-
Birth Defects Research. Part C, Embryo... Mar 2012A number of organs have the intrinsic ability to regenerate, a distinctive feature that varies among organisms. Organ regeneration is a process not fully yet understood.... (Review)
Review
A number of organs have the intrinsic ability to regenerate, a distinctive feature that varies among organisms. Organ regeneration is a process not fully yet understood. However, when its underlying mechanisms are unraveled, it holds tremendous therapeutic potential for humans. In this review, we chose to summarize the repair and regenerative potential of the following organs and organ systems: thymus, adrenal gland, thyroid gland, intestine, lungs, heart, liver, blood vessels, germ cells, nervous system, eye tissues, hair cells, kidney and bladder, skin, hair follicles, pancreas, bone, and cartilage. For each organ, a review of the following is presented: (a) factors, pathways, and cells that are involved in the organ's intrinsic regenerative ability, (b) contribution of exogenous cells - such as progenitor cells, embryonic stem cells, induced pluripotent stem cells, and bone marrow-, adipose- and umbilical cord blood-derived stem cells - in repairing and regenerating organs in the absence of an innate intrinsic regenerative capability, (c) and the progress made in engineering bio-artificial scaffolds, tissues, and organs. Organ regeneration is a promising therapy that can alleviate humans from diseases that have not been yet cured. It is also superior to already existing treatments that utilize exogenous sources to substitute for the organ's lost structure and/or function(s).
Topics: Animals; Humans; Models, Animal; Organ Specificity; Regeneration; Regenerative Medicine; Stem Cell Transplantation; Stem Cells; Tissue Engineering
PubMed: 22457174
DOI: 10.1002/bdrc.21006 -
British Journal of Haematology Oct 2009We developed the strategy of umbilical cord blood transplants (UCBT) with co-infusion of a limited number of highly purified mobilized haematopoietic stem cells (MHSC)... (Review)
Review
We developed the strategy of umbilical cord blood transplants (UCBT) with co-infusion of a limited number of highly purified mobilized haematopoietic stem cells (MHSC) from a human leucocyte antigen (HLA) unrestricted third party donor (TPD). Short post-transplant periods of neutropenia were usually observed in adults with haematological neoplasms receiving UCBT with a relatively low cell content and 0-3 HLA mismatches after myeloablative conditioning. This resulted from an early and initially predominant engraftment of the TPD-MHSC. After a variable period of double complete TPD + UCB chimerism, final full UCB chimerism was achieved (cumulative incidence >90%) within 100 d. Early recovery of the circulating neutrophils resulting from the 'bridge transplant' of the TPD-MHSC reduced the incidence of serious neutropenia-related infections, also facilitating the use of drugs with myelosuppressive side effects to combat other infections. The observed incidence of graft-versus-host disease and relapses was low, with overall and disease-free survival curves comparable to those of HLA identical sibling transplants. Post-transplant recovery of natural killer cells occurred soon after the transplant and B cells recovered around 6 months, but T-cell recovery took more than 1 year. Available data show that T cell recovery derives from UCB-HSC through thymic differentiation and that cytomegalovirus (CMV)-specific lymphocytes develop following CMV reactivations.
Topics: Cord Blood Stem Cell Transplantation; Graft Rejection; Hematopoietic Stem Cell Transplantation; Histocompatibility Testing; Humans; Survival Analysis; T-Lymphocyte Subsets; Tissue Donors; Treatment Outcome
PubMed: 19796265
DOI: 10.1111/j.1365-2141.2009.07766.x -
European Review For Medical and... Oct 2014Epithelium-derived thymic stromal lymphopoietin (TSLP), is a key pro-allergic cytokine that has recently been linked to chronic airway diseases. Our aim is to determine...
OBJECTIVE
Epithelium-derived thymic stromal lymphopoietin (TSLP), is a key pro-allergic cytokine that has recently been linked to chronic airway diseases. Our aim is to determine cord blood TSLP levels in pregnancies with meconium stained amniotic fluid.
PATIENTS AND METHODS
A total of 44 pregnant women with meconium stained amniotic fluid and a total of 44 healthy pregnant women were enrolled in the study. Cord blood TSLP was measured with TSLP ELISA Kit.
