Characteristics Of Mesenchymal Stem Cells Research Articles

Therapeutic and Safety Promise of Mesenchymal Stem Cells for Liver Failure: From Preclinical Experiment to Clinical Application.

Liver failure (LF) is serious liver damage caused by multiple factors, resulting in severe impairment or decompensation of liver synthesis, detoxification, metabolism, and biotransformation. The general prognosis of LF is poor with high mortality in non-transplant patients. The clinical treatments for LF are mainly internal medicine comprehensive care, artificial liver support system, and liver transplantation. However, none of the above treatment strategies can solve the problems of all liver failure patients and has its own limitations. Mesenchymal stem cells (MSCs) are a kind of stem cells with multidirectional differentiation potential and paracrine function, which play an important role in immune regulation and tissue regeneration. In recent years, MSCs have shown multiple advantages in the treatment of LF in pre-clinical experiments and clinical trials. In this work, we reviewed the biological characteristics of MSCs, the possible molecular mechanisms of MSCs in the treatment of liver failure, animal experiments, and clinical application, and also discussed the existing problems of MSCs in the treatment of liver failure.

Anti-tumor effects of ellagic acid and mesenchymal stem cell-conditioned medium on breast cancer cells on the 3D printed PCL/agarose scaffolds

Numerous investigations have demonstrated that natural bioactive compounds, such as flavonoids, exhibit synergistic effects with anticancer agents utilized in clinical practice. Stem cell therapies play a critical role in the domain of oncology; nevertheless, conflicting results have surfaced regarding the potential pro-cancer or anti-cancer characteristics of mesenchymal stem cells. The primary aim of the current investigation was to examine the anticancer efficacy of ellagic acid (EA) alone or in combination with adipose tissue stem cells derived conditioned medium (ADSCs-CM) on human breast cancer cells. In order to overcome the potential effects of two-dimensional (2D) culture, a three-dimensional (3D) printed polycaprolactone (PCL)/agarose scaffold is utilized to evaluate cancer cell behavior. More recently it was reported this scaffold had open and interconnected pores, as well as good water absorption and mechanical properties. Assessment of MCF-7 cancer cell viability was conducted through MTT assay, flow cytometry, cell cycle assay, and quantitative real-time PCR within a 3D cell culture framework. The outcomes revealed a reduction in cancer cell viability across all treatment cohorts in comparison to the control group. Particularly noteworthy was the significantly enhanced effect of the EA and CM combination relative to each component administered individually. Flow cytometry assessment using annexin V/PI staining indicated a decrease in cancer cells, particularly evident in the combination-treated group. Furthermore, the mRNA expression levels of BAX, BCL2, vascular endothelial growth factor (VEGF), and caspase 3 genes were consistent with pathways associated with apoptosis. Consequently, the synergistic anti-proliferative impact of EA in conjunction with ADSCs-CM on MCF-7 cells has been substantiated. These findings have two important implications for breast cancer research; highlight the utility of the PCL/agarose scaffold as a cancer model and suggest new avenues for the development of adjuvant anticancer therapeutic approaches.

Revolutionizing bone defect healing: the power of mesenchymal stem cells as seeds

Bone defects can arise from trauma or pathological factors, resulting in compromised bone integrity and the loss or absence of bone tissue. As we are all aware, repairing bone defects is a core problem in bone tissue engineering. While minor bone defects can self-repair if the periosteum remains intact and normal osteogenesis occurs, significant defects or conditions such as congenital osteogenesis imperfecta present substantial challenges to self-healing. As research on mesenchymal stem cell (MSC) advances, new fields of application have emerged; however, their application in orthopedics remains one of the most established and clinically valuable directions. This review aims to provide a comprehensive overview of the research progress regarding MSCs in the treatment of diverse bone defects. MSCs, as multipotent stem cells, offer significant advantages due to their immunomodulatory properties and ability to undergo osteogenic differentiation. The review will encompass the characteristics of MSCs within the osteogenic microenvironment and summarize the research progress of MSCs in different types of bone defects, ranging from their fundamental characteristics and animal studies to clinical applications.

