Katherine Carvalho - Academia.edu (original) (raw)

Papers by Katherine Carvalho

The International Journal of Artificial Organs, 2008

Objectives Cell transplantation is considered a novel approach in the treatment of myocardiopathy... more Objectives Cell transplantation is considered a novel approach in the treatment of myocardiopathy. The objective of this study was to evaluate the effects of autologous mononuclear stem cell therapy in doxorubicin-induced dilated myocardiopathy by conducting both functional and histopathologic analysis. Methods Seventy male rats were doxorubicin injected intraperitoneally for 2 weeks. At 1 month, the animals that had demonstrated left ventricular ejection fractions less than 40% were randomly divided into a mononuclear stem cell group and controls. Mononuclear stem cells were isolated. All animals underwent echocardiographic study: baseline, pre-cell therapy, and at 1 month post-cell therapy, and analyzed by the nonparametric Mann-Whitney test. Transplants were performed by subepicardial injections. Standard staining was performed. Results Twenty-three animals were randomly treated: mononuclear stem cell and control groups, with 11 rats completing the study. Cell viability was 85%. ...

Current Eye Research, 2021

ABSTRACT Purpose This study aimed to evaluate a cell therapy strategy with human neural precursor... more ABSTRACT Purpose This study aimed to evaluate a cell therapy strategy with human neural precursor cells (hNPCs) to treat diabetic retinopathy (DR) in Wistar rats induced to diabetes by injecting streptozotocin. Material and Methods The Wharton’s jelly mesenchymal stem cells (WJ-MSCs) were isolated, expanded, and seeded onto a biopolymer substrate to develop neurospheres and obtain the hNPCs. The animals were divided into three groups: non-diabetic (ND) n = four, diabetic without treatment (DM) n = nine, and diabetic with cell therapy (DM + hNPCs) n = nine. After 8 weeks of diabetes induction and DR characteristics installed, intravitreal injection of hNPCs (1 × 106 cell/µL) was performed in the DM + hNPCs group. Optical Coherence Tomography (OCT) and Electroretinography (ERG) evaluations were conducted before and during diabetes and after cell therapy. Four weeks posttreatment, histopathological and immunohistochemistry analyses were performed. Results The repair of the retinal structures in the treated group (DM + hNPCs) was observed by increased thickness of neuroretinal layers, especially in the ganglion cell and photoreceptor layers, higher ERG oscillatory potentials (OPs) amplitudes, and transplanted hNPCs integration into the Retinal Pigment Epithelium. Conclusions The results indicate that hNPCs reduced DR progression by a neuroprotective effect and promoted retinal repair, making them potential candidates for regenerating the neuroretinal tissue.

Journal of Functional Biomaterials

To investigate the effect of transplantation of stem cells from the bone marrow mononuclear cells... more To investigate the effect of transplantation of stem cells from the bone marrow mononuclear cells (BMMC) associated with 15d-PGJ2-loaded nanoparticles in a rat model of chronic MI. Chronic myocardial infarction (MI) was induced by the ligation of the left anterior descending artery in 40 male Wistar rats. After surgery, we transplanted bone marrow associated with 15d-PGJ2-loaded nanoparticle by intramyocardial injection (106 cells/per injection) seven days post-MI. Myocardial infarction was confirmed by echocardiography, and histological analyses of infarct morphology, gap junctions, and angiogenesis were obtained. Our results from immunohistochemical analyses demonstrated the presence of angiogenesis identified in the transplanted region and that there was significant expression of connexin-43 gap junctions, showing a more effective electrical and mechanical integration of the host myocardium. This study suggests that the application of nanoparticle technology in the prevention and...

This study aimed to evaluate cell therapy with human neural precursor cells (hNPCs) in 29 diabeti... more This study aimed to evaluate cell therapy with human neural precursor cells (hNPCs) in 29 diabetic retinopathy (DR) Wistar rats, induced to diabetes by intraperitoneal injection with strep30 tozotocin. Wharton's Jelly Mesenchymal stem cells (WJ-MSCs) were isolated, expanded, and 31 seeded onto a biopolymer substrate without growth factors to develop neurospheres to obtain the 32 hNPCs, characterized by immunocytochemistry. The animals were divided into three groups; 33 non-diabetic (ND) n = four; diabetic without treatment (DM) n = nine; and diabetic with cell ther34 apy (DM + hNPCs) n = nine. After eight weeks of diabetes induction and verified DR, intravitreal 35 injection of hNPCs (1 x 106 cel/μL) was performed in the DM + hNPCs group. Optical Coherence 36 Tomography (OCT) and Electroretinography (ERG) evaluations were done before and after dia37 betes induction and after cell therapy. Eye enucleation occurred four weeks after treatment for the 38 histopathological and immuno...

