Umbilical Cord Mesenchymal Stem Cells Group Research Articles

Umbilical Cord Mesenchymal Stem Cells Combined with Fufang Xueshuantong Capsule Attenuate Oxidative Stress and Vascular Lesions in Diabetic Rats by Activating Nrf-2/HO-1 Signaling Pathway

Background:: Macrovascular lesions are the main cause of death and disability in diabetes mellitus, and excessive accumulation of cholesterol and lipids can lead to long-term and repeated damage of vascular endothelial cells. Umbilical cord mesenchymal stem cells (UCMSCs) can attenuate vascular endothelial damage in type 1 diabetic mice, while Fufang Xueshuantong capsule (FXC) has a protective effect on endothelial function; however, whether FXC in combination with UCMSCs can improve T2DM macrovascular lesions as well as its mechanism of action are not clear. Therefore, the aim of this study was to reveal the role of FXC + UCMSCs in T2DM vasculopathy and their potential mechanism in the treatment of T2DM. Methods:: The control and T2DM groups were intragastrically administered with equal amounts of saline, the UCMSCs group was injected with UCMSCs (1×106, resuspended cells with 0.5 mL PBS) in the tail vein, the FXC group was intragastrically administered with 0.58 g/kg FXC, and the UCMSCs + FXC group was injected with UCMSCs (1×106) in the tail vein, followed by FXC (0.58 g/kg), for 8 weeks. Results:: We found that FXC+UCMSCs effectively reduced lipid levels (TG, TC, and LDL-C) and ameliorated aortic lesions in T2DM rats. Meanwhile, Nrf2 and HO-1 expression were upregulated. We demonstrated that inhibition of Nrf-2 expression blocked the inhibitory effect of FXC+UCMSCs-CM on apoptosis and oxidative stress injury. Conclusion:: Our data suggest that FXC+UCMSCs may attenuate oxidative stress injury and macroangiopathy in T2DM by activating the Nrf-2/HO-1 pathway.

Human Umbilical Cord Mesenchymal Stem Cells Improve Lung Function in Chronic Obstructive Pulmonary Disease Rat Model Through Regulating Lung Microbiota.

The use of human umbilical cord mesenchymal stem cells (UC-MSCs) has shown promise in improving the pathophysiological characteristics of rats with chronic obstructive pulmonary disease (COPD). However, more research is needed to understand the exact mechanism behind their therapeutic effects and their impact on lung microbiota. To investigate this, rats were randomly assigned to one of 3 groups: Control, COPD + vehicle, and COPD + UC-MSCs group. Lung function changes after UC-MSCs therapy were evaluated weekly for 6 weeks. Additionally, lactate dehydrogenase (LDH), TNF (tumor necrosis factor)-α, IL (interleukin)-6, and IL-1β level in bronchoalveolar lavage fluid (BALF) were analyzed. Arterial blood gas and weight were recorded. Hematoxylin and eosin (HE) staining was used to examine lung pathology, while changes in the lung microbiota were evaluated through 16S rRNA sequencing. The administration of UC-MSCs in rats led to a progressive amelioration of COPD, as demonstrated by enhanced lung function and reduced inflammatory response. UC-MSCs treatment significantly altered the structure and diversity of the lung microbiota, effectively preventing microbiota dysbiosis. This was achieved by increasing the abundance of Bacteroidetes and reducing the levels of Proteobacteria. Additionally, treatment with UC-MSCs reduced the activation of pathways associated with COPD, including microbial metabolism, ABC transporters, and Quorum sensing. The group of UC-MSCs showed increased metabolic pathways, such as amino acid biosynthesis, purine metabolism, starch and sucrose metabolism, and biosynthesis of secondary metabolites, compared to the COPD group. The use of UC-MSCs was found to reduce inflammation and improve lung function in rats with COPD. The mechanism may be related to the lung microbiota, as UC-MSCs improved the communities of lung microbiota and regulated dysregulated metabolic pathways.

Comparative study on the efficacy of PRP gel and UC-MSCs gel as adjuvant therapies in the treatment of DFU wounds.

