
Fernando Figueroa- MD
- Head at Universidad de los Andes (Santiago de Chile)
Fernando Figueroa
- MD
- Head at Universidad de los Andes (Santiago de Chile)
About
87
Publications
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Introduction
Current research is in Stem cell biology, Cell therapy in autoimmune and degenerative diseases. Metabolic control of Mesenchymal Stromal Cell function
Current institution
Universidad de los Andes (Santiago de Chile)
Current position
- Head
Publications
Publications (87)
Mesenchymal stem cells (MSCs) have fueled ample translation for the treatment of immune-mediated diseases. They exert immunoregulatory and tissue-restoring effects. MSC-mediated transfer of mitochondria (MitoT) has been demonstrated to rescue target organs from tissue damage, yet the mechanism remains to be fully resolved. Therefore, we explored th...
Rigorous testing of cell therapies in South America struggles with emerging opportunities and regulatory deficiencies. As in other continents, these tend to be permissive with commercial opportunism but stifling for research. We describe a successful biotechnological entrepreneurship, born from within an academic institution, to foster science and...
Knee osteoarthritis (OA) is a leading cause of pain and disability. Although conventional treatments show modest benefits, pilot and phase I/II trials with bone marrow (BM) and adipose‐derived (AD) mesenchymal stromal cells (MSCs) point to the feasibility, safety, and occurrence of clinical and structural improvement in focal or diffuse disease. Th...
Rationale:
Umbilical cord-derived mesenchymal stem cells (UC-MSC) are easily accessible and expanded in vitro, possess distinct properties, and improve myocardial remodeling and function in experimental models of cardiovascular disease. Although bone marrow-derived mesenchymal stem cells have been previously assessed for their therapeutic potentia...
Severe respiratory consequences of the COVID-19 pandemic have prompted urgent need for novel therapies. Cell-based approaches, primarily using mesenchymal stem (stromal) cells (MSCs), have demonstrated safety and possible efficacy in patients with the acute respiratory distress syndrome (ARDS), although not as yet well studied in respiratory virus-...
Objective
The inflammatory responses from synovial fibroblasts and macrophages and the mitochondrial dysfunction in chondrocytes lead to oxidative stress, disrupt extracellular matrix (ECM) homeostasis, and accelerate the deterioration process of articular cartilage in osteoarthritis (OA). In recent years, it has been proposed that mesenchymal stro...
Osteoarthrosis (OA) is a leading cause of disability and early mortality, with no disease modifying treatment. Mitochondrial (MT) dysfunction and changes in energy metabolism, leading to oxidative stress and apoptosis, are main drivers of disease. In reaction to stress, mesenchymal stromal/stem cells (MSCs) donate their MT to damaged tissues.
Metho...
Osteoarthritis (OA) is an increasingly frequent chronic condition leading to global disability. Our group has evidenced the effectiveness of Mesenchymal Stem Cells (MSC) in OA. MSC are known to transfer their mitochondria (MitoT) to damaged cells, conveying restorative effects. Of interest, 30% of dysfunctional proteins in human OA cartilage are of...
Background & Aim
Osteoarthritis (OA) is the most frequent joint disease worldwide with yet no known disease modifying drugs. In OA chondrocytes (OAC), the dysregulation of the metabolic biosensors that control mitochondrial biogenesis accounts for decreased numbers of mitochondria (MT) and reduced ATP levels in OA. Recently, our group evidenced tha...
Background:
Chronic kidney disease (CKD) is a growing public health concern, and available treatments are insufficient in limiting disease progression. New strategies, including regenerative cell-based therapies, have emerged as therapeutic alternatives. Results from several groups, including our own, have reported evidence of a supportive role fo...
Background & Aim
The immunoregulatory and tissue restoring effects of Mesenchymal stem cells (MSCs) are mediated by the production of bioactive paracrine factors. While soluble proteins and extracellular vesicles are the main contributory, evidence suggests that mitochondrial transfer from MSCs (MitoT) may also play a significant role. In actual fa...
The therapeutic effect of mesenchymal stem cells (MSCs) in multiple sclerosis (MS) and the experimental autoimmune encephalomyelitis (EAE) model has been well described. This effect is, in part, mediated through the inhibition of IL17-producing cells and the generation of regulatory T cells. While proinflammatory cytokines such as IFNγ, TNFα, and I...