Biological scaffolds have become an attractive approach for repairing the infarcted myocardium an... more Biological scaffolds have become an attractive approach for repairing the infarcted myocardium and have been shown to facilitate constructive remodeling in injured tissues. This study aimed to investigate the possible utilization of bacterial cellulose (BC) membrane patches containing cocultured cells to limit myocardial postinfarction pathology. Myocardial infarction (MI) was induced by ligating the left anterior descending coronary artery in 45 Wistar rats, and patches with or without cells were attached to the hearts. After one week, the animals underwent echocardiography to assess for ejection fraction and left ventricular end-diastolic and end-systolic volumes. Following patch formation, the cocultured cells retained viability of >90% over 14 days in culture. The patch was applied to the myocardial surface of the infarcted area after staying 14 days in culture. Interestingly, the BC membrane without cellular treatment showed higher preservation of cardiac dimensions; however...

Arquivos brasileiros de cardiologia, Apr 12, 2018

Physical exercise should be part of the treatment of post-acute myocardial infarction (AMI) patie... more Physical exercise should be part of the treatment of post-acute myocardial infarction (AMI) patients. To evaluate the effects of two training prescription models (continuous x interval) and its impact on ventricular function in rats after AMI with normal ventricular function. Forty Wistar rats were evaluated by echocardiography 21 days after the AMI. Those with LVEF = 50% (n = 29) were included in the study and randomized to control group (CG n = 10), continuous training group (CTG n = 9) or interval training group (ITG, n = 10). Then, a swimming test with control of lactate production was performed. Based on its result, the lactate threshold (LT) was established to define the training intensities. After six weeks, the animals were reassessed by echocardiography and lactate production. Outcome measures were end-diastolic diameter (EDD), end-systolic diameter (ESD), left ventricular ejection fraction (LVEF, %) lactate at rest, lactate without overload, and lactate with 12g and 13.5g ...

Stem cell research & therapy, Feb 26, 2018

In the past years, cardiac mortality has decreased, but cardiac diseases are still responsible fo... more In the past years, cardiac mortality has decreased, but cardiac diseases are still responsible for millions of deaths every year worldwide. Bone-marrow mesenchymal stem cells (BMSCs) transplantation may be a promising therapeutic strategy because of its capacity to differentiate into cardiac cells. Current research indicates that chemical substances, microRNAs, and cytokines have biological functions that regulate the cardiomyocytes differentiation of BMSCs. In this review, we chiefly summarize the regulatory factors that induce BMSCs to differentiate into cardiomyocytes.

International journal of molecular sciences, Jan 19, 2017

Bone marrow-derived stem cells (BMDSCs) play an essential role in organ repair and regeneration. ... more Bone marrow-derived stem cells (BMDSCs) play an essential role in organ repair and regeneration. The molecular mechanisms by which hormones control BMDSCs proliferation and differentiation are unclear. Our aim in this study was to investigate how a lack of ovarian or/and thyroid hormones affects stem cell number in bone marrow lineage. To examine the effect of thyroid or/and ovarian hormones on the proliferative activity of BMDSCs, we removed the thyroid or/and the ovaries of adult female rats. An absence of ovarian and thyroid hormones was confirmed by Pap staining and Thyroid Stimulating Hormone (TSH) measurement, respectively. To obtain the stem cells from the bone marrow, we punctured the iliac crest, and aspirated and isolated cells by using a density gradient. Specific markers were used by cytometry to identify the different BMDSCs types: endothelial progenitor cells (EPCs), precursor B cells/pro-B cells, and mesenchymal stem cells (MSCs). Interestingly, our results showed tha...

Journal of Tissue Engineering and Regenerative Medicine

Surgical correction of tracheal stenosis is still a complex and challenging procedure. Acellular ... more Surgical correction of tracheal stenosis is still a complex and challenging procedure. Acellular human amniotic membranes (AHAM) represent a promising biomaterial source for tissue regeneration. The aim of this study was to evaluate whether AHAM grafts improve tissue regeneration of the trachea in a rabbit model of tracheostomy. Twenty rabbits were randomized into two groups. Animals in the control group underwent surgical tracheostomy only and animals in the AHAM group underwent surgical tracheostomy and received an AHAM graft that covered the defect site. We examined tissues at the site of tracheostomy 60 days after surgery by histological analysis with hematoxylin and eosin (H&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;E), Movat&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s pentachrome stain and immunohistochemistryby analysis with anti-aggrecan antibodies. The average perimeter and area of the defect 60 days after surgery were smaller in animals in the control group than in the AHAM group (P = 0.011 and P = 0.011, respectively). Histological analysis of AHAM group revealed neovascularization, islands of immature cartilage, pseudostratified ciliated epithelium and connective tissue at the site of AHAM engraftment, whereas only pseudostratified ciliated epithelium and connective tissue were observed at the defect site in tissues of animals in the control group. Regeneration of islands of immature cartilage tissue with hyaline pattern and pseudostratified ciliated epithelium were confirmed by immunohistochemistryanalysis. These results indicate that AHAM engraftment could facilitate neovascularization and regeneration of immature cartilage in a model of tracheal injury. It&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s use may lower the risk of postoperative complications including stenosis of trachea.