RESULTS
We found no statistically significant differences between 2 groups in terms of age and parity. TSLP levels were found to be significantly higher in the cord blood of pregnant women with meconium stained amniotic fluid (104.3 ± 96.9 ng/ml) compared with the control group (63.2 ± 65.3 ng/ml) (p = 0.022).
CONCLUSIONS
It seems that TSLP is produced and released in response to meconium.
Topics: Adult; Amniotic Fluid; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Fetal Blood; Humans; Infant, Newborn; Meconium; Pregnancy; Staining and Labeling; Young Adult; Thymic Stromal Lymphopoietin
PubMed: 25392097
DOI: No ID Found -
Journal of Occupational and... Oct 2016We aimed to determine whether average and trimester-specific exposures to ambient measures of nitrogen dioxide (NO2) and particular matter (PM2.5) were associated with...
OBJECTIVES
We aimed to determine whether average and trimester-specific exposures to ambient measures of nitrogen dioxide (NO2) and particular matter (PM2.5) were associated with elevated cord blood concentrations of immunoglobulin E (IgE) and two epithelial cell produced cytokines: interleukin-33 (IL-33) and thymic stromal lymphopoietin (TSLP).
METHODS
This study utilized data and biospecimens from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study. There were 2001 pregnant women recruited between 2008 and 2011 from 10 Canadian cities. Maternal exposure to NO2 and PM2.5 was estimated using land use regression and satellite-derived models.
RESULTS
We observed statistically significant associations between maternal NO2 exposure and elevated cord blood concentrations of both IL-33 and TSLP among girls but not boys.
CONCLUSIONS
Maternal NO2 exposure may impact the development of the newborn immune system as measured by cord blood concentrations of two cytokines.
Topics: Air Pollution; Biomarkers; Canada; Cities; Cytokines; Female; Fetal Blood; Humans; Immune System; Immunoglobulin E; Infant, Newborn; Interleukin-33; Male; Maternal Exposure; Nitric Oxide; Nitrogen Dioxide; Particulate Matter; Pregnancy; Thymic Stromal Lymphopoietin
PubMed: 27483336
DOI: 10.1097/JOM.0000000000000841 -
Cell and Tissue Research Feb 2015We provide evidence for the compartmentalization of the avian thymic medulla and identify the avian thymic dendritic cell. The thymic anlage develops from an epithelial...
We provide evidence for the compartmentalization of the avian thymic medulla and identify the avian thymic dendritic cell. The thymic anlage develops from an epithelial cord of the branchial endoderm. Branches of the cord are separated by primary septae of neural crest origin. The dilation of the primary septae produces the keratin-negative area (KNA) of the thymic medulla and fills the gaps of the keratin-positive network (KPN). Morphometric analysis indicates that the KNA takes up about half of the volume of the thymic medulla, which has reticular connective tissue, like peripheral lymphoid organs. The KNA receives blood vessels and in addition to pericytes, the myoid cells of striated muscle structure occupy this area. The myoid cells are of branchial arch or prechordal plate origin providing indirect evidence for the neural crest origin of the KNA. The marginal epithelial cells of the KPN co-express keratin and vimentin intermediate filaments, which indicate their functional peculiarity. The basal lamina of the primary septum is discontinuous on the surface of the KPN providing histological evidence for the loss of the blood-thymus barrier in the medulla. In the center of the KNA, the dendritic cells lie in close association with blood vessels, whereas the B-cells accumulate along the KPN. The organization of the KPN and KNA increases the "surface" of the so-called cortico-medullary border, thereby contributing to the efficacy of central tolerance.