The Therapeutic Use of Dental Mesenchymal Stem Cells in Human Clinical Trials.

Mesenchymal stem cells (MSCs), characterized by their undifferentiated and multipotent nature, can be derived from various sources, including bone marrow, adipose, and dental tissues. Among these, dental MSCs (DSCs) exhibit universal MSC characteristics and are attracting considerable attention for regenerating oral and craniofacial tissues. This review provides a contemporary overview of recently published clinical studies using DSCs for various orodental and maxillofacial regenerative applications, including bone, periodontal, and endodontic regeneration. It also explores the utilization of DSCs in treating systemic conditions, exemplified by their application in managing conditions such as COVID-19 and osteoarthritis. The available evidence underscores the potential of DSCs and their secretome as efficacious tools in regenerative medicine for both dental and nondental clinical applications, supporting the continued promise of stem cell-based therapies. It is nevertheless evident that there are a number of important challenges that restrict the widespread utilization of DSCs, namely, difficulty in standardizing autologous preparations, insufficient cell surface marker characterization, high production costs, and regulatory compliance requirements. Further, the unique requirements of dental applications, especially complex structures such as the periodontium, where temporospatial control over the healing process is required, necessitate the combination of stem cells with appropriate scaffolds according to the principles of tissue engineering. There is currently insufficient evidence to support the clinical translation of DSCs into clinical practice, and phase 3 clinical trials with standardized protocols for cell sourcing, propagation, dosing, and delivery are required to move the field forward. In summary, this review provides a contemporary overview of the evolving landscape of stem cell therapy, offering insights into the latest developments and trends as well as the challenges that need to be addressed for the widespread application of DSC-based cell therapies.

Exosomes Derived from Rejuvenated Stem Cells Inactivate NLRP3 Inflammasome and Pyroptosis of Nucleus Pulposus Cells via the Transfer of Antioxidants.

Accumulating evidence supports the potential of exosomes as a promising therapeutic approach for intervertebral disc degeneration (IDD). Nevertheless, enhancing the efficiency of exosome treatment remains an urgent concern. This study investigated the impact of quercetin on the characteristics of mesenchymal stem cells (MSCs) and their released exosomes. Exosomes were obtained from quercetin pre-treated MSCs and quantified for the production based on nanoparticle tracking and western blot analysis. The molecules involved in the secretion and cargo sorting of exosomes were investigated using western blot and immunofluorescence analysis. Based on the in vitro biological analysis and in vivo histological analysis, the effects of exosomes derived from conventional or quercetin-treated MSCs on nucleus pulposus (NP) cells were compared. A significant enhancement in the production and transportation efficiency of exosomes was observed in quercetin-treated MSCs. Moreover, the exosomes derived from quercetin-treated MSCs exhibited a greater abundance of antioxidant proteins, specifically superoxide dismutase 1 (SOD1), which inhibit the activation of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome in NP cells. Through in vitro and in vivo experiments, it was elucidated that exosomes derived from quercetin-treated MSCs possessed enhanced anti-inflammatory and antioxidant properties. Collectively, our research underscores an optimized therapeutic strategy for IDD utilizing MSC-derived exosomes, thereby augmenting the efficacy of exosomes in intervertebral disc regeneration.

Antibacterial effects of human mesenchymal stem cells and their derivatives: a systematic review.