Diabetic foot ulcer (DFU) is a common and serious complication of diabetes, and its treatment is challenging. Platelet-rich plasma (PRP) gel and umbilical cord mesenchymal stem cells (UC-MSCs) gel have been concerned as new therapies for DFU in recent years, and comparative studies on the efficacy and mechanisms of these methods, however, are rarely reported. Thirty patients with DFU were selected and divided into the PRP group and the UC-MSCs group, and wound healing, foot blood vessels (ABI index), infection index (CRP), neuropathy symptoms (TCSS score), and foot skin temperature before and after treatment were compared between the two groups. SPSS 21.0 was used for statistical analysis. The results showed that the efficacy of the UC-MSCs gel group was significantly better than that of the PRP group in terms of wound healing rate, time to complete wound closure, ABI index, CRP level and TCSS score. No statistically significant difference in foot skin temperature was observed between the two groups. The efficacy of UC-MSCs gel is significantly superior to that of PRP gel in the treatment of DFU, with shortened time to complete wound closure, increased wound healing rate, better pain and infection control, and improved vascular and neurological symptoms.

Cell-Based Regenerative Endodontics for the Treatment of Irreversible Pulpitis: AnIn VivoInvestigation

IntroductionThis study aims to investigate the ability of umbilical cord mesenchymal stem cells (UC-MSC) to enhance the regeneration of pulp-dentin complex in immature permanent teeth with irreversible pulpitis. MethodsA total of 32 mandibular premolar teeth with immature apices in 5 dogs were used in this in-vivo randomized controlled trial (RCT). Eight healthy teeth without pre-existing pathosis served as the positive control samples and received no treatment, while in another 8 teeth, the pulp was completely extirpated (negative control). Class V cavities were prepared to induce inflammation in the remaining 16 teeth (groups 3 and 4) and the pulp was extirpated 2-4 mm short of the radiographic apex. Of the 16, the 8 teeth in group 4 received 1 mL of cord blood stem cells with a hydrogel scaffold. Blood clots were covered with mineral trioxide aggregates at the cementoenamel junction in the experimental groups, and teeth were filled with RMGI and composite. Three months later, block sections were removed for histologic evaluations for the evaluation of postoperative apical closure, degree of inflammation, and presence of normal pulp tissue. The data were statistically analyzed with the chi-square test (P < .05). ResultsAll teeth with complete pulp extirpation demonstrated pulpal necrosis with no postoperative closure of their apices, while apical closure was seen in all the teeth in the remaining groups. There was a statistically significant (P < .001) difference in the presence of inflammation and normal pulp tissue between the experimental groups. The teeth in group 3 showed normal pulp tissue extending to the level of MTA, but there was inflammation within the canal space. In contrast, the teeth in the UC-MSC group demonstrated organized, normal pulp tissue with no inflammation. ConclusionBased on these results, the regeneration of the pulp-dentin complex is possible with no inflammation when UC-MSCs are used and 2-4 mm of the apical pulp remains intact in immature teeth with irreversible pulpitis.

Clinical evaluation of intralesional umbilical cord-derived mesenchymal stem cells, conditioned medium and triamcinolone acetonide injection for keloid treatment: A pilot study.

Topical keloid therapy is performed with triamcinolone acetonide (TA) intralesional injection. However, the recurrence rate is high with various side effects. Mesenchymal stem cells (MSCs) have high proliferative abilities and reduce the activity and proliferation of fibroblast cells in keloids. To overcome the costs and limitations, conditioned medium (CM) is used. This study aims to evaluate feasibility of intralesional injection of umbilical cord MSC (UC-MSC) and conditioned medium (UC-CM) compared to TA for keloid therapy. Twenty-four patients with keloids who met the inclusion criteria were included, randomized into three treatment groups and then got assessed for the sociodemographic data, keloid volume, histopathology (type 1:3 collagen ratio), interleukin-10 (IL-10) levels and Patient and Observer Scar Assessment Scale (POSAS) score during visits. Largest volume regression occurred in the UC-MSC group, followed by UC-CM and then the TA group (UC-MSC: 45.32% ± 2.61%; UC-CM: 43.61% ± 3.67%; TA: 28.34% ± 3.81%; p = 0.003). Similar pattern was also observed in increase in IL-10 levels, the decrease in POSAS scores and the reduction of type 1:3 collagen ratio. Hence, UC-MSC and UC-CM are promisingly more effective than TA for keloid therapy, showcasing their superiority in reducing keloid volume, symptoms and type 1:3 collagen ratio, as well as increasing the levels of IL-10.

