Dental stem cells (DSCs), an important source of mesenchymal stem cells (MSCs), can be easily obtained by minimally invasive procedures and have been used for the treatment of various diseases. Classic paradigm attributed the mechanism of their therapeutic action to direct cell differentiation after targeted migration, while contemporary insights into indirect paracrine effect opened new avenues for the mystery of their actual low engraftment and differentiation ability in vivo. As critical paracrine effectors, DSC-derived extracellular vesicles (DSC-EVs) are being increasingly linked to the positive effects of DSCs by an evolving body of in vivo studies. Carrying bioactive contents and presenting therapeutic potential in certain diseases, DSC-EVs have been introduced as promising treatments. Here, we systematically review the latest in vivo evidence that supports the therapeutic effects of DSC-EVs with mechanistic studies. In addition, current challenges and future directions for the clinical translation of DSC-EVs are also highlighted to call for more attentions to the (I) distinguishing features of DSC-EVs compared with other types of MSC-EVs, (II) heterogeneity among different subtypes of DSC-derived EVs, (III) action modes of DSC-EVs, (IV) standardization for eligible DSC-EVs and (V) safety guarantee for the clinical application of DSC-EVs. The present review would provide valuable insights into the emerging opportunities of DSC-EVs in future clinical applications.
Cell Differentiation ; Extracellular Vesicles/metabolism* ; Mesenchymal Stem Cell Transplantation/methods* ; Mesenchymal Stem Cells/metabolism*

Mesenchymal stem cells (MSCs) have been officially approved in many countries to treat graft-versus-host disease, autoimmune disorders and those associated with tissue regeneration after hematopoietic stem cell transplantation. Studies in recent years have confirmed that MSC acts mainly through paracrine mechanism, in which extracellular vesicles secreted by MSC (MSC-EV) play a central role. MSC-EV has overwhelming advantages over MSC itself in the setting of adverse effects in clinical application, indicating that MSC-EV might take the place of its parent cells to be a potentially therapeutic tool for "cell-free therapy". The pharmaceutical properties of MSC-EV largely depend upon the practical and optimal techniques including large-scale expansion of MSC, the modification of MSC based on the indications and the in vivo dynamic features of MSC-EV, and the methods for preparing and harvesting large amounts of MSC-EV. The recent progresses on the issues above will be briefly reviewed.
Humans ; Extracellular Vesicles ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Mesenchymal Stem Cell Transplantation/methods* ; Mesenchymal Stem Cells ; Pharmaceutical Preparations

This paper summarizes the current literature on the potential therapeutic role of stem cell transplantation for kidney injury and repair and focuses on the choice of types of stem cells, the method of transplantation, and the mechanisms of stem cell homing to injured renal tissues and its protective effects. The application of umbilical cord mesenchymal stem cells (UC-MSCs) shows wide prospects, but the approach and optimal dose of cell transplantation are under intensive investigation. Signals that regulate stem cell homing to injured renal tissues may be related to chemokines or factors released in the target site. Several studies have pointed out that paracrine and endocrine of stem cells are the most likely mechanism of action in the injured nephron. Many questions remain unanswered but stem cell-based therapy is a promising new strategy for acute and chronic kidney diseases.
Animals ; Cord Blood Stem Cell Transplantation ; Humans ; Kidney Diseases ; therapy ; Mesenchymal Stem Cell Transplantation ; Stem Cell Transplantation ; methods

The high incidence of chronic liver disease is a serious threat to public health, and the current comprehensive internal medicine treatment is ineffective. Liver transplantation is limited by the shortage of liver source and post-transplant rejection, and thus unmet the clinical needs. More importantly, cell therapy shows great promise for the treatment of chronic liver disease. Over recent years, domestic and foreign scholars have carried out a variety of cell therapy preclinical and clinical trials for critical liver disease, and achieved certain results, providing new methods for the treatment of chronic liver diseases. This review discusses the cell therapy research status and application progress, various existing problems and challenges, and key issues of mesenchymal stem cells in the treatment of chronic liver diseases.
Cell- and Tissue-Based Therapy ; Humans ; Liver Diseases/therapy* ; Liver Transplantation/methods* ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells

Mesenchymal stem cells (MSC) are multipotent cells able to differentiate into multiple lineages including cardiomyocytes and vascular endothelial cells under in vitro culture conditions. In vivo studies have shown that MSC can facilitate angiogenesis, and they localize to the site of ischemic injury which block or reverse the pathologic process. All the data suggest that MSC may be a promising strategy in the treatment of ischemic heart diseases. In recent years, more and more reports demonstrated that researchers have made enormous advances in this field. This review focuses on the angiogenesis and therapeutic applications of MSC derived from human bone marrow, including basic biological features of MSC, role of MSC in angiogenesis, preclinical study of MSC therapy in ischemic heart disease and prospect of MSC application in this disease.
Humans ; Mesenchymal Stem Cell Transplantation ; methods ; Mesenchymal Stromal Cells ; cytology ; Myocardial Ischemia ; surgery ; Neovascularization, Physiologic

INTRODUCTIONThis study evaluated the effect of autologous bone marrow derived adult Mesenchymal Stem Cells (MSCs) on the biological healing of weight bearing diaphyseal bone allograft in the tibia of adult rabbits.

MATERIALS AND METHODSForty Adult New Zealand White Rabbits divided into 3 groups (Autograft, Allograft or Allograft impregnated with MSCs) with 12 rabbits in each group were used for the study. A 1.5 cm of cortical bone segment was excised from the rabbit's right tibia. The segment was replaced by an Autograft, Allograft or Allograft loaded with MSCs, depending on which group the rabbit was assigned. Internal fixation was performed using a 9-hole Mini-compression Plate and Cerclage Wires. Rabbits were sacrificed at end of observation periods of 12, 16 and 24 weeks. Specimens procured were assessed clinically and radiologically and fixed in 10% buffered formalin. For each specimen, 5 μm undecalcified sections were cut and stained with Von Kossa and Toluidine Blue stains. Histomorphometery was then performed.

RESULTSOur study showed that addition of autologous MSCs to diaphyseal allograft segments enhances and accelerates not just the union at host graft junctions and also the biological incorporation of the allograft segment as shown by Resorption Index, New-Bone Formation Index and Osteocyte Index.

CONCLUSIONSThe addition of autologous MSCs to deep frozen cortical allograft segments improved the host - allograft union rate and biological incorporation of diaphyseal allografts as shown by resorption activity, new bone formation and osteocyte cell counts.

Animals ; Disease Models, Animal ; Male ; Mesenchymal Stem Cell Transplantation ; methods ; Mesenchymal Stromal Cells ; Rabbits ; Tibia ; abnormalities ; Transplantation, Homologous ; Wound Healing

Mesenchymal stem cells (MSC) are multipotent in nature and believed to facilitate the engraftment of hematopoietic stem cells (HSC) when transplanted simultaneously in animal studies and even in human trials. In this study, we transfected culture-expanded MSC with granulocyte macrophage-colony stimulating factor (GMCSF) and stem cell factor (SCF) cytokine genes and then cotransplanted with mononuclear cells (MNC) to further promote HSC engraftment. MNC were harvested from cord blood and seeded in long-term culture for ex vivo MSC expansion. A total of 1 x 10(7) MNC plus MSC/microliter were introduced to the tail vein of nonobese diabetic/severe combined immunodeficiency mice. After 6-8 weeks later, homing and engraftment of human cells were determined by flow cytometry and fluorescence in situ hybridization studies. The total nucleated cell count and the engraftment of CD45+/CD34+ cells and XX or XY positive human cells were significantly increased in cotransplanted mice and even higher with the cytokine gene-transfected MSC (GM-CSF>SCF, p<0.05) than in transplantation of MNC alone. These results suggest that MSC transfected with hematopoietic growth factor genes are capable of enhancing the hematopoietic engraftment. Delivering genes involved in homing and cell adhesions, CXCR4 or VLA, would further increase the efficiency of stem cell transplantation in the future.
Transfection/*methods ; Stem Cell Factor/genetics/*metabolism ; Mice, SCID ; Mice ; Mesenchymal Stem Cells/*metabolism ; Mesenchymal Stem Cell Transplantation/*methods ; Hematopoietic Stem Cell Transplantation/*methods ; Granulocyte Macrophage Colony-Stimulating Factors, Recombinant/*metabolism ; Graft Survival/*immunology ; Genetic Enhancement/methods ; Animals