Topics: Animals; Chick Embryo; Chickens; Collagen; Extracellular Matrix; Keratins; Thymus Gland
PubMed: 25381569
DOI: 10.1007/s00441-014-2027-1 -
Blood Feb 2002Cord blood (CB) is used increasingly as a source of hematopoietic stem cells because of a lower risk of acute and chronic graft-versus-host disease (GVHD). However,... (Comparative Study)
Comparative Study
Cord blood (CB) is used increasingly as a source of hematopoietic stem cells because of a lower risk of acute and chronic graft-versus-host disease (GVHD). However, there is some concern regarding the ability to adequately reconstitute host immune response due to the immaturity and naivety of CB T cells. This study was designed to evaluate T-cell reconstitution using combined approaches of phenotyping, analysis of alphabeta T-cell receptor (TCR) diversity, and assessment of ex vivo thymic function by measuring TCR rearrangement excision circles (TRECs). Ten patients who underwent CB transplantation for high-risk hematologic disorders were compared to a reference group of 19 age- and GVHD-matched patients who underwent transplantation with non-T cell-depleted bone marrow from an HLA-identical sibling donor. TREC values correlated with the relative number of naive T cells and with TCR repertoire polyclonality. During the first year after transplantation, TCR repertoires were highly abnormal and TREC values low in both groups. Notably, 2 years after transplantation onward TREC values as well as TCR diversity were higher in CB recipients than in recipients of bone marrow transplants. These data indicate an efficient thymic regeneration pathway from CB lymphoid progenitors despite the low number of cells infused compared to bone marrow, arguing for a complete clinical immune recovery after CB transplantation.
Topics: Adolescent; Adult; Bone Marrow Transplantation; Child; Child, Preschool; Female; Fetal Blood; Follow-Up Studies; Graft vs Host Reaction; Hematologic Diseases; Hematopoietic Stem Cell Transplantation; Humans; Immune System; Immunophenotyping; Leukopoiesis; Male; Middle Aged; Prognosis; Receptors, Antigen, T-Cell, alpha-beta; T-Lymphocytes; Thymus Gland; Treatment Outcome
PubMed: 11830500
DOI: 10.1182/blood.v99.4.1458 -
Clinical Immunology and Immunopathology Dec 1987We studied the in vitro effect of three different thymic factors on the expression of CD38 (T10) antigen on cord T-lymphoid cell surface. The results showed that cord...
We studied the in vitro effect of three different thymic factors on the expression of CD38 (T10) antigen on cord T-lymphoid cell surface. The results showed that cord mononuclear cell populations contain variable percentages of CD38+ cells. The CD38 molecule was expressed on cord T and B lymphocyte and monocyte surfaces. Incubation with thymic agents induced a significant increases in the CD38+ cell percentage only in the samples with low CD38 antigen expression, and this modulation was mainly attributable to the T-cell subset. The effect seems to be specific and not correlated with the known high spontaneous DNA synthesis rate of cord mononuclear cells.
Topics: ADP-ribosyl Cyclase; ADP-ribosyl Cyclase 1; Adult; Antigens, CD; Antigens, Differentiation; Fetal Blood; Fluorescent Antibody Technique; Humans; Idoxuridine; Infant, Newborn; Membrane Glycoproteins; Rosette Formation; T-Lymphocytes; Thymus Hormones
PubMed: 3315336
DOI: 10.1016/0090-1229(87)90085-7 -
Journal of Clinical Neuroscience :... Jun 2011Thymic carcinomas (TC) are rare tumors, representing 0.2% to 1.5% of all malignancies, with extrathoracic metastases to liver, kidney and bone occurring in 1% to 15% of...
Thymic carcinomas (TC) are rare tumors, representing 0.2% to 1.5% of all malignancies, with extrathoracic metastases to liver, kidney and bone occurring in 1% to 15% of patients. Although TC exhibit highly aggressive biological behavior, spinal metastasis with cord compression is rare. We describe a 57-year-old man with a 2-month history of cervicodorsal pain diagnosed with TC with primary spinal metastasis. We conclude that TC should be considered in the differential diagnosis in patients who have developed spine metastatic tumors. Early detection and appropriate surgical treatment can lead to preservation of spinal stability and neurologic improvement.
Topics: Humans; Magnetic Resonance Imaging; Male; Middle Aged; Spinal Cord Compression; Spinal Neoplasms; Thymoma; Thymus Neoplasms
PubMed: 21435886
DOI: 10.1016/j.jocn.2010.08.038 -
International Archives of Allergy and... 2021There is a growing need for early biomarkers that may predict the development of atopic dermatitis (AD). As alterations in skin barrier may be a primary event in disease...
