Chagas' heart disease

Pentoxifylline Reverses Chronic Experimental Chagasic Cardiomyopathy in Association with Repositioning of Abnormal CD8⁺ T-Cell Response

<div><p>Background</p><p>Chronic chagasic cardiomyopathy (CCC), the main clinical sign of Chagas disease, is associated with systemic CD8⁺ T-cell abnormalities and CD8-enriched myocarditis occurring in an inflammatory milieu. Pentoxifylline (PTX), a phosphodiesterase inhibitor, has immunoregulatory and cardioprotective properties. Here, we tested PTX effects on CD8⁺ T-cell abnormalities and cardiac alterations using a model of experimental Chagas’ heart disease.</p><p>Methodology/Principal Findings</p><p>C57BL/6 mice chronically infected by the Colombian <i>Trypanosoma cruzi</i> strain and presenting signs of CCC were treated with PTX. The downmodulation of T-cell receptors on CD8⁺ cells induced by <i>T</i>. <i>cruzi</i> infection was rescued by PTX therapy. Also, PTX reduced the frequency of CD8⁺ T-cells expressing activation and migration markers in the spleen and the activation of blood vessel endothelial cells and the intensity of inflammation in the heart tissue. Although preserved interferon-gamma production systemically and in the cardiac tissue, PTX therapy reduced the number of perforin⁺ cells invading this tissue. PTX did not alter parasite load, but hampered the progression of heart injury, improving connexin 43 expression and decreasing fibronectin overdeposition. Further, PTX reversed electrical abnormalities as bradycardia and prolonged PR, QTc and QRS intervals in chronically infected mice. Moreover, PTX therapy improved heart remodeling since reduced left ventricular (LV) hypertrophy and restored the decreased LV ejection fraction.</p><p>Conclusions/Significance</p><p>PTX therapy ameliorates critical aspects of CCC and repositioned CD8⁺ T-cell response towards homeostasis, reinforcing that immunological abnormalities are crucially linked, as cause or effect, to CCC. Therefore, PTX emerges as a candidate to treat the non-beneficial immune deregulation associated with chronic Chagas' heart disease and to improve prognosis.</p></div

Divulgação científica em tempos de pandemia: a importância de divulgar o fato em meio às fakes

A divulgação científica é uma forma de atrair o público infantojuvenil para a ciência desde cedo. Diante da pandemia atual, a sociedade foi bombardeada com informações sobre uma doença nova e de como se comportar perante ela. Entretanto, muitas dessas informações são falsas ou incompletas, levando a um julgamento errôneo. No intuito de divulgar a ciência, utilizando o contexto da pandemia de Covid-19, foi criada uma oficina virtual com estudantes entre 8-12 anos que foram expostos a afirmações sobre essa pandemia e após eles exporem suas opiniões, nossos facilitadores revelavam as respostas, justificando cada uma delas. Assim, a oficina cumpriu seu papel de informar as crianças de maneira lúdica e leve sobre a pandemia que enfrentamos, de modo a muni-las de conhecimento confiável para que possam agir na prática da maneira mais segura, além de estimular o pensamento científico e trabalho em equipe

Calcium/Calmodulin Protein Kinase II-Dependent Ryanodine Receptor Phosphorylation Mediates Cardiac Contractile Dysfunction Associated with Sepsis

