Menstrual Blood-derived Mesenchymal Stem Cells Research Articles

Human menstrual blood-derived stem cells mitigate bleomycin-induced pulmonary fibrosis through anti-apoptosis and anti-inflammatory effects

BackgroundIdiopathic pulmonary fibrosis is a kind of diffuse interstitial lung disease, the pathogenesis of which is unclear, and there is currently a lack of good treatment to improve the survival rate. Human menstrual blood-derived mesenchymal stem cells (MenSCs) have shown great potential in regenerative medicine. This study aimed to explore the therapeutic potential of MenSCs for bleomycin-induced pulmonary fibrosis.MethodsWe investigated the transplantation of MenSCs in a pulmonary fibrosis mouse model induced by BLM. Mouse was divided into three groups: control group, BLM group, MenSC group. Twenty-one days after MenSC transplantation, we examined collagen content, pathological, fibrosis area in the lung tissue, and the level of inflammatory factors of serum. RNA sequence was used to examine the differential expressed gene between three groups. Transwell coculture experiments were further used to examine the function of MenSCs to MLE-12 cells and mouse lung fibroblasts (MLFs) in vitro.ResultsWe observed that transplantation of MenSCs significantly improves pulmonary fibrosis mouse through evaluations of pathological lesions, collagen deposition, and inflammation. Transwell coculturing experiments showed that MenSCs suppress the proliferation and the differentiation of MLFs and inhibit the apoptosis of MLE-12 cells. Furthermore, antibody array results demonstrated that MenSCs inhibit the apoptosis of MLE-12 cells by suppressing the expression of inflammatory-related cytokines, including RANTES, Eotaxin, GM-CSF, MIP-1γ, MCP-5, CCL1, and GITR.ConclusionsCollectively, our results suggested MenSCs have a great potential in the treatment of pulmonary fibrosis, and cytokines revealed in antibody array are expected to become the target of future therapy of MenSCs in clinical treatment of pulmonary fibrosis.

Osteogenic induction of menstrual blood mesenchymal stem cell by different Ferula species extracts.

Objective: Ferula spp. have many applications in complementary medicine and are recognized as the most important sources of natural products for bone health and regeneration especially in postmenopausal women. Therefore, the aim of this study was to investigate the effects of the extracts from three Ferula species on proliferation and osteogenesis potential of human menstrual blood-derived mesenchymal stem cells (MenSCs). Materials and Methods: The possible cytotoxic activity of three members of Ferula spp. (at concentrations of 5 to 100 μg/ml) was determined using MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) assay. Alkaline phosphatase (ALP) activity assay, Alizarin Red-S staining, and the expression analysis of an osteoblastic gene were performed to evaluate osteogenic differentiation potential. Results: The extracts of F. flabelliloba and F. szowitsiana decreased the viability and growth of MenSCs while F. foetida increased the proliferation of cells after 72 hr incubation. Treatment of MenSCs with selected plant extracts revealed that F. foetida and F. szowitsiana could enhance the osteogenic potential of MenSCs in terms of ALP activity. The Runx-2 expression in the presence of F. foetida was significantly greater than observed following treatment with 17β-estradiol (as positive control). Conclusion: The results of this study suggest that F. foetida and F. szowitsiana may have therapeutic values as a nutraceutical with respect to their considerable influence on osteogenic potential of mesenchymal stem cells.

Menstrual Blood-Derived Mesenchymal Stem Cells: Women's Attitudes, Willingness, and Barriers to Donation of Menstrual Blood