Atherosclerosis is an inflammatory disease. However, its etiology has not been yet fully elucidated. Endothelial dysfunction is currently considered to be one of the most important steps in the initiation of atherosclerosis. In addition, vascular smooth muscle cells, which are the main cellular component of de novo and in-stent restenosis lesions, play an important role in the development of atherosclerosis. Promoting the regeneration of endothelial cells and inhibiting the proliferation of smooth muscle cells are pivotal for the prevention and treatment of vascular injury. Recently, some studies have demonstrated that mesenchymal stem cells can home to the site of injury and differentiate into endothelial cells to repair damaged blood vessels. On the contrary, other researches have revealed that mesenchymal stem cells can differentiate into vascular smooth muscle cells that are involved in the development of restenosis. Here, we review the fundamental researches of mesenchymal stem cell therapy for atherosclerosis and address the perspectives of mesenchymal stem cells in atherosclerosis treatment.
Animals ; Atherosclerosis ; therapy ; Cell Differentiation ; Cells, Cultured ; Endothelial Cells ; cytology ; Humans ; Mesenchymal Stem Cell Transplantation ; methods ; Mesenchymal Stromal Cells ; cytology

Bone marrow mesenchymal stem cells (BMSCs) are pluripotent and mostly reside in the bone marrow. Recent experimental studies on the stem cells grafting in the treatment of ischemic cerebral vascular disease have shown that BMSCs can improve neurologic impairment. As the sources of neural stem cells, they have broad prospects to be used in the treatment of ischemic cerebral vascular disease. In this review, we focus on the biological feature of BMSCs, the feasibility of transplantation, the use of BMSCs in ischemic cerebral vascular disease, and the mechanism of their action.
Bone Marrow Cells ; cytology ; Cerebral Infarction ; therapy ; Humans ; Mesenchymal Stem Cell Transplantation ; methods

OBJECTIVETo investigate the effect of segmental defects reconstruction of canine mandible with allogenenic bone marrow mesenchymal stem cells (BMSC) combined with lyophilized bone.

METHODSA 30 mm segmental defect was created on the left mandibles of beagles. Beagles were randomly divided into three groups. Allogeneic bone marrow mesenchymal stem cells with lyophilized bone were used for segmental defects reconstruction in group A. Autologous bone marrow mesenchymal stem cells with freeze- dried bone were used for segmental defects reconstruction in group B. The defects of group C were repaired with lyophilized bone only. Every three beagles were sacrificed 4, 12, 24, and 48 weeks after surgery respectively. The reconstruction effect was evaluated by CT and histopathological examination.

RESULTSCT examination showed that new bones formed in group A and group B 12 weeks after surgery, but not in group C. The form of the reconstructed mandibles in the three groups recovered in 48 weeks. The small pores on the bone graft were filled with new bones in group A and group B. In group C, the pores were still evident. Histopathological examination showed that bone trabecula between allogeneic bone and autogenous bone was completely joined in group A and group B. A large number of fibrous tissue appeared around the implanted bone and new bones were formed. In group C, the lyophilized bone resorption was still not obvious, the new bone formation was significantly slower than the other two groups. There was no difference between group A and group B.

CONCLUSIONSBoth allogeneic bone marrow mesenchymal stem cells and autologous mesenchymal stem cells could accelerate the bone formation.

Allografts ; Animals ; Bone Transplantation ; Dogs ; Mandibular Reconstruction ; methods ; Mesenchymal Stem Cell Transplantation ; Osteogenesis ; Time Factors ; Tissue Engineering ; methods