Assessing keloid treatment efficacy: a comparison of intralesional umbilical-cord mesenchymal stem cells, their conditioned medium, and triamcinolone acetonide injection through macroscopic and microscopic examination

Link Video Abstract: https://youtu.be/NAnsqP7dPd0 Background: Current keloid treatment involves intralesional injection of triamcinolone acetonide (TA), which, despite its usage, is associated with high recurrence rates and adverse effects. Mesenchymal stem cells (MSCs) exhibit potent proliferative abilities and can curb fibroblast activity and proliferation within keloids. It is now known that umbilical cord mesenchymal stem cells (UC-MSCs) have been shown to have greater proliferative potential than bone marrow-derived MSCs (BM-MSCs), and other advantages of UC-MSCs include being easily accessible and less immunogenic. To assess the viability of administering umbilical cord MSC (UC-MSC) and its conditioned medium (UC-CM) via intralesional injection compared to TA in reducing macroscopic keloid volume and type 1:3 collagen ratio. Methods: This randomized controlled trial enrolled twenty-four keloid patients by consecutive sampling. Eligible patients were required to have keloids on the chest, back, abdomen, or extremities. Patients with hypertrophic scars, a history of kidney failure, hypertension, blood disorders, malignancy, pregnancy, breastfeeding, or keloid treatment were excluded. Sociodemographic data, keloid size, and tissue biopsies were collected during scheduled visits. Bivariate analyses applied were considered significant at a p-value of &lt;0.05. Results: The study revealed that the most significant decrease in macroscopic volume occurred within the UC-MSC group, followed by the UC-CM group, and then the TA group (UC-MSC: 50.24% ± 3.58%; UC-CM: 43.97% ± 3.04%; TA: 33.53% ± 2.64; p = 0.004. The UC-CM group exhibited the most substantial decrease in the type 1:3 collagen ratios (4.80±0.26), with UC-MSC (4.60(4.15-8.05)) and TA (3.96(1.63-4.14)) following in sequence (p=0.002). Conclusion: The findings of this study indicate that the use of UC-MSC and UC-CM exhibits promising superiority over TA in terms of reducing macroscopic keloid volume and type 1:3 collagen ratio.

HOXA10 Expressing UCMSCs Transplantation Improved Endometrial Receptivity on Endometrial Injury.

Endometrial injury is considered the major cause of female infertility. Traditional therapies such as estrogen substitution therapy are not satisfactory due to individual variation in response to treatment, thereby warranting the use of alternative strategies such as stem cell therapy. Transplantation of stem cells, such as umbilical cord mesenchymal stem cells (UCMSCs), has been shown to improve endometrial healing. However, due to the effect of the intrauterine environment, the therapeutic effect of UCMSCs is limited, and its efficacy is unstable. HOXA10, encoded by the HOXA10 gene, plays an important role in endometrium morphology maintenance, proliferation, differentiation, and embryo implantation. Moreover, UCMSCs do not show HOXA10 expression. Our study aimed to evaluate the therapeutic effects of HOXA10-transfected UCMSCs on endometrial injury repair in vivo. First, we established T10-UCMSCs (UCMSCs transfected with HOXA10) for transplantation. To establish the endometrial injury model, we injected 95% ethanol into the uterine cavity and transplanted T10-UCMSCs into the uterine cavity from the cornua uteri. Fourteen days later, uteri were collected for histological and biochemical analysis of endometrial growth and receptivity. Our results showed the endometrial receptivity was better in T10-UCMSCs group than in UCMSCs group, suggesting that HOXA10 could enhance the repairing ability of UCMSCs in the endometrium injury repair. More importantly, the fertility test showed that more embryos were implanted in the T10- UCMSCs group. Our results suggest that UCMSCs with HOXA10 expression could improve the therapeutic effects on endometrial injury repairing.

UC-MSCs promote frozen-thawed ovaries angiogenesis via activation of the Wnt/β-catenin pathway in vitro ovarian culture system