Background: Menstrual blood contains mesenchymal stem cells (MenSC), considered a potential "off-the-shelf" treatment for a range of diseases and medical conditions. Samples of menstrual blood can be collected painlessly, inexpensively, and as frequently as every month for cell therapy. While there has been considerable previous research into the clinical advantages of MenSC, there is currently little understanding of potential donors' attitudes regarding menstrual blood donation and MenSC. Methods: One hundred women 18 years of age or over were surveyed to understand attitudes and potential barriers to menstrual blood donation. The questionnaire assessed participant age and brief medical history (giving birth, donating blood, donating stem cells), menstrual experience (period rating, preferred menstrual hygiene products), and whether participants would donate MenSC or accept MenSC therapy. Results: MenSC was met with a generally positive response, with 78% of menstruating women willing to donate menstrual blood. No significant relationship was recognized between willingness to donate menstrual blood with age, history of childbirth or blood donation, menstruation perception, and preferred menstrual hygiene product. Women rated their period experience better after being made aware of the ability to donate menstrual blood, meaning MenSC therapy can be beneficial for donors as well as patients. Conclusions: Considering women's attitudes to MenSC and donation of menstrual blood, the future of MenSC therapy is positive; women are generally willing to donate menstrual blood, independent of age, perception of periods, and history of childbirth and blood donation.

Menstrual blood derived mesenchymal stem cells combined with Bushen Tiaochong recipe improved chemotherapy-induced premature ovarian failure in mice by inhibiting GADD45b expression in the cell cycle pathway

BackgroundTo investigate the therapeutic effects of menstrual blood derived mesenchymal stem cells (MB-MSCs) combined with Bushen Tiaochong recipe (BSTCR) on epirubicin induced premature ovarian failure (POF) in mice.MethodsTwenty-four female C57BL/6 mice of 6–8 weeks were intraperitoneally injected with epirubicin to induce POF, and then they were randomized into 4 groups of 6 mice each and treated with PBS, MB-MSCs, BSTCR, and MB-MSCs combined with BSTCR, respectively. Six mice of the same age were used as controls. Vaginal smear, TUNEL and hematoxylin-eosin staining were to observe estrous cycles, ovarian cell apoptosis and follicles. Enzyme-linked immunosorbent analysis determined serum estradiol, follicle-stimulating hormone (FSH) and anti-Müllerian hormone (AMH) levels. RT-qPCR and Western Blot analysis were to determine GADD45b, CyclinB1, CDC2 and pCDC2 expressions.ResultsEpirubicin treatment resulted in a decrease in the number of primordial, primary, secondary and antral follicles, an increase in the number of atretic follicles and ovarian cell apoptosis, a decrease in estradiol and AMH levels, an increase in FSH levels, and estrous cycle arrest. However, MB-MSCs combined with BSTCR rescued epirubicin induced POF through down-regulating GADD45b and pCDC2 expressions, and up-regulating CyclinB1 and CDC2 expressions. The combined treatment showed better therapeutic efficacy than BSTCR or MB-MSCs alone.ConclusionsMB-MSCs combined with BSTCR improved the ovarian function of epirubicin induced POF mice, which might be related to the inhibition of GADD45b expression and the promotion of CyclinB1 and CDC2 expressions. The combined treatment had better therapeutic efficacy than BSTCR or MB-MSCs alone.

Enhanced antitumor efficacy of an oncolytic adenovirus armed with an EGFR-targeted BiTE using menstrual blood-derived mesenchymal stem cells as carriers.

Poor tumor targeting of oncolytic adenoviruses (OAdv) after systemic administration is considered a major limitation for virotherapy of disseminated cancers. The benefit of using mesenchymal stem cells as cell carriers for OAdv tumor targeting is currently evaluated not only in preclinical models but also in clinical trials. In this context, we have previously demonstrated the enhanced antitumor efficacy of OAdv-loaded menstrual blood-derived mesenchymal stem cells (MenSCs). However, although significant, the antitumor efficacy obtained was modest, and we hypothesized that a greater antitumor efficacy could be obtained arming the OAdv with a therapeutic transgene. Here we show that combining MenSCs with ICOVIR15-cBiTE, an OAdv expressing an epidermal growth factor receptor (EGFR)-targeting bispecific T-cell engager (cBiTE), enhances the antitumor efficacy compared to MenSCs loaded with the unarmed virus ICOVIR15. We found that MenSCs properly produce cBiTE after viral infection leading to a greater antitumor potency both in vitro and in vivo. These findings indicate the mutual benefit of combining MenSCs and armed OAdv and support the combination of ICOVIR15-cBiTE and MenSCs as a cancer treatment.