Apoptosis, 2015

Cardiovascular diseases are major causes of mortality and morbidity. Death of cardiac cells disru... more Cardiovascular diseases are major causes of mortality and morbidity. Death of cardiac cells disrupts cardiac function and leads to increased mortality and morbidity among cardiovascular patients. Delineating the regulatory signaling pathways that orchestrate cell survival in the heart has significant therapeutic implications. Cardiac tissue has limited capacity to regenerate and repair. Stem cell therapy is a successful approach for repairing and regenerating ischemic cardiac tissue; however, transplanted cells display very high death percentage, a problem that affects success of tissue regeneration. Thus, stem cell death in the heart represents a major challenge for ongoing research aiming to improve the function of the diseased heart. A number of therapeutic trials on overcoming cardiomyocyte cell death were conducted, however ensuring stem cell survival is not fully understood. Stem cells display multipotency or pluripotency and undergo self renewal, however these events are negatively influenced by upregulation of cell death machinery that accompany the significant decrease in survival and differentiation signals upon cardiovascular injury. While efforts to identify cell types and molecular pathways that promote cardiac tissue regeneration have been productive, studies that focus on blocking the extensive cell death after transplantation are limited. The control of cell death includes multiple networks rather than one crucial pathway, which underlies the challenge of identifying the interaction between various cellular and biochemical components. This review is aimed at exploiting the molecular mechanisms by which stem cells respond to death signals to develop into mature and healthy cardiac cells. Specifically, we focus on a number of factors that control death and survival of stem cells upon transplantation and ultimately contribute to cardiac regeneration. Stem cell resources and selection Both embryonic and adult stem cell types have been applied to improve regeneration and function of the injured heart (30). Various sources of stem cells have been considered for cardiac repair; these include skeletal muscle myoblasts, peripheral blood-derived progenitor cells, bone marrow mononuclear cells, autologous cultured bone marrow cells, adipose-derived stem cells, umbilical/placental/endometrial stem cells, MSCs, cardiac stem cells, embryonic and induced pluripotent stem cells (13, 31-34). Carvalho and co-workers have recently proposed the use of amniotic membrane as a potential source of MSCs that could efficiently boost cardiac tissue regeneration (35). A number of lessons have been learned regarding cell type selection and application of cell therapy. Initial studies were first focused on ESCs, then researchers used autologous adult stem cells which possess almost the same features like ESCs beside the advantage that autologous tissue is always better accepted by immune system than any xenograft (36). On the other hand, cells participating in the repair process are suggested to be host cells that are naturally chemo-attracted to the injury site, through occasional host neo-angiogenesis, and are not delivered to the damaged area directly by transplantation (37). Selection of stem cells is often based on certain criteria such as cell survival and proper metabolic activity as found in MSCS when transplanted into ischemic conditions (Mylotte et al., 2008). Therefore, a large number of studies have recently suggested that cell therapy with bone marrow MSCs has great promises in regenerating and repopulating the damaged myocardium, restoring its function and is a safe effective strategy for treating ischemic heart failure (38-40). Bone marrow-derived MSCs were frequently used to regenerate cardiac ischemic tissues of various animal and human models (41-48). An advantageous aspect of autologous MSCs is that they can be easily obtained from adult patients, they are less likely to cause immune problems like ESC (36) and they can differentiate into functional cardiomyocytes, however poor cell adhesion and increased apoptosis decrease their engraftment (12, 49, 50). Thus, enhancement of cell survival is essential to help better selection of stem cell and to maximize the benefits of cell therapy for heart diseases. With a better clarification of the factors that decide which stem cells live or die we would likely select only the best stem cells that are the healthiest to use.