The growing problem of antimicrobial resistance (AMR) poses a significant challenge to public health; This is partly due to the lack of advancements in the development of novel antibiotics and the pressing need for alternative treatment options. Mesenchymal stem cells (MSC) possess secretory components that enhance the immune response and peptides that disrupt the bacteria constitution. The isolation of various human tissues has facilitated the investigation of the diverse potentials of MSC and their components. Further research is needed to fully understand the spectrum and efficacy of these elements and their differences. The primary aim of this study was to perform a thorough review of the current literature related to the antimicrobial properties of MSC and their associated components. The objective was to establish an insight into the results and effects of utilizing MSC in relation to bacterial colonization, and to present an overview of previously documented findings. This systematic literature review was conducted using the PubMed, Embase, and Web of Science databases. Data on the effect of MSC or their derivatives were measured by calculating the percentage of bacterial counts reduction after treatment with MSC in comparison to the control. A total of 3,911 articles were screened, and 31 eligible publications were selected for inclusion in the analysis. In the current systematic review, the majority of the experimental designs showed positive outcomes in terms of bacterial load reduction when MSC or their derivatives were used, with bone marrow being the most effective tissue. The rest of the findings exhibited heterogeneity in the spectrum of outcomes that could be attributed to the effects of using various tissues derived MSC in both in vivo and in vitro studies. The findings of our study indicate the potential antibacterial characteristics of MSC. The direct antimicrobial activity of these cells was demonstrated by our results, which quantitatively showed a decrease in bacterial growth after treatment with MSC. However, additional research is required to clarify the factors that determine the efficacy of their antimicrobial activity and their various components.

Anti-Inflammatory and Anti-(Lymph)angiogenic Properties of an ABCB5+ Limbal Mesenchymal Stem Cell Population.

Corneal transparency and avascularity are essential for vision. The avascular cornea transitions into the vascularized conjunctiva at the limbus. Here, we explore a limbal stromal cell sub-population that expresses ABCB5 and has mesenchymal stem cell characteristics. Human primary corneal stromal cells were enriched for ABCB5 by using FACS sorting. ABCB5+ cells expressed the MSC markers CD90, CD73, and CD105. ABCB5+ but not ABCB5- cells from the same donor displayed evidence of pluripotency with a significantly higher colony-forming efficiency and the ability of trilineage differentiation (osteogenic, adipogenic, and chondrogenic). The ABCB5+ cell secretome demonstrated lower levels of the pro-inflammatory protein MIF (macrophage migration inhibitory factor) as well as of the pro-(lymph)angiogenic growth factors VEGFA and VEGFC, which correlated with reduced proliferation of Jurkat cells co-cultured with ABCB5+ cells and decreased proliferation of blood and lymphatic endothelial cells cultured in ABCB5+ cell-conditioned media. These data support the hypothesis that ABCB5+ limbal stromal cells are a putative MSC population with potential anti-inflammatory and anti-(lymph)angiogenic effects. The therapeutic modulation of ABCB5+ limbal stromal cells may prevent cornea neovascularization and inflammation and, if transplanted to other sites in the body, provide similar protective properties to other tissues.

Potential Mechanism and Perspectives of Mesenchymal Stem Cell Therapy for Ischemic Stroke: A Review.

Mesenchymal stem cells (MSCs), as a stem cell type with multiple differentiation potentials and immune regulatory abilities, have shown broad prospects in the treatment of ischemic stroke in recent years. The main characteristics of MSCs include their self-renewal ability, differentiation potential for different types of cells, and the ability to secrete various bioactive factors such as cytokines, chemokines, and growth factors, which play a key role in tissue repair and regeneration. In the treatment of ischemic stroke, MSCs exert therapeutic effects through various mechanisms, including promoting vascular regeneration of damaged brain tissue, reducing inflammatory responses, and protecting neurons from damage caused by apoptosis. Research have shown that MSCs can promote the repair of ischemic areas by releasing neurotrophic factors and angiogenic factors, while inhibiting immune responses triggered by ischemia, thereby improving neurological function. With the in-depth study of its biological mechanism, MSCs have gradually shown good safety and effectiveness in clinical applications. Therefore, fully exploring and utilizing the potential of MSCs in the treatment of ischemic stroke may provide new ideas and solutions for future neural repair and regenerative medicine.