BackgroundOvarian tissue cryopreservation and transplantation are novel therapeutic approaches for fertility preservation. However, follicle loss caused by ischemic and hypoxic damage is one of the issues after frozen-thawed ovarian tissue transplantation. Promoting angiogenesis in grafts is the key to restore cryopreserved ovarian function. Mesenchymal stem cells (MSCs) have been reported to facilitate angiogenesis in the cryopreserved ovarian tissue transplantation. However, the risk of embolization, immunogenic effect and tumorigenesis hinders the clinical application of MSCs to human organ transplantation. In this study, we established an in vitro ovarian culture system to restore frozen-thawed ovarian function before transplantation with the application of umbilical cord mesenchymal stem cells (UC-MSCs), and explored the effects of UC-MSCs on frozen-thawed ovaries in vitro ovarian culture system and the mechanisms of UC-MSCs on the angiogenesis of frozen-thawed ovaries.MethodsA simple in vitro three dimensional (3D) ovarian culture system using Matrigel was established to support to an ideal niche, and ovary was alone cultured in the 24-well plate as a control. We also evaluated the effects of UC-MSCs treatment on ovarian function with or without Matrigel support. All thawed ovaries were randomly divided into control group (Matrigel−/UC-MSCs−), Matrigel group (Matrigel+/UC-MSCs−), UC-MSCs group (Matrigel−/UC-MSCs+) and UC-MSCs + Matrigel group (Matrigel+/UC-MSCs+). HE staining was used to detect the histological structure of follicles and TUNEL staining was used to detect cell apoptosis. The number of microvessels was counted to evaluate neovascularization. The mRNA expression of VEGFA, IGF1 and ANGPT2 were detected by RT-PCR. Western blotting was used to measure the expression of GSK-3β, β-catenin and p-β-catenin.ResultsIn the absence of UC-MSCs, 3D culture system supported by Matrigel showed significantly improved follicular development and microvascular number. Additionally, UC-MSCs were also found to effectively improve follicular development and microvascular number regardless of the culture condition used. However, alleviated follicular apoptosis, increased mRNA expression of angiogenesis-related gene and activated Wnt/β-catenin pathway occurred only in the UC-MSCs + Matrigel group. Besides, with the application of IWP-2 in UC-MSCs + Matrigel group, Wnt//β-catenin pathway could be blocked by IWP-2 serving as one of Wnt/β-catenin pathway inhibitors.ConclusionsThis in vitro study showed the beneficial effects of UC-MSCs on thawed ovaries and explored a potential mechanism inducing angiogenesis. In particular, 3D ovarian culture system supported by Matrigel further improved UC-MSCs treatment. The in vitro culture system using Matrigel and UC-MSCs may provide a potential treatment strategy for improving the success rate of thawed ovaries transplantation.

Umbilical Cord Mesenchymal Stem Cells Ameliorate Kidney Injury in MRL/Ipr Mice Through the TGF-β1 Pathway.

The therapeutic effects and mechanism of umbilical cord mesenchymal stem cells (UC-MSC) on kidney injury in MRL/Ipr mice were studied. UC-MSC, methylprednisolone (MP), and their combination were used to treat MRL/Ipr mice. The therapeutic effects were evaluated by renal function assessment, and HE, PAS, and Masson staining were carried out on renal tissues and visualized by electron microscopy. Subsequently, podocyte injury was detected by the presence of podocin in renal tissues by immunofluorescence. To further explore the mechanism, serum TGF-β1 was measured, and TGF-β1, p-Smad3, and TRAF6 in the renal tissue were detected by Western blotting. In vitro, TGF-β1 was used to stimulate podocytes, and the podocyte activity and changes in synaptopodin were observed after UC-MSC treatment. Significant improvements in renal function and pathological injury were observed in the UC-MSC group compared to the lupus nephritis (LN) model group. UC-MSC and MP treatment improved podocyte injury in MRL/Ipr mice. Western blot examination showed a significant increase in TGF-β1, p-Smad3, and TRAF6 expression in renal tissues of the LN model group, while significant downregulation of those proteins was observed in the UC-MSC group. After TGF-β1 stimulation in vitro, podocyte activity decreased, and UC-MSC treatment improved podocyte activity and restored synaptopodin expression. UC-MSC therapy could improve the deterioration of renal function and the pathological changes of the renal tissues in MRL/Ipr mice. Our study suggested that UC-MSC may improve kidney injury and podocyte injury in LN mice by inhibiting the TGF-β1 pathway.

Intra-Articular Injection of Umbilical Cord Mesenchymal Stem Cells Loaded With Graphene Oxide Granular Lubrication Ameliorates Inflammatory Responses and Osteoporosis of the Subchondral Bone in Rabbits of Modified Papain-Induced Osteoarthritis.

AimThis study is to investigate the effects of umbilical cord mesenchymal stem cells (UCMSCs) loaded with the graphene oxide (GO) granular lubrication on ameliorating inflammatory responses and osteoporosis of the subchondral bone in knee osteoarthritis (KOA) animal models.MethodsThe KOA animal models were established using modified papain joint injection. 24 male New Zealand rabbits were classified into the blank control group, GO group, UCMSCs group, and GO + UCMSCs group, respectively. The concentration in serum and articular fluid nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), type II collagen (COL-II), and glycosaminoglycan (GAG) was detected using ELISA, followed by the dissection of femoral condyles and staining of HE and Micro-CT for observation via the microscope.ResultsGO granular lubrication and UCMSCs repaired the KOA animal models. NO, IL-6, TNF-α, GAG, and COL-II showed optimal improvement performance in the GO + UCMSCs group, with statistical significance in contrast to the blank group (P <0.01). Whereas, there was a great difference in levels of inflammatory factors in serum and joint fluid. Micro-CT scan results revealed the greatest efficacy of the GO + UCMSCs group in improving joint surface damage and subchondral bone osteoporosis. HE staining pathology for femoral condyles revealed that the cartilage repair effect in GO + UCMSCs, UCMSCs, GO, and blank groups were graded down.ConclusionUCMSCs loaded with graphene oxide granular lubrication can promote the secretion of chondrocytes, reduce the level of joint inflammation, ameliorate osteoporosis of the subchondral bone, and facilitate cartilage repair.