Objectives: Doppler Echocardiography has been shown to reflect thyroid hormone action in primary ... more Objectives: Doppler Echocardiography has been shown to reflect thyroid hormone action in primary thyroid dysfunction. The aim of the present study was to evaluate the cardiac function after total thyroidectomy in old rats using echocardiographic measures. Methods: Female Wistar rats aged 24 months old (referred to as adult) were divided into 2 groups with 15 animals each: Euthyroid (Eut) and Hypothyroid (Hypo) rats. Hypothyroidism was induced by total thyroidectomy. The plasmatic levels of T 3 , T 4 , TSH and free ionic calcium were measured. Echocardiographic analysis was performed using the following parameters: left ventricular end-diastolic (LVED) left ventricular end-systolic (LVES), ejection fraction (EF) and Tei index. Results: In both groups, the LVES ranged from 0.2 to 0.5 p <0.048 and the EF from 50.3 to 45.2 p<0.030.There was not statistically significant difference in HR, LVED and Tei-index values. It was observed decrease in T 3 levels (72.0 to 30.4 µg/dl, p<0.001) and T 4 levels (3.1 to 0.4 µg/dl, p<0.001) and increase in TSH levels (1.6 to 40.7 mU/mol, p<0.001) in Hypo group. The free ionic calcium levels increased from 0.1 to 0.9 mmol/L (p<0.001) in Hypo group. Conclusion: It was identified a reduction of cardiac function in old animals with hypothyroidism using Doppler-Echocardiography measures. These results indicated that hypothyroidism is associated with impairment in cardiac function in old patients and that Doppler echocardiography, is a useful and noninvasive tool for the diagnosis of cardiac dysfunction induced by this thyroid disorder.

Stem cells international, 2015

Transplantation proceedings

Muscle healing is a time-dependent process associated with an increase in the total amount of loc... more Muscle healing is a time-dependent process associated with an increase in the total amount of local collagen fibers. Platelet-rich plasma therapy (PRPT) associated with exercise may improve this healing process. The aim of this study was to demonstrate the regenerative effect of PRPT in association with exercise training on musculoskeletal healing. Male Wistar rats were submitted to an injury in the vastus lateralis muscle and randomly divided into 4 groups (n = 5/group): sedentary sham-operated (SSO); sedentary group submitted to PRPT (SPR); swim-trained (SWT); and swim-trained group submitted to PRPT (SWP). Serum lactate level was used to confirm the training protocol effectiveness to increase aerobic fitness. The collagen fiber concentration was measured by the polarization colors in picrosirius red-stained tissue sections. Lactate levels decreased in both training groups (SWT and SWP; P < .05) after training (SWT: from 6.2 ± 0.44 to 4.7 ± 0.22 mmol/L; SWP: from 5.5 ± 0.99 to ...

World journal of transplantation, Jan 24, 2013

Chagas cardiomyopathy still remains a challenging problem that is responsible for high morbidity ... more Chagas cardiomyopathy still remains a challenging problem that is responsible for high morbidity and mortality in Central and Latin America. Chagas disease disrupts blood microcirculation via various autoimmune mechanisms, causing loss of cardiomyocytes and severe impairment of heart function. Different cell types and delivery approaches in Chagas Disease have been studied in both preclinical models and clinical trials. The main objective of this article is to clarify the reasons why the benefits that have been seen with cell therapy in preclinical models fail to translate to the clinical setting. This can be explained by crucial differences between the cellular types and pathophysiological mechanisms of the disease, as well as the differences between human patients and animal models. We discuss examples that demonstrate how the results from preclinical trials might have overestimated the efficacy of myocardial regeneration therapies. Future research should focus, not only on studyi...

The International journal of artificial organs, 2008

Cell transplantation is considered a novel approach in the treatment of myocardiopathy. The objec... more Cell transplantation is considered a novel approach in the treatment of myocardiopathy. The objective of this study was to evaluate the effects of autologous mononuclear stem cell therapy in doxorubicin-induced dilated myocardiopathy by conducting both functional and histopathologic analysis. Seventy male rats were doxorubicin injected intraperitoneally for 2 weeks. At 1 month, the animals that had demonstrated left ventricular ejection fractions less than 40% were randomly divided into a mononuclear stem cell group and controls. Mononuclear stem cells were isolated. All animals underwent echocardiographic study: baseline, pre-cell therapy, and at 1 month post-cell therapy, and analyzed by the nonparametric Mann-Whitney test. Transplants were performed by subepicardial injections. Standard staining was performed. Twenty-three animals were randomly treated: mononuclear stem cell and control groups, with 11 rats completing the study. Cell viability was 85%. Mononuclear stem cells (n=5...

World Journal of Cardiology, 2011

Although some authors suggest that there is mitotic division in the heart, most cardiomyocytes do... more Although some authors suggest that there is mitotic division in the heart, most cardiomyocytes do not have the capacity to regenerate after myocardial infarction and when this occurs there is a deterioration of contractile function, and if the area of infarction is extensive ventricular remodeling may occur, leading to the development of heart failure. Cell transplantation into the myocardium with the goal of recovery of cardiac function has been extensively studied in recent years. The effects of cell therapy are based directly on the cell type used and the type of cardiac pathology. For myocardial ischemia in the hibernating myocardium, bone marrow cells have functional benefits, however these results in transmural fibrosis are not evident. In these cases there is a benefit of implantation with skeletal myoblasts, for treating the underlying cause of disease, the loss of cell contractility.