Youthful small extracellular vesicles restore the function and reparative capacity of inflammatory-impaired periodontal ligament stem cells via delivering protein biglycan for bone regeneration

Regenerating inflamed bone defects represents a severe clinical challenge due to the undesirable inflammatory microenvironment. The inflammatory stimulus poses a weighty threat to the regenerative capacity of endogenously derived mesenchymal stem cells (MSCs), which are mainly responsible for osteogenic differentiation, thereby resulting in compromised endogenous bone formation. Consequently, alleviating the biological characteristics of inflammatory-impaired MSCs is crucial for promoting inflamed bone regeneration. Nano-sized small extracellular vesicles (sEVs) have emerged as promising therapeutic tools to orchestrate MSCs fate due to their intrinsic biocompatibility and encapsulated bioactive contents. In the present study, we extracted sEVs from youthful and adult dental pulp MSCs and explored their ability to recover inflammation-compromised periodontal ligament stem cells (IPDLSCs). The results indicated that both types of sEVs were capable of facilitating IPDLSCs osteogenesis. However, young sEVs exhibited a more robust potential at a lower concentration compared to adult sEVs. Mechanically, young sEVs enhanced the expression of bone morphogenetic protein 4 (BMP4) via delivering the protein Biglycan, which correspondingly promoted the osteogenic capability of IPDLSCs. Collectively, our findings emphasized that young sEVs hold enormous potential to rescue the inherent function and regenerative competence of inflammation-impaired MSCs, shedding light on their promising therapeutic prospects for infected bone regeneration.

A Comparative Analysis of the Age-dependent Features of Mesenchymal Stem Cells from Buffalo Adipose Tissue

Background: Mesenchymal stem cells are a potential candidate for regenerative medicine. Many factors may influence the physiological characteristics of stem cells that may lead to the alteration in their potential. Methods: The impact of age on mesenchymal stem cell characteristics was investigated in older buffaloes (aged over 10 years) and compared to younger counterparts (aged less than 2 years). Following isolation through enzymatic digestion, the mesenchymal stem cells were cultured in DMEM containing 12.5% FBS and antibiotics. Different variables indicating stem cell characteristics were evaluated at subsequent cultures. Result: The results revealed both groups displayed positive staining for alkaline phosphatase (AP) and expressed stem cell markers, including CD73, CD105 and OCT4, while remain negative for CD34. Furthermore, both sets of stem cells demonstrated the ability to differentiate into adipogenic, osteogenicand chondrogenic lineages. There were no notable variations observed between the two groups in terms of the cell yield, percentages of senescent cells, necrotic cells, dead cells and the apoptotic index. Expression of the P53 gene in RT-PCR amplicon in both groups confirms that stem cells are dividing normally as healthy cells and not tumor cells. Consequently, it was concluded from the present investigation that the age of the animal does not influence the characteristics of mesenchymal stem cells derived from adipose tissue. Thus, the stem cells derived from older and younger buffaloes are suited equally as a cell source for regenerative therapeutics.

Impact of Strontium, Magnesium, and Zinc Ions on the In Vitro Osteogenesis of Maxillary Sinus Membrane Stem Cells.

Human Maxillary Sinus Membrane Stem Cells (hMSMSCs) contribute significantly to bone formation following maxillary sinus floor augmentation (MSFA). The biological behavior of mesenchymal stem cells is notably influenced by varying concentrations of magnesium (Mg2+), strontium (Sr2+), and zinc (Zn2+) ions; however, their specific effects on hMSMSCs have not been comprehensively studied. We isolated hMSMSCs and identified their mesenchymal stem cell characteristics by flow cytometry and multilineage differentiation experiments. Subsequently, the hMSMSCs were cultured in media containing different concentrations of these metal ions. The proliferation and viability of hMSMSCs were assessed using CCK-8 and Calcein AM/PI staining. After osteogenic induction, cells were evaluated for alkaline phosphatase (ALP) activity, ALP staining, and Alizarin Red staining. Additionally, qRT-PCR was used to detect differences in osteogenic gene expression, and immunofluorescence staining was used to observe variations in OCN protein levels. The results indicated that 1 mM Mg2+, 0.01 mM Sr2+, and 0.001 mM Zn2+ significantly improved the proliferation and activity of hMSMSCs. These concentrations also notably enhanced ALP secretion, increased bone-related gene expression, and augmented osteocalcin expression and formation of extracellular calcium nodules, thereby improving osteogenic differentiation. However, higher concentrations of Mg2+, Sr2+, and Zn2+ decreased cell viability and osteogenic differentiation. Mg2+, Sr2+, and Zn2+ promote osteogenic differentiation and proliferation of hMSMSCs in a concentration-dependent manner, indicating that the type and concentration of ions in the extracellular environment can significantly alter hMSMSCs behavior, which is a crucial consideration for material design in maxillary sinus elevation applications.