Comparative Study of a Modified Sub-Tenon's Capsule Injection of Triamcinolone Acetonide and the Intravenous Infusion of Umbilical Cord Mesenchymal Stem Cells in Retinitis Pigmentosa Combined With Macular Edema.

Retinitis pigmentosa (RP) is a hereditary retinal degenerative disease leading to eventual blindness. When RP is combined with macular edema (ME), the visual impairment further worsens. We compared a modified sub-Tenon’s capsule injection of triamcinolone acetonide (TA) and the intravenous infusion of umbilical cord mesenchymal stem cells (UCMSCs) in the treatment of RP combined with ME (RP-ME) to assess their safety and efficacy in eliminating ME and restoring visual function. A phase I/II clinical trial enrolled 20 patients was conducted. All patients were followed up for 6 months. There were no severe adverse effects in both groups. In retinal morphological tests, the central macular thickness (CMT) in TA group significantly decreased at first week, first and second month after injection (p < 0.05). The CMT in UCMSCs group significantly decreased at first month after infusion. The rate of reduction of CMT in TA group was significantly greater than that in UCMSCs group at second month (p < 0.05). Reversely, the rate of reduction of CMT in UCMSCs group was significantly greater than that in TA group at sixth month (p < 0.05). In visual functional test, although there were no significant differences in visual acuity or visual fields within each group or between groups, but the amplitude of P2 wave of flash visual evoked potential (FVEP) showed significant increasing in TA group at second month in UCMSCs group at sixth month (p < 0.05). At 6th month, the rate of growth in the amplitude of P2 wave in USMCSs group was significantly greater than that in TA group (p < 0.05). This study suggests both modified sub-Tenon’s capsule injection of TA and intravenous infusion of UCMSCs are safe for RP-ME patients. TA injection is more effective at alleviating ME while improving visual function in a short term. UCMSC intravenous infusion shows slow but persistent action in alleviating ME, and can improve the visual function for a longer time. These approaches can be applied separately or jointly depending on the disease condition for patients to benefit maximumly. Clinical Trial Registration: http://www.chictr.org.cn, identifier ChiCTR-ONC-16008839

Recovery of motor function in rats with complete spinal cord injury following implantation of collagen/silk fibroin scaffold combined with human umbilical cord-mesenchymal stem cells

This study aimed to assess the effect of the collagen/silk fibroin scaffolds seeded with human umbilical cord-mesenchymal stem cells on functional recovery after acute complete spinal cord injury.The fibroin and collagen were mixed (mass ratio, 3:7), and the composite scaffolds were produced. Forty rats were randomly divided into the Sham group (without spinal cord injury), spinal cord injury group (spinal cord transection without any implantation), collagen/silk fibroin scaffolds group (spinal cord transection with implantation of the collagen/silk fibroin scaffolds), and collagen/silk fibroin scaffolds + human umbilical cord-mesenchymal stem cells group (spinal cord transection with the implantation of the collagen/silk fibroin scaffolds co-cultured with human umbilical cord-mesenchymal stem cells). Motor evoked potential, Basso-Beattie-Bresnahan scale, modified Bielschowsky's silver staining, and immunofluorescence staining were performed.The BBB scores in the collagen/silk fibroin scaffolds + human umbilical cord-mesenchymal stem cells group were significantly higher than those in the spinal cord injury and collagen/silk fibroin scaffolds groups (p<0.05 or p<0.01). The amplitude and latency were markedly improved in the collagen/silk fibroin scaffolds + human umbilical cord-mesenchymal stem cells group compared with the spinal cord injury and collagen/silk fibroin scaffolds groups (p<0.05 or p<0.01). Meanwhile, compared to the spinal cord injury and collagen/silk fibroin scaffolds groups, more neurofilament positive nerve fiber ensheathed by myelin basic protein positive structure at the injury site were observed in the collagen/silk fibroin scaffolds + human umbilical cord-mesenchymal stem cells group (p<0.01, p<0.05). The results of Bielschowsky's silver staining indicated more nerve fibers was observed at the lesion site in the collagen/silk fibroin scaffolds + human umbilical cord-mesenchymal stem cells group compared with the spinal cord injury and collagen/silk fibroin scaffolds groups (p<0.01, p< 0.05).The results demonstrated that the transplantation of human umbilical cord-mesenchymal stem cells on a collagen/silk fibroin scaffolds could promote nerve regeneration, and recovery of neurological function after acute spinal cord injury.