Menstrual Blood-Derived Stem Cells as Delivery Vehicles for Oncolytic Adenovirus Virotherapy for Colorectal Cancer

Oncolytic adenoviruses (Ads) have potential applications in cancer therapy due to their ability to replicate and induce tumor cell death. However, their clinical application has been limited by the lack of efficient cell-based delivery systems that can provide protection from immune attack and prevent virus clearance by neutralizing antibodies. We previously demonstrated that menstrual blood-derived mesenchymal stem cells (MenSCs) can specifically target tumor cells and serve as a novel drug delivery platform. We engineered CRAd5/F11 chimeric oncolytic Ads that can infect MenSCs and preserve their tumor targeting ability in vitro. MenSCs loaded with these Ads were transplanted in a mouse tumor model. We found that a large number of the CRAd5/F11 viruses were accumulated in tumor site and mediated marked inhibitory effects against colorectal cancer (CRC). Thus, we concluded that MenSC-cloaked oncolytic Ads hold great potential as a novel virus-delivery platform for the therapy of various cancers, including CRC.

Potential of stem cell-derived exosomes to regenerate β islets through Pdx-1 dependent mechanism in a rat model of type 1 diabetes.

Type 1 diabetes, has been recognized as an autoimmune disease. Like other immunological conditions, regulation of immune response is a key strategy to control the autoimmunity in diabetic patients. Mesenchymal stem cells have been shown to have a distinct potential in modulating the immune reactions. However, treatment with stem cells is combined with concerns about safety issues. To overcome these concerns, in this study, we have utilized the regenerative potential of exosomes isolated from menstrual blood-derived mesenchymal stem cells to restore the β-cell mass and insulin production in type 1 diabetes. Exosomes are nanovesicles containing various cargos involved in cellular communications. Streptozotocin was used to induce islet destruction and diabetes in male Wistar rats. Then, exosomes were intravenously injected into animals at different time points and in a single or repeated therapeutic doses. After about 6 weeks, animals were euthanized and the pancreas was analyzed for the presence of the regenerated β islets as well as the insulin secretion. The non-fasting blood glucose and the serum insulin level were also monitored during the study. Our results represented that menstrual blood-derived mesenchymal stem cell-derived exosomes enhance the β-cell mass and insulin production in the pancreas of diabetic animals that received repeated doses of exosomes. Immunohistochemistry analysis also confirmed the presence of insulin in the islets of treated animals. Further investigations proposed that exosomes induce the islet regeneration through pancreatic and duodenal homeobox 1 pathway. The exosome tracking also revealed the homing of injected exosomes to the pancreas.

Promising effects of exosomes isolated from menstrual blood‐derived mesenchymal stem cell on wound‐healing process in diabetic mouse model

Wound healing is a complicated process that contains a number of overlapping and consecutive phases, disruption in each of which can cause chronic nonhealing wounds. In the current study, we investigated the effects of exosomes as paracrine factors released from menstrual blood-derived mesenchymal stem cells (MenSCs) on wound-healing process in diabetic mice. The exosomes were isolated from MenSCs conditioned media using ultracentrifugation and were characterized by scanning electron microscope and western blotting assay. A full thickness excisional wound was created on the dorsal skin of each streptozotocin-induced diabetic mouse. The mice were divided into three groups as follows: phosphate buffered saline, exosomes, and MenSC groups. We found that MenSC-derived exosomes can resolve inflammation via induced M1-M2 macrophage polarization. It was observed that exosomes enhance neoangiogenesis through vascular endothelial growth factor A upregulation. Re-epithelialization accelerated in the exosome-treated mice, most likely through NF-κB p65 subunit upregulation and activation of the NF-κB signaling pathway. The results demonstrated that exosomes possibly cause less scar formation through decreased Col1:Col3 ratio. These notable results showed that the MenSC-derived exosomes effectively ameliorated cutaneous nonhealing wounds. We suggest that exosomes can be employed in regenerative medicine for skin repair in difficult-to-heal conditions such as diabetic foot ulcer.

Human menstrual blood-derived stem cells protect H9c2 cells against hydrogen peroxide-associated apoptosis.