IL17 mesenchymal stem cells (MSCs) pretreatment increases MSCs therapeutic potential in experimental autoimmune encephalomyelitis (EAE). (A) Daily evaluation of clinical score was performed from the day of MSCs administration until euthanasia. (B) The area under the curve (AUC) of the clinical score for each treatment was calculated and compared. L...
Phenotypic characterization and differentiation potential of wild-type (WT) and L17RA−/− mesenchymal stem cells (MSCs). (A) WT and IL17RA−/− MSCs were stained with specific antibodies against CD45, CD34, CD29, CD44, and Sca-1 and analyzed by flow cytometry. Histograms are representative of at least three independent experiments. (B) Differentiation...
Since they were first described, mesenchymal stem cells (MSCs) have been shown to have important effector mechanisms and the potential for use in cell therapy. A great deal of research has been focused on unveiling how MSCs contribute to anti-inflammatory responses, including describing several cell populations involved and identifying soluble and...
Mesenchymal stem cells (MSCs) are multipotent stem cells that are able to immunomodulate cells from both the innate and the adaptive immune systems promoting an anti-inflammatory environment. During the last decade, MSCs have been intensively studied in vitro and in vivo in experimental animal model of autoimmune and inflammatory disorders. Based o...
Background
Recently, it has been observed that mesenchymal stem cells (MSCs) can modulate their immunoregulatory properties depending on the specific in-vitro activation of different Toll-like receptors (TLR), such as TLR3 and TLR4. In the present study, we evaluated the effect of polyinosinic:polycytidylic acid (poly(I:C)) and lipopolysaccharide (...
The neurotransmitter GABA has been recently identified as a potent immunosuppressive agent that targets both innate and adaptive immune systems and prevents disease progression of several autoimmunity models. Mesenchymal stem cells (MSCs) are self-renewing progenitor cells that differentiate into various cell types under specific conditions, includ...
Background aims:
Immunomodulatory properties of human umbilical cord-derived mesenchymal stromal cells (UCMSCs) can be differentially modulated by toll-like receptors (TLR) agonists. Here, the therapeutic efficacy of short TLR3 and TLR4 pre-conditioning of UCMSCs was evaluated in a dextran sulfate sodium (DSS)-induced colitis in mice. The novelty...
Recently, a non-invasive and highly proliferative stem cell population from menstrual blood called MenSCs has been identified. Despite their use in clinical studies, their immunomodulatory properties have not yet been investigated. In this context, we studied the immunosuppressive properties of MenSCs in comparison with the well-characterized bone...
Introduction:
Sepsis is a clinical syndrome associated with a severe systemic inflammation induced by infection. Although different anti-microbial drugs have been used as treatments, morbidity and mortality rates remain high. Mesenchymal stem cells (MSCs) derived from the bone marrow have demonstrated a partial protective effect in sepsis. Menstru...
Significance:
This study analyzed the biological characteristics of mesenchymal stem cells (MSCs) isolated from fetal and maternal placental origins. The findings can be summarized as follows: (a) important differences were found in the expression of CD56; (b) a different mesodermal differentiation potential was found in favor of fetal MSCs; (c) a...
MicroRNAs control the differentiation and function of B cells, which are considered key elements in the pathogenesis of systemic lupus erythematosus (SLE). However, a common micro(mi)RNA signature has not emerged since published data includes patients of variable ethnic background, type of disease, and organ involvement, as well as heterogeneous ce...
Background:
Intracoronary delivery of autologous bone marrow mononuclear cells is an interesting therapeutic promise for patients with heart failure of different etiologies.
Aim:
To evaluate the long-term safety and efficacy of this therapy in patients with dilated cardiomyopathy of different etiologies under optimal medical treatment.
Patients...
Stem cells isolated from menstrual fluid (MenSCs) exhibit mesenchymal stem cell (MSCs)-like properties including multi-lineage differentiation capacity. Besides, menstrual fluid has important advantages over other sources for the isolation of MSCs, including ease of access and repeated sampling in a noninvasive manner. Such attributes allow the rap...
Supplementary figure 1: Correlation of Th1, Th17 and Treg analysis by flow cytometry and RT-qPCR.
Background and objectives Several microRNAs are known to control the differentiation and function of B cells, that are considered key elements in the pathogenesis of systemic lupus erythematosus (SLE). However, a common miRNA signature has not emerged in SLE, since published data includes patients of variable ethnic background, type of disease and...
The Silences of the Archives, the Reknown of the Story.