Interference research of umbilical cord mesenchymal stem cells on the pulmonary fibrosis in silicosis rats

Objective: To explore the effect of the umbilical cord mesenchymal stem cells(UC-MSCs) on the pulmonary fibrosis in silicosis rats. Methods: SPF male Sprague Dawley rats were randomly divided into control group, silica model group and UC-MSCs treatment group with 12 rats each group. SiO(2) intra-tracheal injection(0.5 ml of 50 mg/ml/rat) were applied to silica model group and UC-MSCs treatment groups. After that UC-MSCs treatment group received 1 ml UC-MSCs suspension (3×10(6) cells/ml) by tail vein injection on the 29th, 36th, 43th and 50th day after exposure to the first silica suspension. On the 60th and 75th day after exposure to silica suspension, all animals were examed for pulmonary CT. Then the rats were euthanized on 75th day after the first exposure to silica.Lung's histopathological examination of the rats from all the groups were carried out. The content of hydroxyproline in lungs, TGF-β1 and IL-6 in serum were examined. Results: The lung's histopathological examination showed no obvious inflammatory cell and no fibrosis in the lung tissue of the control group, there were a lot of inflammatory cell aggregation and collagen fiber deposition in silica model group, while in the UC-MSCs intervention group and treatment group, there were less inflammatory cells and collagen fiber. The rats from silica model groups had higher HYP, TGF-β1 and IL-6 than the rats from UC-MSCs treatment group and control group. Lung fields of rats in the control group were clear and no obvious high-density shadow. Different-sized granular high-density shadows or reticular fibrous shadows were found diffusely distributed in the lungs of the rats in silica model group. Lung field of rats in UC-MSCs intervention group and treatment group were less high density shadows, and more clear. Conclusion: UC-MSCs can alleviate the pulmonary fibrosis in silica model rats through regulating the secretion of some fibrosis related cytokines.

Effects of umbilical cord mesenchymal stem cells on apoptosis of MCF-7 cells

Objective To study the effects of umbilical cord mesenchymal stem cells (UCMSCs) on the apoptosis of human breast cancer cell line MCF-7. Methods MCF-7 cells were co-cultured with different concentrations of UCMSCs. The apoptosis of MCF-7 cells was detected by in situ apoptosis and flow cytometry. Nude mouse subcutaneous tumor model was established by inoculating MCF-7 and MSCs cells subcutaneously on the right side of the back of a mouse. The MCF-7 cells were inoculated on the left side of the mouse as control. The tumor volume was measured every week to compare the difference between the two groups. On the 17th day after inoculation, the tumor tissue was harvested and the apoptosis of tumor cells was observed by a transmission electron microscopy. Results In situ apoptosis and flow cytometry showed that the early and late apoptosis rates of MCF-7 cells increased first and then decreased with the increase of UCMSCs concentration. The differences between the control and the MCF-7+UCMSCs group were statistically significant for early (F=39.80, P<0.001) and late apoptosis rates (F=5.68, P<0.01). The tumor volume of MCF-7+UCMSCs group was significantly lower than that of control group in 17 days after inoculation (F=9.81, P<0.01). The representative apoptotic cells were observed by the transmission electron microscopyin the MCF-7+UCMSCs group. Conclusion The UCMSCs with a certain concentration can effectively promote the apoptosis of MCF-7 cells. This study provides a certain experimental basis for the clinical treatment of breast cancer. Key words: Umbilical cord mesenchymal stem cells; Breast cancer cells; Cell apoptosis; Flow cytometry

Umbilical Cord Mesenchymal Stem Cell Treatment for Crohn's Disease: A Randomized Controlled Clinical Trial.