Human menstrual blood-derived mesenchymal stem cells (MenSCs) hold great promise for regenerative medicine. Here, H2O2-associated damage in H9c2 cells was employed as an in vitro ischemia-reperfusion model, and the transwell system was used to explore the beneficial effects of MenSCs on the H2O2-induced damage of myocardial H9c2 cells. H2O2 treatment resulted in decreased viability and migration rate, with increased apoptosis levels in cells. By contrast, upon co-culture with MenSCs, H9c2 cell viability and migration were increased, whereas the apoptotic rate decreased. Additionally, western blot and qRT-PCR showed that MenSCs mediated the anti-apoptotic role by downregulating the pro-apoptotic genes Bax and caspase-3, while upregulating the anti-apoptotic effector Bcl-2. Furthermore, co-culture with MenSCs resulted in elevated expression of N-cadherin after H2O2 treatment. These findings indicate that MenSCs protect H9c2 cells against H2O2-associated programmed cell death and would help develop therapeutic tools for cardiomyocyte apoptosis associated with oxidative stress.

The Potential of Menstrual Blood-Derived Mesenchymal Stem Cells for Cartilage Repair and Regeneration: Novel Aspects.

Menstrual blood is a unique body fluid that contains mesenchymal stem cells (MSCs). These cells have attracted a great deal of attention due to their exceptional advantages including easy access and frequently accessible sample source and no need for complex ethical and surgical interventions, as compared to other tissues. Menstrual blood-derived MSCs possess all the major stem cell properties and even have a greater proliferation and differentiation potential as compared to bone marrow-derived MSCs, making them a perspective tool in a further clinical practice. Although the potential of menstrual blood stem cells to differentiate into a large variety of tissue cells has been studied in many studies, their chondrogenic properties have not been extensively explored and investigated. Articular cartilage is susceptible to traumas and degenerative diseases, such as osteoarthritis, and has poor self-regeneration capacity and therefore requires more effective therapeutic technique. MSCs seem promising candidates for cartilage regeneration; however, no clinically effective stem cell-based repair method has yet emerged. This chapter focuses on studies in the field of menstrual blood-derived MSCs and their chondrogenic differentiation potential and suitability for application in cartilage regeneration. Although a very limited number of studies have been made in this field thus far, these cells might emerge as an efficient and easily accessible source of multipotent cells for cartilage engineering and cell-based chondroprotective therapy.

Human menstrual blood-derived stem cells promote functional recovery in a rat spinal cord hemisection model

Spinal cord injury (SCI) is associated with a dismal prognosis including severe voluntary motor and sensory deficits in the presence of the current therapies, thus new and efficient treatment strategies are desperately required. Along with several advantages, such as easy accessibility, high-yield, potential of enormous proliferation, menstrual blood-derived mesenchymal stem cells (MenSCs) have been proposed as a promising strategy in regeneration medicine. In this study, the MenSCs were transplanted into incomplete thoracic (T10) spinal cord injury (SCI) rats, all rats were sacrificed at 7, 14, and 28 days after surgery. Based on the results, we found that MenSCs transplantation improved the hind limb motor function. Besides, H&E staining showed that MenSCs treatment markedly reduced cavity formation in the lesion site. Furthermore, treatment by MenSCs showed more MAP2-positive mature neurons, as well as axonal regeneration manifested by NF-200 and less expression of chondroitin sulfate proteoglycans (CSPGs) than the non-treatment in the lesion site. Additionally, immunofluorescence, Western blot, and qRT-PCR methods showed that levels of brain-derived neurotrophic factor (BDNF) were significantly higher in the injured spinal cord after implantation of MenSCs. Results of qRT-PCR indicated that inflammatory factors, including TNF-α and IL-1β were inhibited after MenSCs transplantation. The improved motor function of hind limb and the increased cell body area of motor neurons were suppressed by blocking of the BDNF-TrkB signaling. It was eventually revealed that MenSCs implantation had beneficial therapeutic effects on the rehabilitation of the rat spinal cord hemisection model, mainly by enhancing the expression of BDNF. MenSCs transplantation may provide a novel therapeutic strategy for patients with SCI in the future.

Comparative Effects of Umbilical Cord- and Menstrual Blood-Derived MSCs in Repairing Acute Lung Injury.