Adipose-derived Mesenchymal Stem Cell Transplantation Improves Ovarian Function and Oocyte Quality in Aged Mice.

Age-related decline in the number of ovulations and ovum quality are major causes of female infertility, and stem cells have been reported to be effective in tissue regeneration. However, current therapeutic modalities are inadequate. This study investigated the effects of adipose-derived mesenchymal stem cells (ASCs) on ovarian functions in aged mice. Following the characterization of ASCs using flow cytometry, the effects of ASCs on the number of ovulations, fertilization rate, and blastocyst-formation rate were investigated. In addition, the number of ovarian follicles and serum anti-Müllerian hormone (AMH) levels were examined. ASCs marked with Kusabira Orange were used to examine the location after cell administration. The quality of ovulated oocytes was analyzed using next-generation RNA sequencing. ASCs showed characteristics of mesenchymal stem cells and were distributed to various organs, including the ovarian stroma. The transplantation resulted in increased number of oocytes and ovulation in the ovaries and increased AMH values. Genetic analysis revealed improved oocyte quality and increased fertilization and blastocyst-formation rates. ASC therapy may be effective in improving fertility in older women.

Research Progress on Cardiac Tissue Construction of Mesenchymal Stem Cells for Myocardial Infarction.

Heart failure is still the main complication affecting the prognosis of acute myocardial infarction (AMI), and mesenchymal stem cells (MSCs) are an effective treatment to replace necrotic myocardium and improve cardiac functioning. However, the transplant survival rate of MSCs still presents challenges. In this review, the biological characteristics of MSCs, the progress of mechanism research in the treatment of myocardial infarction, and the advances in improving the transplant survival rate of MSCs in the replacement of necrotic myocardial infarction are systematically described. From a basic to advanced clinical research, MSC transplants have evolved from a pure injection, an exosome injection, the genetic modification of MSCs prior to injection to the cardiac tissue engineering of MSC patch grafting. This study shows that MSCs have wide clinical applications in the treatment of AMI, suggesting improved myocardial tissue creation. A broader clinical application prospect will be explored and developed to improve the survival rate of MSC transplants and myocardial vascularization.

Investigating the differential therapeutic efficacy and mechanisms of human umbilical cord mesenchymal stem cells at various passages in osteoarthritis treatment

This study aimed to assess the clinical efficacy of umbilical cord mesenchymal stem cells (hUC-MSCs) from different passages (P3, P8, and P13) in the treatment of knee osteoarthritis (OA) and explore the underlying mechanisms. The hUC-MSCs from each passage were characterized and evaluated for their stemness, migration, proliferation, and marker expression. Rats with OA were treated with hUC-MSCs from each passage, and the therapeutic effects were assessed based on knee swelling, discomfort, and pathological examination of the knee joint. Co-culture experiments were conducted to examine the ability of hUC-MSCs to stimulate type II collagen synthesis and inhibit MMP13 expression in chondrocytes. Telomere length and telomerase activity of hUC-MSCs from each passage were measured to investigate the reasons for the observed differences in clinical efficacy. The results revealed that P3 and P8 hUC-MSCs exhibited superior osteogenic and chondrogenic differentiation potential compared to P13, while P13 demonstrated stronger adipogenic differentiation. The wound healing rate was significantly higher in the P3 and P8 groups compared to P13. All hUC-MSC groups expressed high levels of CD90 and CD105, indicating their mesenchymal stem cell characteristics, while CD31 and CD45 were not expressed. CD105 expression was significantly reduced in the P13 group. In the treatment of rat osteoarthritis, there were no significant differences in knee swelling, discomfort, Mankin scores, and pathological findings between P3 and P8 hUC-MSC treatments. However, there was a significant difference between the 8th and 13th passages. Co-culture experiments showed that hUC-MSCs from P3 and P8 enhanced type II collagen synthesis and reduced MMP13 expression in chondrocytes. Although no significant difference was observed between the P3 and P8 groups, a significant difference was found between the P13 and P8 groups. Telomere length analysis revealed that P13 samples had significantly shorter telomeres compared to both P3 and P8. The telomerase activity was positive in P3 and P8 hUC-MSCs, indicating no significant difference between these passages, while it was negative in P13 hUC-MSCs. In conclusion, P3 and P8 hUC-MSCs exhibited superior therapeutic potential for knee osteoarthritis compared to P13, possibly due to their enhanced differentiation capacity and telomerase activity.