BACKGROUND
There is a growing need for early biomarkers that may predict the development of atopic dermatitis (AD). As alterations in skin barrier may be a primary event in disease pathogenesis, epithelial cell (EC) cytokines expression patterns may be a potential biomarker in early life to target allergy preventive strategies towards "at-risk" infants.
OBJECTIVES
The aim of this longitudinal investigation was to examine from birth over the course of infancy levels of the EC cytokines: thymic stromal lymphopoietin (TSLP), interleukin (IL)-33, IL-25, and IL-17 in infants at high-risk of AD due to maternal atopy.
METHOD
We collected (n = 31) cord blood samples from atopic mothers and followed up their infants at 4-6 and 12 months of age for collection of peripheral venous blood samples and diagnosis of AD. TSLP concentration was measured by ELISA after acetone precipitation of the samples. IL-33, IL-25, and IL-17 levels were measured by Luminex.
RESULTS
Seven infants who developed AD had lower levels of IL-25 and IL-17 at birth compared to the 24 infants who did not develop AD by 12 months of age.
CONCLUSIONS
Lower cord blood levels of IL-17 and IL-25, but not other EC cytokines, were associated with the onset of AD during infancy. Our results highlight that the in-utero period appears critical, and potential maternal influences on cord blood EC-derived cytokine concentrations requires further exploration.
Topics: Biomarkers; Cytokines; Dermatitis, Atopic; Epithelial Cells; Female; Fetal Blood; Humans; Infant; Interleukin-17; Maternal Exposure; Pregnancy; Prenatal Exposure Delayed Effects; Prognosis; Thymic Stromal Lymphopoietin
PubMed: 33412547
DOI: 10.1159/000512919 -
PloS One 2018An accumulating body of evidence suggests that development of autoimmune pathologies leads to thymic dysfunction and changes in peripheral T-cell compartment, which, in... (Comparative Study)
Comparative Study
An accumulating body of evidence suggests that development of autoimmune pathologies leads to thymic dysfunction and changes in peripheral T-cell compartment, which, in turn, perpetuate their pathogenesis. To test this hypothesis, thymocyte differentiation/maturation in rats susceptible (Dark Agouti, DA) and relatively resistant (Albino Oxford, AO) to experimental autoimmune encephalomyelitis (EAE) induction was examined. Irrespective of strain, immunization for EAE (i) increased the circulating levels of IL-6, a cytokine causally linked with thymic atrophy, and (ii) led to thymic atrophy reflecting partly enhanced thymocyte apoptosis associated with downregulated thymic IL-7 expression. Additionally, immunization diminished the expression of Thy-1, a negative regulator of TCRαβ-mediated signaling and activation thresholds, on CD4+CD8+ TCRαβlo/hi thymocytes undergoing selection and thereby impaired thymocyte selection/survival. This diminished the generation of mature CD4+ and CD8+ single positive TCRαβhi thymocytes and, consequently, CD4+ and CD8+ recent thymic emigrants. In immunized rats, thymic differentiation of natural regulatory CD4+Foxp3+CD25+ T cells (nTregs) was particularly affected reflecting a diminished expression of IL-7, IL-2 and IL-15. The decline in the overall thymic T-cell output and nTreg generation was more pronounced in DA than AO rats. Additionally, differently from immunized AO rats, in DA ones the frequency of CD28- cells secreting cytolytic enzymes within peripheral blood CD4+ T lymphocytes increased, as a consequence of thymic atrophy-related replicative stress (mirrored in CD4+ cell memory pool expansion and p16INK4a accumulation). The higher circulating level of TNF-α in DA compared with AO rats could also contribute to this difference. Consistently, higher frequency of cytolytic CD4+ granzyme B+ cells (associated with greater tissue damage) was found in spinal cord of immunized DA rats compared with their AO counterparts. In conclusion, the study indicated that strain differences in immunization-induced changes in thymopoiesis and peripheral CD4+CD28- T-cell generation could contribute to rat strain-specific clinical outcomes of immunization for EAE.
Topics: Animals; Apoptosis; Atrophy; Cell Proliferation; Encephalomyelitis, Autoimmune, Experimental; Female; Immunization; Random Allocation; Rats; Species Specificity; Thymocytes; Thymus Gland
PubMed: 30086167
DOI: 10.1371/journal.pone.0201848