Matične ćelije zubne pulpe i njihov potencijalni značaj u regenerativnoj medicini

To date, three types of dental stem cells have been isolated: Dental Pulp Stem Cells (DPSC), Stem Cells From Human Exfoliated Deciduous Teeth (SHED) and Immature Dental Pulp Stem Cells (IDPC). These dental stem cells are considered as mesenchymal stem cells. They reside within the perivascular niche of dental pulp. They are highly proliferative, clonogenic, multipotent and are similar to mesenchymal Bone Marrow Stem Cells (BMSC). Also, they have high plasticity and can be easy isolated. The expressions of the alkaline phosphatase gene, dentin matrix protein 1 and dentinsialophosphoprotein are verified in these cells. Analyses of gene expression patterns indicated several genes which encode extracellular matrix components, cell adhesion molecules, growth factors and transcription regulators, cell signaling, cell communication or cell metabolism. In both conditions, in vivo and in vitro, these cells have the ability to differentiate into odontoblasts, chondrocytes, osteoblasts, adipocytes, neurons, melanocytes, smooth and skeletal muscles and endothelial cells. In vivo, after implantation, they have shown potential to differentiate into dentin but also into tissues like bone, adipose or neural tissue. In general, DPSCs are considered to have antiinflammatory and immunomodulatory abilities. After being grafted into allogenic tissues these cells are ableto induce immunological tolerance. Immunosuppressive effect is shown through the ability to inhibit proliferation of T lymphocytes. Dental pulp stem cells open new perspectives in therapeutic use not only in dentin regeneration, periodontal tissues and skeletoarticular, tissues of craniofacial region but also in treatment of neurotrauma, autoimmune diseases, myocardial infarction, muscular dystrophy and connective tissue damages.Iz zubne pulpe su do danas izolovane tri populacije matičnih ćelija koje su označene kao matične ćelije zubne pulpe (engl. Dental Pulp Stem Cells, DPSC), matične ćelije iz eksfoliranih mlečnih zuba (engl. Stem Cells From Human Exfoliated Decidual Teeth, SHED) i nezrele matične ćelije zubne pulpe (engl. Immature Dental Pulp Stem Cells, IDPC). Sve matične ćelije zubne pulpe su ektomezenhimalnog porekla i lokalizovane su u perivaskularnoj niši. One se lako i efikasno izoluju, visoko su proliferativne, klonogene, multipotentne, ispoljavaju visok stepen plasticiteta i i slične su mezenhimalnim matičnim ćelijama koštane srži (BMSC). U njima je pokazana visoka ekspresija gena alkalne fosfataze, proteina 1 matriksa dentina i dentin-sijalofosfoproteina. Takođe, istaknuta je važnost u ovim ćelijama ekspresije više gena koji kodiraju sintezu komponenti ekstracelularnog matriksa, molekula ćelijske adhezije, faktora rasta, transkripcionih faktora, gena prenosa ćelijskih signala, ćelijske komunikacije i metabolizma. U uslovima in vitro ili in vivo ove ćelije mogu da se diferenciraju, s određenim međusobnim razlikama, u pravcu odontoblasta, hondrocita, osteoblasta, adipocita, neurona/glije, glatkih i skeletnih mišićnih ćelija, endotelnih ćelija i melanocita. U uslovima in vivo, nakon implantacije, pokazuju različit potencijal za formiranje dentina, ali i koštanog, masnog i nervnog tkiva. Generalno se smatra da DPSC imaju anti-inflamatorno dejstvo i ispoljavaju imunom-odulatorni efekat. Takođe, dovode do imunološke tolerancije ukoliko se implantiraju u alogena tkiva. Sposobnost inhibicije proliferacije T limfocita ukazuje na njihovo imunosupresivno dejstvo. Matične ćelije zubne pulpe otvorile su nove perspektive u terapijskoj primeni ovih ćelija ne samo u regeneraciji dentina, tkiva periodoncijuma i koštano-zglobnog tkiva kraniofacijalne regije, već i u lečenju neurotraume, autoimunskih oboljenja, infarkta miokarda, mišićne distrofije i oštećenja vezivnog tkiva

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Dental pulp stem cells: Potential significance in regenerative medicine

To date, three types of dental stem cells have been isolated: Dental Pulp Stem Cells (DPSC), Stem Cells From Human Exfoliated Deciduous Teeth (SHED) and Immature Dental Pulp Stem Cells (IDPC). These dental stem cells are considered as mesenchymal stem cells. They reside within the perivascular niche of dental pulp. They are highly proliferative, clonogenic, multipotent and are similar to mesenchymal Bone Marrow Stem Cells (BMSC). Also, they have high plasticity and can be easy isolated. The expressions of the alkaline phosphatase gene, dentin matrix protein 1 and dentinsialophosphoprotein are verified in these cells. Analyses of gene expression patterns indicated several genes which encode extracellular matrix components, cell adhesion molecules, growth factors and transcription regulators, cell signaling, cell communication or cell metabolism. In both conditions, in vivo and in vitro, these cells have the ability to differentiate into odontoblasts, chondrocytes, osteoblasts, adipocytes, neurons, melanocytes, smooth and skeletal muscles and endothelial cells. In vivo, after implantation, they have shown potential to differentiate into dentin but also into tissues like bone, adipose or neural tissue. In general, DPSCs are considered to have antiinflammatory and immunomodulatory abilities. After being grafted into allogenic tissues these cells are ableto induce immunological tolerance. Immunosuppressive effect is shown through the ability to inhibit proliferation of T lymphocytes. Dental pulp stem cells open new perspectives in therapeutic use not only in dentin regeneration, periodontal tissues and skeletoarticular, tissues of craniofacial region but also in treatment of neurotrauma, autoimmune diseases, myocardial infarction, muscular dystrophy and connective tissue damages