The teeth are highly differentiated chewing organs formed by the development of tooth germ tissue located in the jaw and consist of the enamel, dentin, cementum, pulp, and periodontal tissue. Moreover, the teeth have a complicated regulatory mechanism, special histologic origin, diverse structure, and important function in mastication, articulation, and aesthetics. These characteristics, to a certain extent, greatly complicate the research in tooth regeneration. Recently, new ideas for tooth and tissue regeneration have begun to appear with rapid developments in the theories and technologies in tissue engineering. Numerous types of stem cells have been isolated from dental tissue, such as dental pulp stem cells (DPSCs), stem cells isolated from human pulp of exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSCs), stem cells from apical papilla (SCAPs), and dental follicle cells (DFCs). All these cells can regenerate the tissue of tooth. This review outlines the cell types and strategies of stem cell therapy applied in tooth regeneration, in order to provide theoretical basis for clinical treatments.
Adult Stem Cells ; physiology ; Animals ; Cell Differentiation ; Humans ; Stem Cell Transplantation ; Tissue Engineering ; Tooth ; cytology ; growth & development ; physiology ; Wound Healing

BACKGROUNDSteady-state bone marrow (SS-BM) and granulocyte colony-stimulating growth factor-primed BM/peripheral blood stem-cell (G-BM/G-PBSC) are the main stem-cell sources used in allogeneic hematopoietic stem-cell transplantation. Here, we evaluated the treatment effects of SS-BM and G-BM/G-PBSC in human leucocyte antigen (HLA)-identical sibling transplantation.

METHODSA total of 226 patients (acute myelogenous leukemia-complete remission 1, chronic myelogenous leukemia-chronic phase 1) received SS-BM, G-BM, or G-PBSC from an HLA-identical sibling. Clinical outcomes (graft-versus-host disease [GVHD], overall survival, transplant-related mortality [TRM], and leukemia-free survival [LFS]) were analyzed.

RESULTSWhen compared to SS-BM, G-BM gave faster recovery time to neutrophil or platelet (P < 0.05). Incidence of grade III-IV acute GVHD and extensive chronic GVHD (cGVHD) was lower than seen with SS-BM (P < 0.05) and similar to G-PBSC. Although the incidence of cGVHD in the G-BM group was similar to SS-BM, both were lower than G-PBSC (P < 0.05). G-BM and G-PBSC exhibited similar survival, LFS, and TRM, but were significantly different from SS-BM (P < 0.05). There were no significant differences in leukemia relapse rates among the groups (P > 0.05).

CONCLUSIONSG-CSF-primed bone marrow shared the advantages of G-PBSC and SS-BM. We conclude that G-BM is an excellent stem-cell source that may be preferable to G-PBSC or SS-BM in patients receiving HLA-identical sibling hematopoietic stem-cell transplantation.

Adolescent ; Adult ; Aged ; Bone Marrow ; drug effects ; Bone Marrow Transplantation ; methods ; Child ; Female ; Granulocyte Colony-Stimulating Factor ; pharmacology ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; therapy ; Leukemia, Myeloid, Acute ; therapy ; Male ; Middle Aged ; Retrospective Studies ; Stem Cells ; cytology ; Young Adult

