OCT4 silencing triggers its epigenetic repression and impairs the osteogenic and adipogenic differentiation of mesenchymal stromal cells

Mechanisms mediating mesenchymal stromal/stem cells’ (MSCs) multipotency are unclear. Although the expression of the pluripotency factor OCT4 has been detected in MSCs, whether it has a functional role in adult stem cells is still controversial. We hypothesized that a physiological expression level of OCT4 is important to regulate MSCs’ multipotency and trigger differentiation in response to environmental signals. Here, we specifically suppressed OCT4 in MSCs by using siRNA technology before directed differentiation. OCT4 expression levels were reduced by 82% in siOCT4-MSCs, compared with controls. Interestingly, siOCT4-MSCs also presented a hypermethylated OCT4 promoter. OCT4 silencing significantly impaired the ability of MSCs to differentiate into osteoblasts. Histologic and macroscopic analysis showed a lower degree of mineralization in siOCT4-MSCs than in controls. Moreover, OCT4 silencing prevented the up-regulation of osteoblast lineage-associated genes during differentiation. Similarly, OCT4 silencing resulted in decreased MSC differentiation potential towards the adipogenic lineage. The accumulation of lipids was reduced 3.0-fold in siOCT4-MSCs, compared with controls. The up-regulation of genes engaged in the early stages of adipogenesis was also suppressed in siOCT4-MSCs. Our findings provide evidence of a functional role for OCT4 in MSCs and indicate that a basal expression of this transcription factor is essential for their multipotent capacity.Fil: Malvicini, Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Santa Cruz, Diego Mario. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Pacienza, Natalia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Yannarelli, Gustavo Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentin

Lentivector Transduction Improves Outcomes Over Transplantation of Human HSCs Alone in NOD/SCID/Fabry Mice

Fabry disease is a lysosomal storage disorder caused by a deficiency of a-galactosidase A (a-gal A) activity that results in progressive globotriaosylceramide (Gb(3)) deposition. We created a fully congenic nonobese diabetic (NOD)/severe combined immunodeficiency (SCID)/Fabry murine line to facilitate the in vivo assessment of human cell-directed therapies for Fabry disease. This pure line was generated after 11 generations of backcrosses and was found, as expected, to have a reduced immune compartment and background a-gal A activity. Next, we transplanted normal human CD34(+) cells transduced with a control (lentiviral vector-enhanced green fluorescent protein (LV-eGFP)) or a therapeutic bicistronic LV (LV-a-gal A/internal ribosome entry site (IRES)/hCD25). While both experimental groups showed similar engraftment levels, only the therapeutic group displayed a significant increase in plasma a-gal A activity. Gb(3) quantification at 12 weeks revealed metabolic correction in the spleen, lung, and liver for both groups. Importantly, only in the therapeutically-transduced cohort was a significant Gb(3) reduction found in the heart and kidney, key target organs for the amelioration of Fabry disease in humans.Fil: Pacienza, Natalia Alejandra. University Health Network; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Yoshimitsu, Makoto. Kagoshima University; Japón. University Health Network; CanadáFil: Mizue, Nobuo. University Health Network; CanadáFil: Au, Bryan C. Y.. University Health Network; CanadáFil: Wang, James C. M.. University Health Network; CanadáFil: Fan, Xin. University Health Network; CanadáFil: Takenaka, Toshihiro. Kagoshima University; JapónFil: Medin, Jeffrey A. University Health Network; Canadá. University of Toronto; Canad

In Vitro Macrophage Assay Predicts the In Vivo Anti-inflammatory Potential of Exosomes from Human Mesenchymal Stromal Cells