Therapeutic Potential of Olfactory Ensheathing Cells and Adipose-Derived Stem Cells in Osteoarthritis: Insights from Preclinical Studies.

Olfactory-ensheathing cells (OECs) are known for their role in neuronal regeneration and potential to promote tissue repair. Adipose-derived stem cells (ADSCs), characterized by mesenchymal stem cell (MSC) traits, display a fibroblast-like morphology and express MSC surface markers, making them suitable for regenerative therapies for osteoarthritis (OA). In this study, OECs and ADSCs were derived from tissues and characterized for their morphology, surface marker expression, and differentiation capabilities. Collagenase-induced OA was created in 10-week-old C57BL/6 mice, followed by intra-articular injections of ADSCs (1 × 105), OECs (1 × 105), or a higher dose of OECs (5 × 105). Therapeutic efficacy was evaluated using rotarod performance tests, MRI, histology, and immunohistochemistry. Both cell types exhibited typical MSC characteristics and successfully differentiated into adipocytes, osteoblasts, and chondrocytes, confirmed by gene expression and staining. Transplantation significantly improved rotarod performance and preserved cartilage integrity, as seen in MRI and histology, with reduced cartilage destruction and increased chondrocytes. Immunohistochemistry showed elevated type II collagen and aggrecan in treated joints, indicating hyaline cartilage formation, and reduced MMP13 and IL-1β expression, suggesting decreased inflammation and catabolic activity. These findings highlight the regenerative potential of OECs and ADSCs in treating OA by preserving cartilage, promoting chondrocyte proliferation, and reducing inflammation. Further research is needed to optimize delivery methods and evaluate long-term clinical outcomes.

P-786 Mesenchymal stem cells as a potential source of ovarian theca interna cell differentiation