Mesenchymal stem cells (MSCs) can effectively relieve acute lung injury (ALI) in several in vivo models. However, the underlying mechanisms and optimal sources of MSCs are unclear. In the present study, we investigated the effects of umbilical cord- (UC-) and menstrual blood- (MB-) derived MSCs on ALI. MSCs were transplanted into a lipopolysaccharide-induced ALI mouse model, and the therapeutic effects were determined by histological, cellular, and biochemical analyses. Our results showed that both UCMSC and MBMSC transplantation inhibited the inflammatory response and promoted lung tissue repair. UCMSC treatment resulted in reduced damage and inflammation in the lung tissue and enhanced protection of lung function. Furthermore, we found that UCMSCs secreted higher levels of anti-inflammatory cytokines (interleukin-10 and keratinocyte growth factor) in ALI-related conditions, which may be due to the greater therapeutic capacity of UCMSCs compared with MBMSCs. These findings suggest that MSCs protected the lipopolysaccharide-induced ALI model by regulating inflammation, most likely via paracrine factors. Moreover, MSCs derived from the UC may be a promising alternative for ALI treatment.

Process in menstrual blood-derived mesenchymal stem cells for treatment of central nervous system diseases

Stem cell research has become a frontier in the field of life sciences, and provides an ideal model for exploring developmental biology problems such as embryogenesis, histiocytosis, and gene expression regulation, as well as opens up new doors for clinical tissue defective and inheritance diseases. Among them, menstrual blood-derived stem cells (MenSCs) are characterized by wide source, multi-directional differentiation potential, low immune rejection characteristics. Thus, MenSCs can achieve individual treatment and have the most advantage of the clinical application. The central nervous system, including brain and spinal cord, is susceptible to injury. And lethality and morbidity of them tops the list of all types of trauma. Compared to peripheral nervous system, recovery of central nervous system after damage remains extremely hard. However, the treatment of stem cells, especially MenSCs, is expected to solve this problem. Therefore, biological characteristics of MenSCs and their treatment in the respect of central nervous system diseases have been reviewed at home and abroad in recent years, so as to provide reference for the treatment of central nervous system diseases.

Transplantation of Human Menstrual Blood-Derived Mesenchymal Stem Cells Alleviates Alzheimer's Disease-Like Pathology in APP/PS1 Transgenic Mice.

Extracellular β-amyloid (Aβ) plaques and neurofibrillary tangles (NFTs) are the pathological hallmarks of Alzheimer’s disease (AD). Mesenchymal stem cells (MSCs) have shown therapeutic efficacy in many neurodegenerative diseases, including AD. Human menstrual blood-derived stem cells (MenSCs) are a novel source of MSCs advantageous for their higher proliferation rate and because they are easy to obtain without ethical concerns. Although MenSCs have exhibited therapeutic efficacy in some diseases, their effects on AD remain elusive. In the present study, we showed that intracerebral transplantation of MenSCs dramatically improved the spatial learning and memory of APP/PS1 mice. In addition, MenSCs significantly ameliorated amyloid plaques and reduced tau hyperphosphorylation in APP/PS1 mice. Remarkably, we also found that intracerebral transplantation of MenSCs markedly increased several Aβ degrading enzymes and modulated a panel of proinflammatory cytokines associated with an altered microglial phenotype, suggesting an Aβ degrading and anti-inflammatory impact of MenSCs in the brains of APP/PS1 mice. In conclusion, these findings suggest that MenSCs are a promising therapeutic candidate for AD.

Menstrual blood-derived mesenchymal stem cells as a potential tool for cartilage regeneration