The Martin Guerre affair has been told many times since Jean de Coras and Guillaume Lesueur published their stories in 1561. It is in many ways a perfect intrigue with uncanny resemblance, persuasive deception and a surprizing end when the two Martin stood face to face, memory to memory, befor...
Background: Intracoronary delivery of autologous bone marrow mononuclear cells is an interesting therapeutic promise for patients with heart failure of different etiologies. Aim: To evaluate the long-term safety and efficacy of this therapy in patients with dilated cardiomyopathy of different etiologies under optimal medical treatment. Patients and...
Available medical therapy is unable to completely prevent or revert the pathological cardiac remodeling secondary to ischemia or other injuries, which is responsible for the development of heart failure. Regenerative medicine through stem cells had an explosive development in the cardiovascular area during the past decade. Stem cells possess the ca...
Menstrual-derived stem cells (MenSCs) are a new source of mesenchymal stem cells isolated from the menstrual fluid. Currently, there is a growing interest in their clinical potential due to fact that they are multipotent, highly proliferative, and easy to obtain in a non-invasive manner. Sampling can be repeated periodically in a simplified and rep...
Introduction:
Patients with systemic lupus erythematosus (SLE) are at increased risk for premature death, particularly among young adults, and present dilemmas regarding drug efficacy versus toxicity. Novel therapeutic strategies have included the use of mesenchymal stem cell (MSC) therapies that are promising but still have limitations. In severa...
Adaptive immune response has been implicated in inflammation and fibrosis as a result of exposure to mineralocorticoids and a high-salt diet. We hypothesized that in mineralocorticoid-salt-induced hypertension, activation of the mineralocorticoid receptor alters the T-helper 17 lymphocyte (Th17)/regulatory T-lymphocyte/interleukin-17 (IL-17) pathwa...
Introduction
Mesenchymal stem cells (MSCs) are adult, multipotent, stem cells with immunomodulatory properties. The mechanisms involved in the capacity of MSCs to inhibit the proliferation of proinflammatory T lymphocytes, which appear responsible for causing autoimmune disease, have yet to be fully elucidated. One of the underlying mechanisms stud...
Background: Recent studies indicate that intra-coronary delivery of autologous bone marrow mono-nuclear cells (BMCs) improves the ejection fraction (LVEF) and other clinical markers in patients with heart failure (HF). Aim: To evaluate the safety and efficacy of intraco-ronary delivery of autologous BMCs in patients with HF in dilated phase under o...
The therapeutic approaches for chronic kidney disease (CKD) have been able to reduce proteinuria, but not diminish the disease progression. We have demonstrated beneficial effects by injection of bone marrow derived mesenchymal stem cells (BM-MSCs) from healthy donors in a rat model of CKD. However, it has recently been reported that BM-MSCs derive...
The therapeutic approaches for chronic kidney disease (CKD) have been able to reduce proteinuria, but not diminish the disease progression. We have demonstrated beneficial effects by injection of bone marrow derived mesenchymal stem cells (BM-MSCs) from healthy donors in a rat model of CKD. However, it has recently been reported that BM-MSCs derive...
Th17 cells, a recently described subtype of CD4+ effector lymphocytes, have been linked to cell-mediated autoimmune and inflammatory diseases as well as to cardiovascular diseases. However, the participation of IL-17A in myocardial ischemic injury has not been clearly defined. We therefore conducted the present study to evaluate IL-17A and Th17-rel...
Aim(s):
To explore the relationship between biomarkers of systemic inflammation in plasma and gingival crevicular fluid in early pregnancy and the subsequent development of pre-eclampsia in patients with periodontitis.
Materials and methods:
A case-control study was performed. From a cohort composed of 126 pregnant women, 43 normotensive healthy...
MSC display potent suppressive properties initially described a decade ago. More recently, MSC suppressive activities on T-cell effector pathways have been investigated. MSC modulate CD4 differentiation through different mechanisms depending on culture conditions and display disparate activities on T cells according to their differentiation status....
Mesenchymal stem cells (MSCs) are now known to display not only stem cell multipotency, but also robust antiinflammatory and regenerative properties. After widespread in-vitro and in-vivo preclinical testing, autologous and allogeneic MSCs have been applied in a range of immune mediated conditions, including graft versus host disease, Crohn's disea...
Th17 cells, a recently described subtype of CD4+ effector lymphocytes, have been linked to cell-mediated autoimmune and inflammatory diseases as well as to cardiovascular diseases. However, the participation of IL-17A in myocardial ischemic injury has not been clearly defined. We therefore conducted the present study to evaluate IL-17A and Th17-rel...