Objectives: Sepsis is associated with cardiac contractile dysfunction attributed to alterations in Ca2+ handling. We examined the subcellular mechanisms involved in sarcoplasmic reticulum Ca2+ loss that mediate altered Ca2+ handling and contractile dysfunction associated with sepsis. Design: Randomized controlled trial. Setting: Research laboratory Subjects: Male wild type and transgenic mice Interventions: We induced sepsis in mice using the colon ascendens stent peritonitis model. Measurements and Main Results: Twenty-four hours after colon ascendens stent peritonitis surgery, we observed that wild type mice had significantly elevated proinflammatory cytokine levels, reduced ejection fraction, and fractional shortening (ejection fraction %, 54.76 ± 0.67; fractional shortening %, 27.53 ± 0.50) compared with sham controls (ejection fraction %, 73.57 ± 0.20; fractional shortening %, 46.75 ± 0.38). At the cardiac myocyte level, colon ascendens stent peritonitis cells showed reduced cell shortening, Ca2+ transient amplitude and sarcoplasmic reticulum Ca2+ content compared with sham cardiomyocytes. Colon ascendens stent peritonitis hearts showed a significant increase in oxidation-dependent calcium and calmodulin-dependent protein kinase II activity, which could be prevented by pretreating animals with the antioxidant tempol. Pharmacologic inhibition of calcium and calmodulin-dependent protein kinase II with 2.5 μM of KN93 prevented the decrease in cell shortening, Ca2+ transient amplitude, and sarcoplasmic reticulum Ca2+ content in colon ascendens stent peritonitis myocytes. Contractile function was also preserved in colon ascendens stent peritonitis myocytes isolated from transgenic mice expressing a calcium and calmodulin-dependent protein kinase II inhibitory peptide (AC3-I) and in colon ascendens stent peritonitis myocytes isolated from mutant mice that have the ryanodine receptor 2 calcium and calmodulin-dependent protein kinase II-dependent phosphorylation site (serine 2814) mutated to alanine (S2814A). Furthermore, colon ascendens stent peritonitis S2814A mice showed preserved ejection fraction and fractional shortening (ejection fraction %, 73.06 ± 6.31; fractional shortening %, 42.33 ± 5.70) compared with sham S2814A mice (ejection fraction %, 71.60 ± 4.02; fractional shortening %, 39.63 ± 3.23). Conclusions: Results indicate that oxidation and subsequent activation of calcium and calmodulin-dependent protein kinase II has a causal role in the contractile dysfunction associated with sepsis. Calcium and calmodulin-dependent protein kinase II, through phosphorylation of the ryanodine receptor would lead to Ca2+ leak from the sarcoplasmic reticulum, reducing sarcoplasmic reticulum Ca2+ content, Ca2+ transient amplitude and contractility. Development of organ-specific calcium and calmodulin-dependent protein kinase II inhibitors may result in a beneficial therapeutic strategy to ameliorate contractile dysfunction associated with sepsis.Fil: Sepúlveda, Marisa Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Gonano, Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Viotti, Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Morell, Malena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Blanco, Paula Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: López Alarcón, Maria Micaela. Universidade Federal do Rio de Janeiro; BrasilFil: Peroba Ramos, Isalira. Universidade Federal do Rio de Janeiro; BrasilFil: Bastos Carvalho, Adriana. Universidade Federal do Rio de Janeiro; BrasilFil: Medei, Emiliano. Universidade Federal do Rio de Janeiro; BrasilFil: Vila Petroff, Martin Gerarde. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentin

Safety and Localization of Mesenchymal Stromal Cells Derived from Human Adipose Tissue-Associated Hyaluronic Acid: A Preclinical Study

Millions of plastic surgeries are performed worldwide every year with the objective of correcting lipodystrophies stemming from lesions, tumor resections, birth defects, and AIDS-associated antiretroviral therapy. Besides that, a large number of clinical research have assessed the outcome of procedures that rely on combinations of dermal fillers and autologous cells. However, little is known about the safety of these combinations and the localization of the injected cells. The aim of this study was to test the toxicity of a solution containing 1% hyaluronic acid (HA) and adipose-derived stromal cells (ASCs) from the human adipose tissue and to assess the localization of the injected cells, with and without HA, labeled with technetium-99m. Rats received subcutaneous and intraperitoneal injections of a solution containing 1% HA/adipose-derived stromal cells isolated from the human fat tissue. The animals were then observed for up to forty-two days. The solution tested in this study did not result in systemic, biochemical, or anatomic alterations that could represent toxicity symptoms. The association of HA and ASCs labeled with technetium-99m remained at the site of the injection within a period of twenty-four hours, as demonstrated by a whole-body imaging software fusion of SPECT and CT. In conclusion, our study shows that the subcutaneous and intraperitoneal injection of HA associated with adipose-derived stromal cells (ASCs) is safe. The association of HA and ASCs did not induce local or systemic toxicity. Thus, the administration of volume equal to or less than 0.2 mL of the agent filler (1×106 ASC+HA 1%) should be considered for subsequent studies and may be an alternative to dermal fillers due to the expected lasting effects