Purpose: Human mesenchymal stem cells (MSCs) are multipotent cells found in almost all human tissues. These cells are of great interest in regenerative medicine due to their high potential to differentiate into several directions including osteocytes, adipocytes and chondrocytes. Menstrual blood has been proposed as one of the perspective MSCs sources (MenSCs), due to their ease of access, as compared to the classical bone marrow MSCs (BMMSCs). As MSCs exhibit high chondrogenic differentiation potential, they ideally suit for therapeutic use in cartilage regeneration. Transforming growth factor β (TGF-β) has been considered as one of the major factors for induction of chondrogenic response in BMMSCs, however a member of the TGF-β superfamily Activin A also seems to contribute in the early stages of MSC chondrogenesis. Activin A seems necessary for the maintenance of self-renewal and pluripotency of MSCs. Furthermore there is an increasing body of evidence that Ca2+-dependent regulatory mechanisms can influence differentiation potential of chondrogenic progenitor cells, whereas Activin A was shown to increase free calcium concentrations in cells. Since Activin A also regulates menstrual cycle, we hypothesized that it may influence chondrogenic differentiation of MenSCs. The aim of this study was to characterize MenSCs and their chondrogenic differentiation capacity using two different growth factors - TGF-β3 and Activin A. The data was compared to the classical BMMSCs. Methods: BMMSCs and MenSCs were isolated from different healthy donors. Different cell surface markers (CD90, CD73, CD105, CD44, CD45, CD14, CD36, CD55, CD54, CD63, CD271, CD106, CD34, CD10, Stro1, Notch1) were analysed by flow cytometry. Cell proliferation capacity was determined by CCK-8 proliferation kit. Intracellular calcium was measured using fluorescent dye Cal-520. Adipogenic differentiation capacity was determined by Oil-Red staining and osteogenic differentiation by Alizarin Red staining. Chondrogenic differentiation (Activin A and TGF-b3 stimulation) was investigated by immuno- and histochemical staining with collagen II antibodies and safranin O, respectively. Results: In contrast to BMMSCs, MenSCs exhibited higher expression of CD10 and Notch1, and higher proliferative capacity. Furthermore, MenSCs exhibited higher level of intracellular calcium concentration as compared to BMMSCs. Adipogenic differentiation of MenSCs was weaker, whereas osteogenic differentiation capacity was higher compared to BMMSCs. Chondrogenic differentiation in BMMSCs was stronger with TGF-β3 than with Activin A, while MenSCs chondrogenic differentiation was remarkably more pronounced with Activin A than with TGF-β3. Conclusions: Taken together, our results demonstrate that MenSCs exhibit similar stem cell properties to BMMSCs, better proliferation potential and different regulatory mechanisms in chondrogenesis in vitro. Menstrual blood seems a convenient stem cells source for isolation of MSCs with chondrogenic differentiation potential, as does not require any invasive surgical interventions, and thus provides an option of repeated sample collection in the same donor, which make MenSCs a perspective tool in cartilage regenerative medicine.

The Research Progress of Clinical Applications of Human Menstrual Blood-Derived Mesenchymal Stem Cells

The Research Progress of Clinical Applications of Human Menstrual Blood-Derived Mesenchymal Stem Cells

Co-culture with endometrial stromal cells promotes the differentiation of menstrual blood-derived mesenchymal stem cells into endometrial epithelial cells

Objective: To study the potential of differentiation of menstrual blood-derived mesenchymal stem cells (MenSC) into endometrial epithelial cells (EEC) in vitro. Methods: Endometrial stromal cells (ESC) and MenSC were cultured and identified by certain methods.MenSC were co-cultured with ESC, added 10 ng/ml TGF-β1, 10 ng/ml EGF, 10 ng/ml PDGF-BB and 1×10(-7) mol/L 17-β-estradiol.The expression of cytokeratin, which was marker of EEC, was tested by immunofluorescence in differentiated MenSC. Results: MenSC proliferated quickly in vitro, and showed fusiform shape and clear structure within 10 generations.The expression rate of superficial markers of MenSC, CD44, CD90, CD73, and CD29, were 98.4%, 90.77%, 94.75% and 97.01% respectively.The expression of vimentin, which was stromal marker, was positive in cultured ESC (P3). After co-cultured with ESC for 3 weeks, MenSC morphology changed from fibroblast-like cells into epithelial-like cells.Immunofluorescence assay showed that the differentiated MenSC expressed cytokeratin. Conclusion: Under the condition of co-culture with ESC, MenSC has the ability to differentiate into endometrial epithelial cells. Cell growth factor and estrogen play the important roles in this process.

Human menstrual blood-derived mesenchymal stem cells as a cellular vehicle for malignant glioma gene therapy.