Extracellular vesicles (EVs) play key roles in cell biology and may provide new clinical diagnostics and therapies. However, it has proven difficult to develop protocols for their purification and characterization. One of the major barriers in the field has been a lack of convenient assays for their bioactivity. Developing assays has not been a trivial matter, because of the heterogeneity of EVs, the multiple activities they demonstrate, and the uncertainty about their modes of action. Therefore, it is likely that multiple assays for their activities are needed. One important assay will be for the anti-inflammatory activity observed in mice after administration of the small EVs commonly referred to as exosomes. We developed an assay for the anti-inflammatory activity of exosomes with a line of mouse macrophages. The assay makes it possible to rank different preparations of exosomes by their anti-inflammatory activity, and their ranking predicts their efficacy in suppressing LPS-stimulated inflammation in mice. The assay is convenient for comparing multiple samples and, therefore, should be useful in developing protocols for the purification and characterization of anti-inflammatory exosomes.Fil: Pacienza, Natalia Alejandra. Texas A&M University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Lee, Ryang Hwa. Texas A&M University; Estados UnidosFil: Bae, Eun-Hye. Texas A&M University; Estados UnidosFil: Kim, Dong-ki. Texas A&M University; Estados UnidosFil: Liu, Qisong. Texas A&M University; Estados UnidosFil: Prockop, Darwin J.. Texas A&M University; Estados UnidosFil: Yannarelli, Gustavo Gabriel. Texas A&M University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentin

Bone marrow/bone pre-metastatic niche for breast cancer cells colonization: The role of mesenchymal stromal cells

Breast cancer is one of the most common oncological pathologies in women worldwide. While its early diagnosis has considerably improved, about 70 % of advanced patients develop bone metastases with a high mortality rate. Several authors demonstrated that primary breast cancer cells prepare their future metastatic niche –known as the pre-metastatic niche- to turn it into an “optimal soil” for colonization. The role of the different cellular components of the bone marrow/bone niche in bone metastasis has been well described. However, studying the changes that occur in this microenvironment before tumor cells arrival has become a novel research field. Therefore, the purpose of this review is to describe the current knowledge about the modulation of the normal bone marrow/bone niche by the primary breast tumor, in particular, highlighting the role of mesenchymal stem/ stromal cells in transforming this soil into a pre-metastatic niche for breast cancer cells colonization.Fil: Sanmartin, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Borzone, Francisco Raúl. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Giorello, Maria Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Pacienza, Natalia Alejandra. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Yannarelli, Gustavo Gabriel. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Chasseing, Norma Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin

Brief report: The potential role of epigenetics on multipotent cell differentiation capacity of mesenchymal stromal cells

Human umbilical cord perivascular cells (HUCPVCs) are a readily available source of mesenchymal stromal cells (MSCs) for cell therapy. We were interested in understanding how differences from human bone marrow (BM)-derived MSCs might yield insights into MSC biology. We found that HUCPVCs exhibited increased telomerase activity and longer telomeres compared with BM-MSCs. We also observed enhanced expression of the pluripotency factors OCT4, SOX2, and NANOG in HUCPVCs. The methylation of OCT4 and NANOG promoters was similar in both cell types, indicating that differences in the expression of pluripotency factors between the MSCs were not associated with epigenetic changes. MSC methylation at these loci is greater than reported for embryonic stem cells but less than in dermal fibroblasts, suggesting that multipotentiality of MSCs is epigenetically restricted. These results are consistent with the notion that the MSC population (whether BM- or HUCPV-derived) exhibits higher proliferative capacity and contains more progenitor cells than do dermal fibroblasts. © AlphaMed Press.Fil: Yannarelli, Gustavo Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Princess Margaret Hospital; Canadá. Universidad Favaloro; ArgentinaFil: Pacienza, Natalia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University Health Network; Canadá. Universidad Favaloro; ArgentinaFil: Cuniberti, Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro; ArgentinaFil: Medin, Jeffrey. University Health Network; CanadáFil: Davies, John. University of Toronto; CanadáFil: Keating, Armand. Princess Margaret Hospital; Canadá. University of Toronto; Canad

The potential role of epigenetics on multipotent cell differentiation capacity of mesenchymal stromal cells