Background/AimsStem cell therapy has been applied to treat a variety of autoimmune diseases, including Crohn’s disease (CD), but few studies have examined the use of umbilical cord mesenchymal stem cells (UC-MSCs). This trial sought to investigate the efficacy and safety of UC-MSCs for the treatment of CD.MethodsEighty-two patients who had been diagnosed with CD and had received steroid maintenance therapy for more than 6 months were included in this study. Forty-one patients were randomly selected to receive a total of four peripheral intravenous infusions of 1×106 UC-MSCs/kg, with one infusion per week. Patients were followed up for 12 months. The Crohn’s disease activity index (CDAI), Harvey-Bradshaw index (HBI), and corticosteroid dosage were assessed.ResultsTwelve months after treatment, the CDAI, HBI, and corticosteroid dosage had decreased by 62.5±23.2, 3.4±1.2, and 4.2±0.84 mg/day, respectively, in the UC-MSC group and by 23.6±12.4, 1.2±0.58, and 1.2±0.35 mg/day, respectively, in the control group (p<0.01, p<0.05, and p<0.05 for UC-MSC vs control, respectively). Four patients developed a fever after cell infusion. No serious adverse events were observed.ConclusionsUC-MSCs were effective in the treatment of CD and produced mild side effects.

Effects of human umbilical cord mesenchymal stem cells on vascular endothelial growth factor and IL-6 expression in tissue of AMI rats

To investigate the effects of human umbilical cord mesenchymal stem cells (UC-MSCs) on vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) expression in acute myocardium infarction (AMI) rats. The human UC-MSCs were cultured to the 4th generation for experiment. Sixty male Sprague-Dawley (SD) rats were randomly divided into sham group, AMI model group and UC-MSCs group, with 20 in each group. AMI animal model was produced by ligation of anterior descending coronary artery; in the sham group, the threading vein was gone below without ligation. In UC-MSCs group 2×106 UC-MSCs were infused through the caudal vein at 24 hours after successful model production. The animals were sacrificed after 7 days; the myocardial tissue and coronary artery below the ligation line were harvested. The mRNA and protein expressions of IL-6 in myocardium were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western Blot. The positive expression of VEGF in coronary artery was observed by immunohistochemisty. Compared with the sham group, the mRNA and protein expressions of IL-6 in myocardium in AMI model group were increased significantly (gray value: 0.732±0.131 vs. 0.321±0.080, 0.678±0.191 vs. 0.286±0.061, both P < 0.05). Compared with the AMI model group, the mRNA and protein expressions of IL-6 in myocardium in UC-MSCs group were decreased significantly (gray value: 0.300±0.104 vs. 0.732±0.131, 0.312±0.101 vs. 0.678±0.191, both P < 0.05). Observation under light microscope, the VEGF positive cells in AMI model group was increased significantly compared with the sham group (cells/HP: 21.1±2.2 vs. 7.6±1.3, P < 0.05), the VEGF positive cells in UC-MSCs group were increased significantly compared with the AMI model group (cells/HP: 41.5±3.1 vs. 21.1±2.2, P < 0.05). Human UC-MSCs could promote angiogenesis by the improvement of VEGF in coronary artery and inhibit the inflammation by the reduction of IL-6 in rats with AMI.

Clinical observation of umbilical cord mesenchymal stem cell transplantation in treatment for sequelae of thoracolumbar spinal cord injury.

BackgroundUmbilical cord mesenchymal stem cells (UCMSCs) have a considerable advantage and potential in treating for central nervous system diseases and have become a novel alternative treatment for spinal cord injury. This study aims to compare the neurological function outcome of stem cell transplantation, rehabilitation therapy, and self-healing for sequelae of spinal cord injury.MethodsThirty-four cases of thoracolumbar spinal cord injury were randomly divided into three groups: the stem cell transplantation group was given CT-guided UCMSC transplantation twice; the rehabilitation group received rehabilitation therapy; and the blank control group did not receive any specific treatment. AIS grading, ASIA scoring, the manual muscle strength and muscle tension scale, and the Barthel index were used to evaluate the clinical outcome. Urodynamic examination was also performed for patients in the UCMSC group and the rehabilitation therapy group.ResultsSeven of the ten patients in the UCMSC group had significant and stable improvement in movement, self-care ability, and muscular tension; five of the forteen patients (36%) in the rehabilitation group also had certain improvement in these aspects. Urodynamic examination demonstrated that patients in the UCMSC group exhibited an increase in maximum urinary flow rate and maximum bladder capacity, as well as a decrease in residue urine volume and maximum detrusor pressure. The rehabilitation group exhibited decreased maximum bladder capacity, but no perceptible change in maximum urinary flow rate, residue urine volume or maximum detrusor pressure.ConclusionsUCMSC transplantation can effectively improve neurological functional recovery after spinal cord injury, and its efficacy is superior to that of rehabilitation therapy and self-healing.Trial registrationThe present clinical study was registered at chictr.org (registration number: NCT01393977).