Abstract Study question Are mesenchymal stem cells (MSCs) the cell source of origin during the differentiation of ovarian stromal cells into theca interna cells (TICs)? Summary answer MSC-like cells were observed during in vitro TIC differentiation, particularly on day 2, suggesting their potential role in the origin of TICs. What is known already Folliculogenesis is the process during which a follicle develops from its primordial towards its antral stage. Follicles in the antral stage consist of an oocyte, granulosa and theca cells. While the oocyte is surrounded by granulosa cells in the primordial stage, theca cells differentiate from their precursor cell from the secondary stage onwards. Recent studies identified the existence of theca stem cells (TSCs) in both humans and animals. These TSCs express both platelet-derived growth factor receptor (PDGFR) and nerve growth factor receptor (NGFR), and demonstrate the ability to differentiate into mesenchymal cell lineages, resembling characteristics of MSCs. Study design, size, duration Ovarian stromal cells were isolated from cryopreserved cortex fragments, and cultured in vitro for 13 days, using cell media enriched with various growth factors and hormones, as previously established by our group. Flow cytometry, immunocytochemistry, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and enzyme-linked immunosorbent assay (ELISA) were employed to analyze the cells and their media at days 0, 2, 8 and 13. Participants/materials, setting, methods Whole ovaries from three postmenopausal organ donors were obtained (50, 54, and 64 years) and the cortex was cryopreserved in small 5x5 fragments prior to the isolation and differentiation into TICs. Main results and the role of chance Immunocytochemistry results showed an increase in the proportion of cells positive for TIC markers from day 0 to day 8 (12.13 ± 2.11% vs. 57.73 ± 49.99%), while the proportion of MSC-like cell markers was increased significantly from day 0 to day 2 (4.54 ± 1.71% vs. 57.34 ± 18.05%). This TIC proportion aligns with the rising androstenedione levels from day 2 to day 13 (81.31 ± 25.09 pg/ml vs. 384.29 ± 245.82 pg/ml). Flow cytometry analysis identified a CD73+ CD90+ CD105+ CD34- CD45- HLA-DR- cell population, expanding from less than 1% on day 0, to 15.30 ± 7.9% on day 2. A CD13+ cell population and its corresponding gene expression increased significantly from the beginning towards the end of the culture (13.52 ± 7.9% vs. 84.13 ± 11.08, and 1.38 ± 0.97 vs. 285.80 ± 27.43, flow cytometry and gene expression analysis respectively). Moreover, NGFR and PDGFRA expression was induced on day 0 and day 2, respectively, compared to day 13 (1.12 ± 0.60 vs. 0.08 ± 0.08, and 2.03 ± 1.11 vs. 0.24 ± 0.14). In conclusion, our study provides valuable insights into the differentiation potential of TICs, suggesting a possible origin from MSCs. Limitations, reasons for caution Due to the limited accessibility of a large quantity of human ovarian tissue from postmenopausal women, this study is restricted to three biological replicates. When examining statistical differences, it is crucial to bear in mind the considerable biological variabilities that exist among humans. Wider implications of the findings Characterizing the origin of TICs will allow for a comprehensive study of TICs, leading to a broader knowledge of these cells. The in vitro differentiation to TICs from easily accessible cells, like MSCs, holds potential significance in toxicity studies and investigating TIC-related disorders, such as polycystic ovary syndrome (PCOS). Trial registration number not applicable

Restoration of functional endometrium in an intrauterine adhesion rat model with endometrial stromal cells transplantation

BackgroundIntrauterine adhesion (IUA) as a prevalent gynecological disease is developed from infection or trauma. However, therapeutic strategies to repair damaged endometrium are relatively limited. Emerging studies have shed light on the crucial role of endometrial stromal cells (EnSCs) in the process of uterine endometrial regeneration. EnSCs isolated from the uterine endometrium have similar characteristics to mesenchymal stem cells (MSCs). However, it is still unknown whether EnSCs could be used as donor cells to treat IUA. The aim of this study was to evaluate the potential efficacy of EnSCs in treating rat IUA.MethodsHuman EnSCs were isolated from the endometrial tissue of healthy female donors and subjected to extensive expansion and culture in vitro. Immunofluorescence, flow cytometry, cell proliferation assay, trilineage differentiation experiment, and decidualization assay were used to characterize the biological properties of EnSCs. We evaluated the immunoregulatory potential of EnSCs by analyzing their secreted cytokines and conducting bulk RNA sequencing after IFN-γ treatment. After EnSCs were transplanted into the uterine muscle layer in IUA rats, their therapeutic effects and underlying mechanisms were analyzed using histological analysis, Q-PCR, fertility and pregnancy outcome assay, and transcriptome analysis.ResultsWe successfully isolated EnSCs from the endometrium of human donors and largely expanded in vitro. EnSCs exhibited characteristics of mesenchymal stem cells and retained responsiveness to sex hormones. Following IFN-γ stimulation, EnSCs upregulated the anti-inflammatory cytokines and activated immunosuppressive molecules. Xenogeneic transplantation of EnSCs successfully repaired injured endometrium and significantly restored the pregnancy rate in IUA rats. Mechanistically, the therapeutic effects of EnSCs on IUA endometrium functioned through anti-inflammation, anti-fibrosis and the secretion of regeneration factor.ConclusionsDue to their large expansion ability, immunoregulatory properties, and great potential in treating IUA, EnSCs, as a valuable source of donor cells, could offer a potential treatment avenue for injury-induced IUA.