Despite many advances in conventional treatment strategies, there is no effective treatment modality for malignant gliomas. Gene therapy may offer a promising option for gliomas and several gene therapy approaches have shown anti-tumor efficiency in previous studies. Mesenchymal stem cell-based gene therapies, in which stem cells are genetically engineered to express therapeutic molecules, have shown tremendous potential because of their innate homing ability. In this study, human menstrual blood-derived MSCs (MenSC), a novel type of multipotential MSCs displays tropism for human malignant glioma when used as a gene delivery vehicle for therapeutics. Secretable trimeric TRAIL (stTRAIL) contains the receptor-binding domain of TRAIL, a death ligand that induces apoptosis in tumor cells. To overexpress stTRAIL, MenSCs were infected with efficient adenoviral serotype 35 vectors that had no influence on its broad multipotency and low immunophenotype. The modified MenSCs served as an excellent local drug delivery system for tumor site-specific targeted delivery and demonstrated therapeutic efficacy in an animal xenografts tumor model of U-87 MG cells. The MenSC-stTRAIL cells induced antitumor effects in vitro by significantly increasing apoptosis (P < 0.05). It also significantly reduced tumor burden in vivo (P < 0.05). The results showed that the proliferation of tumor cells was significantly reduced (P < 0.05). The MenSC, as a cellular delivery vehicle has a wide potential therapeutic role, which includes the treatment of tumors.

Transplantation of Menstrual Blood-Derived Mesenchymal Stem Cells Promotes the Repair of LPS-Induced Acute Lung Injury.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are associated with high morbidity and mortality. Menstrual blood-derived stem cells (MenSCs) have been shown to be good therapeutic tools in diseases such as ovarian failure and cardiac fibrosis. However, relevant studies of MenSCs in ALI have not yet proceeded. We hypothesized that MenSC could attenuate the inflammation in lipopolysaccharide (LPS)-induced ALI and promote the repair of damaged lung. ALI model was induced by LPS in C57 mice, and saline or MenSCs were administered via tail vein after four hours. The MenSCs were subsequently detected in the lungs by a live imaging system. The MenSCs not only improved pulmonary microvascular permeability and attenuated histopathological damage, but also mediated the downregulation of IL-1β and the upregulation of IL-10 in bronchoalveolar lavage fluid (BALF) and the damaged lung. Immunohistochemistry revealed the increased expression of proliferating cell nuclear antigen (PCNA) and the reduced expression of caspase-3 indicating the beneficial effect of MenSCs. Keratinocyte growth factor (KGF) was also upregulated after MenSCs administrated. As shown using transwell co-culture, the MenSCs also could improve the viability of BEAS-2B cells and inhibit LPS-induced apoptosis. These findings suggest that MenSC-based therapies could be promising strategies for treating ALI.

Human Menstrual Blood-Derived Mesenchymal Stem Cells as Potential Cell Carriers for Oncolytic Adenovirus.

Antitumor efficacy of systemically administered oncolytic adenoviruses (OAdv) is limited due to diverse factors such as liver sequestration, neutralizing interactions in blood, elimination by the immune system, and physical barriers in tumors. It is therefore of clinical relevance to improve OAdv bioavailability and tumor delivery. Among the variety of tumor-targeting strategies, the use of stem cells and specifically bone marrow-derived mesenchymal stem cells (BM-MSCs) is of particular interest due to their tumor tropism and immunomodulatory properties. Nonetheless, the invasive methods to obtain these cells, the low number of MSCs present in the bone marrow, and their restricted in vitro expansion represent major obstacles for their use in cancer treatments, pointing out the necessity to identify an alternative source of MSCs. Here, we have evaluated the use of menstrual blood-derived mesenchymal stem cells (MenSCs) as cell carriers for regional delivery of an OAdv in the tumor. Our results indicate that MenSCs can be isolated without invasive methods, they have an increased proliferation rate compared to BM-MSCs, and they can be efficiently infected with different serotype 5-based capsid-modified adenoviruses, leading to viral replication and release. In addition, our in vivo studies confirmed the tumor-homing properties of MenSCs after regional administration.