Gene expression profile changes induced upon umbilical cord mesenchymal cell infusion therapy in a rat model of hepatic cirrhosis

To investigate changes in gene expression that occur upon treatment with human umbilical cord mesenchymal stem cells (UC-MSCs) for hepatic cirrhosis using a rat model system. Hepatic cirrhosis was induced in Sprague-Dawley rats by subcutaneous injection of carbon tetrachloride and oral administration of alcohol.UC-MSCs were isolated from human umbilical cord and the cells' immunophenotype and differentiation towards osteogenic and adipogenic lineages were confirmed.The UC-MSC sample or vehicle alone (phosphate buffered saline, PBS) was transplanted by intravenous injection.Histopathological staining and serological testing were used to compare the liver morphology and function among the different groups.The gene expression in the PBS group and UC-MSC group were detected by gene microarray and differences between the groups were statistically analyzed by t-test. Transplantation of the UC-MSCs improved liver function in the hepatic cirrhosis rats.Comparison of the gene expression profiles of the PBS group and the UC-MSC group showed that the latter had up-regulation of the genes related to the complement and coagulation cascades and down-regulation of the genes related to cell proliferation, cell cycle, and collagen synthesis. UC-MSC therapy might improve liver function in cirrhosis by increasing the expression of genes related to the complement and coagulation cascades and by decreasing genes involved in cell proliferation and collagen deposition.

Immunomodulatory effect of UC-MSC on function of immunocytes of rats with collagen type II induced arthritis

This study was purposed to observe the influence of umbilical cord mesenchymal stem cells (UC-MSC) on the peripheral blood CD4(+)CD25(+)regulatory T cells (Treg), Th17 cells and neutrophils in rats with collagen type II-induced arthritis(CIA), and to explore the regulating effect of UC-MSC transplantation on immunocyte subgroup. The rats wee divided into 3 groups: CIA group (model group), UC-MSC treated group and blank control group. The CIA rats were injected with UC-MSC via tail vein. The percentage of CD4(+)CD25(+) cells in peripheral blood and the expression of NCD11b on neutrophil surface in CIA rates was detected by flow cytometry (FCM), and the serum interleukin-17 (IL-17) was observed by enzyme-linked immunosorbent assay (ELISA). The results showed that the mean fluorescence intensity(MFI) of NCD11b and the level of IL-17 in the model group were significantly higher than those in the blank control group, and the ratio of CD4(+)CD25(+) cells were significantly lower (P < 0.05). The MIF of NCD11b and the level of IL-17 in the UC-MSC treated group were significantly lower than that in the model group (P < 0.05), while the proportion of CD4(+)CD25(+) Treg increased (P < 0.05). Since the fifth week, the above indicators in the UC-MSC group have almostly approached the control group. It is concluded that the UC-MSC can increase peripheral blood Treg proportion in CIA rat, inhibit the secretion of Th17 and the activity of neutrophils, reduce the immune inflammation reaction, decrease the release of proinflammatory factor, and induce immune reconstruction.

Reduction of Fibrosis in Dibutyltin Dichloride–Induced Chronic Pancreatitis Using Rat Umbilical Mesenchymal Stem Cells From Wharton’s Jelly

The objective of this study was to investigate the effects of rat umbilical cord mesenchymal stem cells (UCMSCs) from Wharton's jelly on dibutyltin dichloride (DBTC)-induced chronic pancreatitis (CP) and subsequent pancreatic fibrosis in rats. A rat model of CP induced by DBTC was used. Male Sprague-Dawley rats were randomly divided into 4 groups: the control, DBTC, DBTC + UCMSCs, and control + UCMSC groups. Umbilical cord mesenchymal stem cells were administered intravenously on day 5 after the administration of DBTC. On days 14 and 28, the rats were evaluated morphologically and biochemically. The expression levels of inflammatory cytokines and chemokines in the pancreatic tissues of different groups were evaluated using quantitative real-time polymerase chain reaction. The activation of pancreatic stellate cells was estimated by immunochemistry and Western blot analysis of α-smooth muscle actin. Umbilical cord mesenchymal stem cells were detected in inflamed pancreatic tissues. Umbilical cord mesenchymal stem cell treatment improved the histological scores and alleviated the fibrosis of pancreas samples, The expression of cytokines in the DBTC + UCMSC group was significantly lower than that in the DBTC group. Also, pancreatic stellate cell activation was inhibited by UCMSC treatment. Xenogeneic transplantation of UCMSCs is a novel approach for the treatment of CP and subsequent fibrosis. Umbilical cord mesenchymal stem cells may be a promising therapeutic intervention for human CP in the future.