A triple-transgenic (tyrosine hydroxylase/dopamine decarboxylase/GTP cyclohydrolase 1, TH/DDC/GCH1) bone marrow mesenchymal stem cell line (BMSCs) capable of stably synthesizing dopamine (DA) transmitters were established to provide experimental evidence for the clinical treatment of Parkinson's disease (PD) by using this cell line. The DA-BMSCs cell line that could stably synthesize and secrete DA transmitters was established by using the triple transgenic recombinant lentivirus. The triple transgenes (TH/DDC/GCH1) expression in DA-BMSCs was detected using reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and immunofluorescence. Moreover, the secretion of DA was tested by enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography (HPLC). Chromosome G-banding analysis was used to detect the genetic stability of DA-BMSCs. Subsequently, the DA-BMSCs were stereotactically transplanted into the right medial forebrain bundle (MFB) of Parkinson's rat models to detect their survival and differentiation in the intracerebral microenvironment of PD rats. Apomorphine (APO)-induced rotation test was used to detect the improvement of motor dysfunction in PD rat models with cell transplantation. The TH, DDC and GCH1 were expressed stably and efficiently in the DA-BMSCs cell line, but not expressed in the normal rat BMSCs. The concentration of DA in the cell culture supernatant of the triple transgenic group (DA-BMSCs) and the LV-TH group was extremely significantly higher than that of the standard BMSCs control group (P < 0.000 1). After passage, DA-BMSCs stably produced DA. Karyotype G-banding analysis showed that the vast majority of DA-BMSCs maintained normal diploid karyotypes (94.5%). Moreover, after 4 weeks of transplantation into the brain of PD rats, DA-BMSCs significantly improved the movement disorder of PD rat models, survived in a large amount in the brain microenvironment, differentiated into TH-positive and GFAP-positive cells, and upregulated the DA level in the injured area of the brain. The triple-transgenic DA-BMSCs cell line that stably produced DA, survived in large numbers, and differentiated in the rat brain was successfully established, laying a foundation for the treatment of PD using engineered culture and transplantation of DA-BMSCs.
Rats ; Animals ; Dopamine ; Parkinson Disease/metabolism* ; Mesenchymal Stem Cells/metabolism* ; Cell Line ; Brain/metabolism* ; Cell Differentiation ; Mesenchymal Stem Cell Transplantation

Salivary gland (SG) dysfunction, due to radiotherapy, disease, or aging, is a clinical manifestation that has the potential to cause severe oral and/or systemic diseases and compromise quality of life. Currently, the standard-of-care for this condition remains palliative. A variety of approaches have been employed to restore saliva production, but they have largely failed due to damage to both secretory cells and the extracellular matrix (niche). Transplantation of allogeneic cells from healthy donors has been suggested as a potential solution, but no definitive population of SG stem cells, capable of regenerating the gland, has been identified. Alternatively, mesenchymal stem cells (MSCs) are abundant, well characterized, and during SG development/homeostasis engage in signaling crosstalk with the SG epithelium. Further, the trans-differentiation potential of these cells and their ability to regenerate SG tissues have been demonstrated. However, recent findings suggest that the "immuno-privileged" status of allogeneic adult MSCs may not reflect their status post-transplantation. In contrast, autologous MSCs can be recovered from healthy tissues and do not present a challenge to the recipient's immune system. With recent advances in our ability to expand MSCs in vitro on tissue-specific matrices, autologous MSCs may offer a new therapeutic paradigm for restoration of SG function.
Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells ; Quality of Life ; Regeneration ; Salivary Glands ; Stem Cells

Wound healing involves complex pathophysiological mechanism, among which angiogenesis is considered as one of the key steps in wound healing, and promoting wound angiogenesis can accelerate wound healing. In recent years, mesenchymal stem cell-derived extracellular vesicles have been proven to produce equivalent effects of wound healing promotion comparable to stem cell therapy, with the advantages of low antigenicity and high biocompatibility. The specific mechanism by which extracellular vesicles facilitate wound healing is still not fully understood and is thought to involve all stages of wound healing. This article focuses on the possible mechanism of extracellular vesicles of adipose-derived mesenchymal stem cells in promoting wound angiogenesis, so as to provide ideas for further study on the mechanism of extracellular vesicles to promote wound healing.
Wound Healing/physiology* ; Mesenchymal Stem Cells ; Extracellular Vesicles ; Stem Cell Transplantation

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

Humans ; Infant ; Infant, Newborn ; Infant, Extremely Low Birth Weight ; Mesenchymal Stem Cell Transplantation ; Umbilical Cord/cytology* ; Skin/injuries*

Ex vivo culture-amplified mesenchymal stem cells (MSCs) have been studied because of their capacity for healing tissue injury. MSC transplantation is a valid approach for promoting the repair of damaged tissues and replacement of lost cells or to safeguard surviving cells, but currently the efficiency of MSC transplantation is constrained by the extensive loss of MSCs during the short post-transplantation period. Hence, strategies to increase the efficacy of MSC treatment are urgently needed. Iron overload, reactive oxygen species deposition, and decreased antioxidant capacity suppress the proliferation and regeneration of MSCs, thereby hastening cell death. Notably, oxidative stress (OS) and deficient antioxidant defense induced by iron overload can result in ferroptosis. Ferroptosis may inhibit cell survival after MSC transplantation, thereby reducing clinical efficacy. In this review, we explore the role of ferroptosis in MSC performance. Given that little research has focused on ferroptosis in transplanted MSCs, further study is urgently needed to enhance the in vivo implantation, function, and duration of MSCs.
Humans ; Antioxidants/metabolism* ; Ferroptosis ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells ; Iron Overload/metabolism*