Acute graft-versus-host disease (aGVHD) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the mechanisms of aGVHD are not well understood. We aim to investigate the roles of the three angiogenic factors: angiopoietin-1 (Ang-1), Ang-2 and vascular endothelial growth factor (VEGF) in the development of aGVHD. Twenty-one patients who underwent allo-HSCT were included in our study. The dynamic changes of Ang-1, Ang-2 and VEGF were monitored in patients before and after allo-HSCT. In vitro, endothelial cells (ECs) were treated with TNF-β in the presence or absence of Ang-1, and then the Ang-2 level in the cell culture medium and the tubule formation by ECs were evaluated. After allo-HSCT, Ang-1, Ang-2 and VEGF all exhibited significant variation, suggesting these factors might be involved in the endothelial damage in transplantation. Patients with aGVHD had lower Ang-1 level at day 7 but higher Ang-2 level at day 21 than those without aGVHD, implying that Ang-1 may play a protective role in early phase yet Ang-2 is a promotion factor to aGVHD. In vitro, TNF-β promoted the release of Ang-2 by ECs and impaired tubule formation of ECs, which were both weakened by Ang-1, suggesting that Ang-1 may play a protective role in aGVHD by influencing the secretion of Ang-2, consistent with our in vivo tests. It is concluded that monitoring changes of these factors following allo-HSCT might help to identify patients at a high risk for aGVHD.
Acute Disease ; Adolescent ; Adult ; Angiogenesis Inducing Agents ; immunology ; metabolism ; pharmacology ; Angiopoietin-1 ; genetics ; immunology ; pharmacology ; Angiopoietin-2 ; genetics ; immunology ; pharmacology ; Antineoplastic Agents ; therapeutic use ; Female ; Gene Expression Regulation, Neoplastic ; Graft vs Host Disease ; genetics ; immunology ; pathology ; Hematopoietic Stem Cell Transplantation ; Human Umbilical Vein Endothelial Cells ; cytology ; drug effects ; immunology ; Humans ; Leukemia, Myeloid ; genetics ; immunology ; pathology ; therapy ; Lymphoma, Non-Hodgkin ; genetics ; immunology ; pathology ; therapy ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; immunology ; pathology ; therapy ; Retrospective Studies ; Signal Transduction ; Transplantation, Homologous ; Tumor Necrosis Factor-alpha ; pharmacology ; Vascular Endothelial Growth Factor A ; genetics ; immunology

Adipose tissue stem cells (ADSCs) would be an attractive autologous cell source. However, ADSCs require invasive procedures, and has potential complications. Recently, urine stem cells (USCs) have been proposed as an alternative stem cell source. In this study, we compared USCs and ADSCs collected from the same patients on stem cell characteristics and capacity to differentiate into various cell lineages to provide a useful guideline for selecting the appropriate type of cell source for use in clinical application. The urine samples were collected via urethral catheterization, and adipose tissue was obtained from subcutaneous fat tissue during elective laparoscopic kidney surgery from the same patient (n = 10). Both cells were plated for primary culture. Cell proliferation, colony formation, cell surface markers, immune modulation, chromosome stability and multi-lineage differentiation were analyzed for each USCs and ADSCs at cell passage 3, 5, and 7. USCs showed high cell proliferation rate, enhanced colony forming ability, strong positive for stem cell markers expression, high efficiency for inhibition of immune cell activation compared to ADSCs at cell passage 3, 5, and 7. In chromosome stability analysis, both cells showed normal karyotype through all passages. In analysis of multi-lineage capability, USCs showed higher myogenic, neurogenic, and endogenic differentiation rate, and lower osteogenic, adipogenic, and chondrogenic differentiation rate compared to ADSCs. Therefore, we expect that USC can be an alternative autologous stem cell source for muscle, neuron and endothelial tissue reconstruction instead of ADSCs.
Adult Stem Cells/*cytology/*immunology/transplantation ; Biomarkers/metabolism ; Cell Differentiation ; Cell Lineage ; Cell Proliferation ; Cell Separation ; Chromosomal Instability ; Colony-Forming Units Assay ; Humans ; Karyotyping ; Multipotent Stem Cells/cytology/immunology/transplantation ; Subcutaneous Fat, Abdominal/*cytology ; Transplantation, Autologous ; Urine/*cytology

We conducted this study to investigate the synergistic effect of human urine-derived stem cells (USCs) and surface modified composite scaffold for bladder reconstruction in a rat model. The composite scaffold (Polycaprolactone/Pluronic F127/3 wt% bladder submucosa matrix) was fabricated using an immersion precipitation method, and heparin was immobilized on the surface via covalent conjugation. Basic fibroblast growth factor (bFGF) was loaded onto the heparin-immobilized scaffold by a simple dipping method. In maximal bladder capacity and compliance analysis at 8 weeks post operation, the USCs-scaffold(heparin-bFGF) group showed significant functional improvement (2.34 ± 0.25 mL and 55.09 ± 11.81 microL/cm H2O) compared to the other groups (2.60 ± 0.23 mL and 56.14 ± 9.00 microL/cm H2O for the control group, 1.46 ± 0.18 mL and 34.27 ± 4.42 microL/cm H2O for the partial cystectomy group, 1.76 ± 0.22 mL and 35.62 ± 6.69 microL/cm H2O for the scaffold group, and 1.92 ± 0.29 mL and 40.74 ± 7.88 microL/cm H2O for the scaffold(heparin-bFGF) group, respectively). In histological and immunohistochemical analysis, the USC-scaffold(heparin-bFGF) group showed pronounced, well-differentiated, and organized smooth muscle bundle formation, a multi-layered and pan-cytokeratin-positive urothelium, and high condensation of submucosal area. The USCs seeded scaffold(heparin-bFGF) exhibits significantly increased bladder capacity, compliance, regeneration of smooth muscle tissue, multi-layered urothelium, and condensed submucosa layers at the in vivo study.
Adult Stem Cells/cytology/metabolism/*transplantation ; Animals ; Biocompatible Materials/chemistry ; Cell Differentiation ; Fibroblast Growth Factor 2/administration & dosage ; Heparin/administration & dosage ; Humans ; Materials Testing ; Models, Animal ; Poloxamer ; Polyesters ; Rats ; Reconstructive Surgical Procedures ; Regeneration ; Tissue Engineering/*methods ; Tissue Scaffolds/chemistry ; Urinary Bladder/anatomy & histology/physiology/*surgery ; Urine/*cytology