Human umbilical cord perivascular cells (HUCPVCs) are a readily available source of mesenchymal stromal cells (MSCs) for cell therapy. We were interested in understanding how differences from human bone marrow (BM)-derived MSCs might yield insights into MSC biology. We found that HUCPVCs exhibited increased telomerase activity and longer telomeres compared with BM-MSCs. We also observed enhanced expression of the pluripotency factors OCT4, SOX2, and NANOG in HUCPVCs. The methylation of OCT4 and NANOG promoters was similar in both cell types, indicating that differences in the expression of pluripotency factors between the MSCs were not associated with epigenetic changes. MSC methylation at these loci is greater than reported for embryonic stem cells but less than in dermal fibroblasts, suggesting that multipotentiality of MSCs is epigenetically restricted. These results are consistent with the notion that the MSC population (whether BM- or HUCPV-derived) exhibits higher proliferative capacity and contains more progenitor cells than do dermal fibroblasts.Fil: Yannarelli, Gustavo Gabriel. Universidad Favaloro; Argentina. University Health Network; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pacienza, Natalia Alejandra. University Health Network; Canadá. Universidad Favaloro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cuniberti, Luis Alberto. Universidad Favaloro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Medin, Jeffrey. University Health Network; CanadáFil: Davies, John. University of Toronto; CanadáFil: Keating, Armand. University Health Network; Canadá. University of Toronto; Canad

Human umbilical cord perivascular cells exhibit enhanced cardiomyocyte reprogramming and cardiac function after experimental acute myocardial infarction

We were interested in evaluating the ability of the mesenchymal stromal cell (MSC) population, human umbilical cord perivascular cells (HUCPVCs), to undergo cardiomyocyte reprogramming in an established co-culture system with rat embryonic cardiomyocytes. Results were compared with human bone marrow-derived (BM) MSCs. The transcription factors GATA4 and Mef2c were expressed in HUCPVCs but not BM-MSCs at baseline, and at 7 days increased 7.6 and 3.5-fold respectively, compared with BM-MSCs. Although cardiac-specific gene expression increased in both cell types in co-culture, up-regulation was more significant in HUCPVCs, consistent with Mef2c-GATA4 synergism. Using a lentivector with eGFP transcribed from the a-myosin heavy chain ( a-MHC) promoter, we found that cardiac gene expression was greater in HUCPVCs than BM-MSCs after 14d co-culture (52±17% vs 29±6%, respectively). A higher frequency of HUCPVCs expressed a-MHC protein compared with BM-MSCs (11.6±0.9% vs 5.3±0.3%) however, both cell types retained MSC-associated determinants. We also assessed the ability of the MSC types to mediate cardiac regeneration in a NOD/SCID(gnull) mouse model of acute myocardial infarction (AMI). Fourteen days after AMI, cardiac function was significantly better in celltreated mice compared with control animals and HUCPVCs exhibited greater improvement. Although human cells persisted in the infarct area, the frequency of a-MHC expression was low. Our results indicate that HUCPVCs exhibit a greater degree of cardiomyocyte reprogramming but that differentiation for both cell types is partial. We conclude that HUCPVCs may be preferable to BM-MSCs in the cell therapy of AMI.Fil: Yannarelli, Gustavo Gabriel. University Health Network. Prince Margaret Hospital. Cell Therapy Program; CanadáFil: Dayan, Victor. University Health Network. Prince Margaret Hospital. Cell Therapy Program; CanadáFil: Pacienza, Natalia Alejandra. University Health Network; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lee, Chyan Jang. University Health Network; CanadáFil: Medin, Jeffrey. University Health Network; CanadáFil: Keating, Armand. University Health Network. Prince Margaret Hospital. Cell Therapy Program; Canadá. University of Toronto; Canad

Alendronate inhibits triglyceride accumulation and oxidative stress in adipocytes and the inflammatory response of macrophages which are associated with adipose tissue dysfunction