Mesenchymal stem cells (MSCs) are now known to display not only stem cell multipotency, but also robust antiinflammatory and regenerative properties. After widespread in-vitro and in-vivo preclinical testing, autologous and allogeneic MSCs have been applied in a range of immune mediated conditions, including graft versus host disease, Crohn's disea...
CKD (chronic kidney disease) has become a public health problem. The therapeutic approaches have been able to reduce proteinuria, but have not been successful in limiting disease progression. In this setting, cell therapies associated with regenerative effects are attracting increasing interest. We evaluated the effect of MSC (mesenchymal stem cell...
Mesenchymal stem cells (MSCs) are now known to display not only adult stem cell multipotency but also robust anti-inflammatory and regenerative properties. After widespread in vitro and in vivo preclinical testing in several autoimmune disease models, allogenic MSCs have been successfully applied in patients with severe treatment-refractory systemi...
Mesenchymal stem cells (MSCs) are multipotent progenitors with broad immunosuppressive properties. However, their therapeutic use in autoimmune disease models has shown dissimilar effects when applied at different stages of disease. We therefore investigated the effect of the addition of MSCs on the differentiation of Th1, Treg and Th17 cells in vi...
Mesenchymal stem cells (MSCs) exert suppressive effects in several disease models including lupus prone mice. However, autologous MSC therapy has not been tested in human systemic lupus erythematosus (SLE). We evaluate the safety and efficacy of bone marrow (BM)-derived MSCs in two SLE patients; the suppressor effect of these cells in-vitro and the...
Excessive production of aldosterone leads to the development of hypertension and cardiovascular disease by generating an inflammatory state that can be promoted by T cell immunity. Because nature and intensity of T cell responses is controlled by dendritic cells (DCs), it is important to evaluate whether the function of these cells can be modulated...
Despite the availability of newer therapeutic interventions to improve clinical outcome in patients with Systemic Lupus Erythematosus (SLE), the incidence of infections as a cause of morbidity and mortality has not changed over the past 30 years. SLE itself increases the risk of infection, due to genetic (complement deficiencies) and acquired facto...
Diabetes mellitus is an important risk factor for cardiovascular complications among patients on hemodialysis. However, the incidence of these complications among non diabetic patients on hemodialysis is not well known.
To assess the incidence of cardiovascular complications in non diabetic patients on hemodialysis. Patients and methods: Seventy fi...
Background: Diabetes mellitus is an important risk factor for cardiovascular complications among patients on hemodialysis. However, the incidence of these complications among non diabetic patients on hemodialysis is not well known. Aim: To assess the incidence of cardiovascular complications in non diabetic patients on hemodialysis. Patients and me...
Rheumatic heart disease (RHD) is a delayed consequence of a pharyngeal infection with Group A streptococcus (GAS), usually ascribed to a cross-reactive immune response to the host cardiac tissues. Acute rheumatic fever (ARF) and its ensuing valvular sequelae are thus considered the prototype of a post-infectious autoimmune disease, with no direct e...
Background: Rheumatic heart disease (RHD) is a delayed consequence of a pharyngeal infection with Group A streptococcus (GAS), usually ascribed to a cross-reactive immune response to the host cardiac tissues. Acute rheumatic fever (ARF) and its ensuing valvular sequelae are thus considered the prototype of a post-infectious autoimmune disease, with...
To examine whether self-assessment of tender and swollen joints by patients with rheumatoid arthritis (RA) can be used to evaluate changes in disease activity instead of joint counts by physicians.
Eighty-two patients with RA taking part in controlled studies were recruited for investigation. The patient's self-assessment of joint tenderness and sw...
Acute rheumatic fever (ARF) and its chronic valvular sequelae are the delayed consequence of a pharyngeal infection with group A Streptococcus (GAS). Several GAS proteins have been shown to be superantigens, raising the possibility that the expansion or deletion of T cells expressing specific Vbeta regions might play a role in the pathogenesis of A...
Polymorphisms of Fc receptors for IgG (Fc gamma R) have been proposed as a genetic factor that influences susceptibility for systemic lupus erythematosus (SLE). Human Fc gamma RIIa has 2 codominantly expressed alleles, H131 and R131, which differ at amino acid position 131 in the second extracellular domain (histidine or arginine respectively) and...