Mesenchymal stem cells (MSCs) are adult stem cells which derived from the embryonic mesoderm. They have a high proliferative ability and can differentiate into various tissues of mesodermal origin including bone, cartilage and adipose tissue in vitro. Moreover, MSCs have also been shown to produce anti-inflammatory molecules which can modulate cellular and humoral immune responses. Because of their easy preparation, the capacity for self-renewal, multi-lineage differentiation and immunoregulatory effect, MSCs therapy becomes a promising tool in the treatment of tissue regeneration, anti-inflammation, and autoimmune diseases. In this review we will focus on the application of MSCs for nasal inflammation disease.
Adult Stem Cells ; transplantation ; Autoimmune Diseases ; Cell Differentiation ; Humans ; Inflammation ; therapy ; Mesenchymal Stem Cell Transplantation ; Mesoderm ; cytology ; Nose Diseases ; therapy ; Wound Healing

This study was purposed to investigate the effect of umbilical cord mesenchymal cells (UC-MSC) infusion on the pulmonary infection in haploidentical hematopoietic stem cell transplantation (hi-HSCT). The infection of 83 patients underwent hi-HSCT was detected and analysed, among them 42 patients received haploidentical hi-HSCT, 41 received hi-HSCT combined with UC-MSC infusion. The results showed that 31 cases (73.81% ± 6.78%) were infected by cytomegalovirus and 21 cases in patients received hi-HSCT experienced pulmonary infections, including infections of fungal, virus, bacteria, tubercle bacillus, PCP and so on, the incidence rate was (50 ± 7.72)%; the infection of cytomegalovirus (CMV) was found in 31 cases, the incidence rate was (78.05 ± 6.46)%. In patients received hi-HSCT combined with UC-MSC, only 15 patients experienced pulmonary infection, the incidence rate was (36.59 ± 7.52)%, and the infection of cytomegalovirus (CMV) was observed in 32 patients, the incidence rate was (78.05 ± 6.46)%. There was no obvious statistical difference between two groups(P > 0.05). It is concluded that the UC-MSC infusion not increases the infection rate in hi-HSCT.
Adolescent ; Adult ; Child ; Child, Preschool ; Cytomegalovirus Infections ; epidemiology ; Female ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Lung Diseases ; epidemiology ; Male ; Mesenchymal Stromal Cells ; cytology ; Transplantation Conditioning ; Transplantation, Homologous ; Treatment Outcome ; Umbilical Cord ; cytology ; Young Adult