Alendronate, a bisphosphonate used to prevent osteoporosis, stimulates osteogenesis but impairs adipogenesis. Different clinical trials suggest that the incidence of diabetes may be lower in patients treated with alendronate. Taking into account the importance of adipocytes and macrophages of adipose tissue in insulin resistance and type 2 diabetes, it is necessary to evaluate the effect of alendronate in both cell types. In this paper, we investigated the effect of alendronate on the differentiation to adipocytes of 3T3-L1 fibroblasts, the cell line most used to study adipogenesis, and also its effect on lipid content and oxidative stress in mature adipocytes as well as on the inflammatory response of macrophages. We found that alendronate inhibits differentiation of 3T3-L1 fibroblasts to adipocytes in keeping with reports in other cell lines. On the other hand, treatment of 3T3-L1 adipocytes with alendronate was able to decrease triglyceride content and to prevent H2O2-induced lipid peroxidation which was evaluated as an indicator of oxidative stress. In addition, it was found that activation of RAW 264.7 macrophages to a pro-inflammatory M1 type is inhibited by this bisphosphonate. These results suggest that alendronate may contribute to prevent adipocyte excessive enlargement and the induction of oxidative stress in 3T3-L1 adipocytes as well as the activation of macrophages to a pro-inflammatory M1 type, which are events associated with adipose tissue dysfunction and insulin resistance. In this study, we unraveled the underlying mechanisms of events that were previously observed in clinical trials.Fil: Martini, Claudia Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Sosa, Fernando Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Malvicini, Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Pacienza, Natalia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Yannarelli, Gustavo Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Vila, Maria del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentin

Los niveles de LDL oxidadas están asociados a la concentración de tirotrofina en individuos eutiroideos normocolesterolemicos

Las liporoteínas de baja densidad (LBL) son un consolidado factor de riesgo para la aterosclerosis...Fil: Giunta, Gustavo Ariel. Universidad Favaloro. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Lípidos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rojo, Daniela. Universidad Favaloro. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Lípidos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Duaip, Germán. Universidad Favaloro. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Lípidos; ArgentinaFil: Maggi, Liliana. Universidad Favaloro. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Lípidos; ArgentinaFil: Pacienza, Natalia Alejandra. Universidad Favaloro. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Lípidos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Yannarelli, Gustavo Gabriel. Universidad Favaloro. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Lípidos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cuniberti, Luis Alberto. Universidad Favaloro. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Lípidos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Low Oct4 expression in mesenchymal stem cells contributes to the development of the bone marrow pre-metastatic niche in advanced breast cancer patients

The imbalance between osteogenesis and osteoclastogenesis in the bone marrow (BM) microenvironment seems to play an essential role in the establishment of bone metastasis in untreated advanced breast cancer patients (BCP). We have previously found that this lack of balance is produced, among other factors, by a lower self-renewal, proliferation, and osteogenic differentiation capacity of BM-mesenchymal stem cells (MSCs). Mechanisms mediating these characteristic changes remain elusive. Here, we evaluated the expression of the osteoprogenitor marker CD146 (Flow cytometry), telomerase activity (qPCR), telomere length (qPCR), as well as the expression of the pluripotency factors Oct4 and Sox2 (qPCR) in BM-MSCs from clinical stage IIIb BCP (n=8) vs. healthy volunteers (HV; n=8). We found that MSCs from BCP had lower percentage of CD146+ cells (p=0.04), decreased CD146 relative fluorescence index (p=0.002), lower telomerase activity (p=0.04), and shortened telomere length (p=0.002) compared with HV. Moreover, Oct4 and Sox2 expression decreased by 54% (p=0.03) and 72% (p=0.009) in BCP-MSCs, respectively. Interestingly, Oct4 silencing impaired the ability of BM-MSCs to differentiate into osteoblasts (p<0.0001). In conclusion, we found that a low Oct4 expression characterizes the altered BM-MSC phenotype in BCP. This change may explain the loss of osteoprogenitors and the impairment of MSC osteogenic processes, which create an ideal environment for BM metastatic development.Fil: Sanmartin, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Borzone, Francisco Raúl. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Malvicini, Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Martinez, Leandro Marcelo. Weill Cornell Medical College; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Feldman, Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Batagelj, Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Ministerio de Defensa. Ejército Argentino. Hospital Militar Central Cirujano Mayor "Dr. Cosme Argerich"; ArgentinaFil: Pacienza, Natalia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Chasseing, Norma Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Yannarelli, Gustavo Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaBuenos Aires Breast Cancer SymposiumBuenos AiresArgentinaCentro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”Consejo Nacional de Investigaciones Científicas y TécnicasInstituto de Biología y Medicina ExperimentalInstituto de Fisiología, Biología Molecular y NeurocienciasInstituto de Investigaciones en Medicina TraslacionalInstituto de NanosistemasUniversidad AustralUniversidad de Buenos AiresUniversidad Nacional de San Martí