Stem cells have been a hot spot in medical research for a long time and have unique advantages in tissue repair, diagnosis and treatment of diseases. With the development of regenerative medicine, stem cells have been widely studied and applied in reproductive medicine, such as improving ovarian function and repairing endometrial damage. These efforts are achieved primarily through the use of mesenchymal stem cells(MSCs) from a variety of sources. However, the application of stem cells also faces problems such as low cell retention rate and medical ethics. This article focuses on the research progress and clinical application of MSCs (not involving embryonic stem cells) in the field of female reproductive medicine.
Humans ; Female ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells ; Regenerative Medicine ; Signal Transduction

In recent years, the application of cell-based therapy in the field of refractory wound repair has shown broad prospects, among which the mesenchymal stem cell is the most concerned and widely studied cell type. Despite the rapid development of clinical translational research, the therapeutic effect of cell-based therapy is not consistent, and most clinical trials have not achieved the desired results. Further studies have found that heterogeneity is an important issue that restricts the further development of cell-based therapy and urgently needs to be studied. Based on the research progress of mesenchymal stem cells, in the review, we discuss the current status and challenges of cell-based therapy strategies for refractory wounds.
Translational Research, Biomedical ; Mesenchymal Stem Cells/metabolism* ; Stem Cell Transplantation ; Wound Healing

OBJECTIVE: To obtain eripheral blood mesenchymal stem cells (PBMSCs) from sheep and rabbits by continuous mobilization of granulocyte colony-stimulating factor (G-CSF), and by comparing the success rates, cell yields and biological characteristics of the two sources of PBMSCs, and to provide the experimental basis for the preclinical study of PBMSCs transplantation to repair articular cartilage injury and cartilage tissue engineering. METHODS: Through morphological characteristics, flow cytometry analysis of its surface markers, and induction of trilineage differentiation of the two cells in vitro (ie: adipogenic differentiation, osteogenic differentiation, chondrogenic differentiation), the obtained cells were finally confirmed to be PBMSCs. The colony-forming units (CFUs) and the acquisition success rates of the two PBMSCs were counted and compared, and the production of the second generation of the two PBMSCs was counted and compared by hemocytometer, and the cell counting kit-8 was used to detect the doubling time of the two PBMSCs, and the results of trilineage differentiation were quantitatively analyzed by image processing. RESULTS: Microscopically, the PBMSCs of fusiform sheep and rabbits were arranged in fish group, and the second generation of sheep and rabbit PBMSCs expressed CD44 and CD90, but not CD34 and CD45. The induction of trilineage differentiation of the two cells in vitro were successful. The CFUs of primary sheep and rabbits PBMSCs were: 7.27±1.56, 5.73±1.62, and the success rate of acquisition of sheep and rabbits PBMSCs were 78.57% and 36.67%. The number of the second-generation sheep and rabbits PBMSCs that obtained per milliliter of peripheral blood were: 29 582±2 138, 26 732±2 286, and the cell doubling times (h) of the third-generation sheep and rabbits PBMSCs were: 22.32±0.28, 33.21±0.64, the cell doubling time (h) of the fourth generation sheep and rabbits PBMSCs were: 23.62±0.56, 35.30±0.38, and the quantitative lipid ratio of sheep and rabbit PBMSCs were: 7.77%±3.81%, 17.05%±1.52%, sheep and rabbit PBMSCs chondroglobus acid mucopolysaccharide positive ratios were: 11.67%±0.53%, 8.14%±0.57%. There were statistical differences among the above groups (P < 0.05). CONCLUSION The continuous mobilization of G-CSF to obtain sheep PBMSCs is more efficient. Sheep PBMSCs have more abundant yield and stronger proliferation ability.Sheep PBMSCs can produce more acidic mucopolysaccharides and have lower adipogenic abi-lity under appropriate conditions. Sheep PBMSCs have good research prospects in repair of articular cartilage injury with autologous stem cell transplantation and preclinical animal in vivo experiment of cartilage tissue engineering.This experiment provides further experimental basis for this kind of research.
Sheep ; Rabbits ; Animals ; Osteogenesis ; Hematopoietic Stem Cell Transplantation ; Cells, Cultured ; Transplantation, Autologous ; Mesenchymal Stem Cells ; Cell Differentiation ; Cartilage, Articular/injuries* ; Granulocyte Colony-Stimulating Factor

Asthma,a chronic inflammatory disease of respiratory system,is characterized by airway hyperresponsiveness,chronic airway inflammation,mucus secretion,and airway remodeling.Mesenchymal stem cell (MSC) are a kind of multifunctional stem cells,which have the ability of self-renewal and multi-directional differentiation.They are involved in a variety of physiological processes,such as immune response,antigen presentation,inflammatory response,and cell migration.MSCs plays a key role in the pathogenesis of bronchial asthma,while the underlying mechanism remains to be studied.MSC are a potential target for the treatment of bronchial asthma.This paper reviews the mechanism of MSC in the treatment of asthma.
Humans ; Animals ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells ; Asthma/therapy* ; Airway Remodeling ; Cell Differentiation ; Disease Models, Animal