Recent studies suggest that the intracoronary administration of bone marrow (BM)-derived mesenchymal stem cells (MSCs) may improve left ventricular function in patients with acute myocardial infarction (AMI). However, there is still argumentative for the safety and efficacy of MSCs in the AMI setting. We thus performed a randomized pilot study to investigate the safety and efficacy of MSCs in patients with AMI. Eighty patients with AMI after successful reperfusion therapy were randomly assigned and received an intracoronary administration of autologous BM-derived MSCs into the infarct related artery at 1 month. During follow-up period, 58 patients completed the trial. The primary endpoint was changes in left ventricular ejection fraction (LVEF) by single-photon emission computed tomography (SPECT) at 6 month. We also evaluated treatment-related adverse events. The absolute improvement in the LVEF by SPECT at 6 month was greater in the BM-derived MSCs group than in the control group (5.9%+/-8.5% vs 1.6%+/-7.0%; P=0.037). There was no treatment-related toxicity during intracoronary administration of MSCs. No significant adverse cardiovascular events occurred during follow-up. In conclusion, the intracoronary infusion of human BM-derived MSCs at 1 month is tolerable and safe with modest improvement in LVEF at 6-month follow-up by SPECT. (ClinicalTrials.gov registration number: NCT01392105)
Adult ; Aged ; Bone Marrow Cells/cytology ; Cell- and Tissue-Based Therapy/*adverse effects ; Echocardiography ; Female ; Heart/physiopathology ; Humans ; Male ; Mesenchymal Stem Cell Transplantation/*adverse effects ; Mesenchymal Stromal Cells/*cytology ; Middle Aged ; Myocardial Infarction/*therapy ; Pilot Projects ; Stroke Volume ; Tomography, Emission-Computed, Single-Photon ; Transplantation, Autologous ; Treatment Outcome ; Ventricular Function, Left ; Young Adult

BACKGROUND: Numerous studies tried to find new markers that after hematopoietic stem cell transplantation predict engraftment earlier than the conventional marker, absolute neutrophil count (ANC >500/microL). Early engraftment prediction can be achieved by a marker that reflects the release of neutrophils and monocytes into the leukopenic peripheral blood. METHODS: We analyzed blood cell parameters, including cell population data such as volume, conductivity, and light scatter in 77 patients who underwent HSCT (allogeneic, n=63; autologous, n=11) to detect possible markers. RESULTS: We identified 2 early engraftment markers of neutrophils (NEUTRO) and monocytes (MONO); a pair of mean-volume-neutrophils (MNV) and mean-conductivity-neutrophils (MNC) for NEUTRO; and a pair of mean-volume-monocytes (MMV) and mean-conductivity-monocytes (MMC) for MONO. The new markers showed distinct patterns for early engraftment wherein 1) on the engraftment day, MNV peaked as MNC notched simultaneously for every case, and 2) MMV peaked as MMC notched simultaneously in most cases. Engraftment was predicted 3.8+/-2.7 days earlier than by ANC in 74 successful engraftment cases by using NEUTRO and/or MONO: 1) 72 cases (97.3%), in which NEUTRO and/or MONO predicted earlier engraftment than ANC, 2) 1 case, in which the 3 markers predicted engraftment on the same day, and 3) 1 case, in which NEUTRO predicted engraftment on the same day as ANC and MONO failed to predict engraftment. CONCLUSIONS: By analyzing the data from daily complete blood counts, engraftment can be predicted approximately 4 days earlier than ANC >500/microL using NEUTRO as a base marker and MONO as a supplementary marker.
Adolescent ; Adult ; Child ; Child, Preschool ; Female ; *Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells/*cytology ; Humans ; Infant ; Leukocyte Count ; Male ; Middle Aged ; Monocytes/*cytology ; Neutrophils/*cytology ; Time Factors ; Transplantation, Autologous ; Transplantation, Homologous ; Young Adult

Umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) have been introduced as a possible therapy in acute lung injury and acute respiratory distress syndrome (ARDS). This case history is reported of a 59-yr-old man who was treated with MSCs in the course of ARDS and subsequent pulmonary fibrosis. He received a long period of mechanical ventilation and weaning proved difficult. On hospital day 114, he underwent the intratracheal administration of UCB-derived MSCs at a dose of 1 x 10(6)/kg. After cell infusion, an immediate improvement was shown in his mental status, his lung compliance (from 22.7 mL/cmH2O to 27.9 mL/cmH2O), PaO2/FiO2 ratio (from 191 mmHg to 334 mmHg) and his chest radiography over the course of three days. Even though he finally died of repeated pulmonary infection, our current findings suggest the possibility of using MSCs therapy in an ARDS patient. It is the first clinical case of UCB-derived MSCs therapy ever reported.
Bacterial Infections/diagnosis ; Drug Resistance, Multiple, Bacterial ; Fetal Blood/*cytology ; Humans ; Male ; *Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells/*cytology ; Middle Aged ; Respiratory Distress Syndrome, Adult/complications/radiography/*surgery ; Seizures/etiology ; Shock, Septic/diagnosis ; Tomography, X-Ray Computed ; Treatment Outcome