Distinct biological characteristics of mesenchymal stem cells separated from different components of human placenta

Mesenchymal stem cells (MSCs) have tremendous potential in cell therapy and regenerative medicine. The placenta-derived MSCs (PMSCs) are becoming favorable sources as they are ethically preferable and rich in MSCs. Although several subgroups of PMSCs have been identified from human term placenta, optimal sources for specific clinical applications remain to be elucidated. This study aimed to isolate MSCs from various components of the placenta, and compare their biological characteristics, including morphology, proliferation, immunophenotype, differentiation potential, growth factor and cytokine secretion, and immunomodulatory properties. Finally, four distinct groups of PMSCs were isolated from the placenta: amniotic membrane-derived MSCs (AM-MSCs), chorionic membrane-derived MSCs (CM-MSCs), chorionic plate-derived MSCs (CP-MSCs), and chorionic villi-derived MSCs (CV-MSCs). The results showed that CV-MSCs had good proliferation ability, and were easier to induce osteogenic and chondrogenic differentiation; CP-MSCs exhibited the strongest inhibitory effect on the proliferation of activated T cells, secreted high levels of EGF and IL-6, and could well differentiate into osteoblasts, adipocytes, and chondroblasts; AM-MSCs showed good growth dynamics in the early generations, were able to grow at high density, and tended to induce differentiation into osteogenic and neural lineages. These findings may provide novel evidence for the selection of seed cells in clinical application.

Therapeutic potential of mesenchymal stem cell-derived exosomes in skeletal diseases.

Skeletal diseases impose a considerable burden on society. The clinical and tissue-engineering therapies applied to alleviate such diseases frequently result in complications and are inadequately effective. Research has shifted from conventional therapies based on mesenchymal stem cells (MSCs) to exosomes derived from MSCs. Exosomes are natural nanocarriers of endogenous DNA, RNA, proteins, and lipids and have a low immune clearance rate and good barrier penetration and allow targeted delivery of therapeutics. MSC-derived exosomes (MSC-exosomes) have the characteristics of both MSCs and exosomes, and so they can have both immunosuppressive and tissue-regenerative effects. Despite advances in our knowledge of MSC-exosomes, their regulatory mechanisms and functionalities are unclear. Here we review the therapeutic potential of MSC-exosomes for skeletal diseases.

Harnessing three-dimensional porous chitosan microsphere embedded with adipose-derived stem cells to promote nerve regeneration

BackgroundNerve guide conduits are a promising strategy for reconstructing peripheral nerve defects. Improving the survival rate of seed cells in nerve conduits is still a challenge and microcarriers are an excellent three-dimensional (3D) culture scaffold. Here, we investigate the effect of the 3D culture of microcarriers on the biological characteristics of adipose mesenchymal stem cells (ADSCs) and to evaluate the efficacy of chitosan nerve conduits filled with microcarriers loaded with ADSCs in repairing nerve defects.MethodsIn vitro, we prepared porous chitosan microspheres by a modified emulsion cross-linking method for loading ADSCs and evaluated the growth status and function of ADSCs. In vivo, ADSCs-loaded microcarriers were injected into chitosan nerve conduits to repair a 12 mm sciatic nerve defect in rats.ResultsCompared to the conventional two-dimensional (2D) culture, the prepared microcarriers were more conducive to the proliferation, migration, and secretion of trophic factors of ADSCs. In addition, gait analysis, neuro-electrophysiology, and histological evaluation of nerves and muscles showed that the ADSC microcarrier-loaded nerve conduits were more effective in improving nerve regeneration.ConclusionsThe ADSCs-loaded chitosan porous microcarrier prepared in this study has a high cell engraftment rate and good potential for peripheral nerve repair.Graphical