Rheumatic Heart Disease (RHD) is a delayed consequence of a pharyngeal infection with group A streptococcus (GAS), usually ascribed to a cross-reactive immune response to the host's cardiac tissues. Several GAS proteins have been reported to be superantigens, also raising the possibility that T cells in RHD could be driven by superantigens. We ther...
Background: Polymorphisms of Fc receptors for IgG (FcgR) have been proposed as a genetic factor that influences susceptibility for systemic lupus erythematosus (SLE). Human FcgRIIa has 2 codominantly expressed alleles, H131 and R131, which differ at amino acid position 131 in the second extracelular domain (histidine or arginine respectively) and d...
Eosinophilic fasciitis (EF) is a scleroderma-like disease of unknown etiology characterized by cutaneous swelling and induration that affects predominantly the extremities, elevated immune globulins, and peripheral eosinophilia. We report three patients with clinical, laboratory and pathologic characteristics of EF. The main symptoms were cutaneous...
To determine the frequency of occurrence and long term evolution of subclinical carditis in patients with acute rheumatic fever.
Valvar incompetence was detected by clinical examination and Doppler echocardiographic imaging during the acute and quiescent phases of rheumatic fever. Patients were followed prospectively and submitted to repeat examina...
OBJECTIVE
To determine the frequency of occurrence and long term evolution of subclinical carditis in patients with acute rheumatic fever.
DESIGN
Valvar incompetence was detected by clinical examination and Doppler echocardiographic imaging during the acute and quiescent phases of rheumatic fever. Patients were followed prospectively and submitted...
During the last few decades, basic scientists and clinicians have gained a deeper insight of the cellular and molecular physiology of the immune system. The widespread application of molecular biology and genetic techniques has advanced our understanding of states of health and disease, bringing forth renewed hopes concerning the advent of a more "...
During the last few decades, basic scientists and clinicians have gained a deeper insight of the cellular and molecular physiology of the immune system. The widespread application of molecular biology and genetic techniques has advanced our understanding of states of health and disease, bringing forth renewed hopes concerning the advent of a more "...
Neuroendocrine factors play an important role in the expression of autoimmune diseases. Prolactin (PRL) can induce T-cell proliferation and macrophage activation. Elevated PRL levels have been described in patients with rheumatoid arthritis (RA).
We studied immunological and clinical effects of PRL suppression in 9 RA patients with active disease,...
The association of primary adrenal insufficiency with antiphospholipid antibodies is usually reported in the context of adrenal thrombosis or hemorrhage. We describe a 35-year-old woman who developed a primary antiphospholipid syndrome (spontaneous abortion, thrombocytopenia, and cerebrovascular occlusion) in association with primary adrenal insuff...
Cyclosporine may be useful in the treatment of rheumatoid arthritis refractory to other immunosuppressive agents, in doses of less than 10 mg/kg/day to minimize its nephrotoxic potential, that is enhanced with prolonged use or concomitant administration of anti-inflammatory drugs. We report 15 patients aged 50 +/- 12 years with erosive rheumatoid a...
Prolactin markedly influences cellular and humoral immunity in animals, but there is little information on its role in men. The aim of this work was to study the immune effects of pharmacological modification of prolactin levels in 5 healthy individuals. Peripheral blood mononuclear cell proliferative response to mitogens and antigens, interleukin-...
Recent reports describe the association of antiphospholipid antibodies (aPL) with chorea or severe heart valve lesions in systemic lupus erythematosus, lupus-like disease, or the primary antiphospholipid antibody syndrome. We conducted a case series and a case-control investigation of patients with rheumatic fever with Sydenham chorea or other mani...
Recently, the association between anti-phospholipid antibodies (false positive VDRL, lupus anticoagulant or anti-cardiolipin antibody) and diverse clinical manifestations has been termed antiphospholipid syndrome. We report 6 female patients with "primary" antiphospholipid syndrome, not related to connective tissue disorders. Their age ranged from...
In this review of 159 pts with systemic lupus erythematosus (SLE) followed for 18 years, 78 pts had major infections (20/100 pt-years). Patients with infection had a higher incidence of proteinuria, central nervous system involvement, the use of methylprednisolone boluses and mortality rate. Infection was independent of the amount of steroids and i...
We report 3 patients with congenital A-V block whose mothers had anti-Ro or anti-La antibodies. One of them had systemic lupus with serum anti-Ro antibodies; the other had anti-Ro antibodies and no clinical manifestations; the third had an undifferentiated connective tissue disorder with anti-La antibodies in the serum. The epidemiology of this ass...