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Based on the characteristics of modern weapon injury, a repetitive model of traumatic systemic inflammatory response syndrome (SIRS) and an evaluation system were established. The models were treated with GFP-labeled tree shrew umbilical cord mesenchymal stem cells (UCMSCs). Forty out of 50 tree shrews were used to make a unilateral femoral comminuted fracture. Lipopolysaccharide was injected intravenously to create a traumatic SIRS model. The other 10 shrews were used as normal controls. After the model was established for 10 days, 20 tree shrews were injected intravenously with GFP-labeled UCMSCs, and 18 tree shrews were not injected as the model control group. The distribution of GFP-labeled cells in vivo was measured at 2 and 10 days after injection. Twenty days after treatment, the model group, the normal control group, and the treatment group were taken to observe the pathological changes in each tissue, and blood samples were taken for the changes in liver, renal, and heart function. Distribution of GFP-positive cells was observed in all tissues at 2 and 10 days after injection. After treatment, the HE staining results of the treatment group were close to those of the normal group, and the model group had a certain degree of lesions. The results of liver, renal, and heart function tests in the treatment group were returned to normal, and the results in the model group were abnormally increased. UCMSCs have a certain effect on the treatment of traumatic SIRS and provide a new technical solution for modern weapon trauma treatment.

Background The tumorigenesis of infused umbilical cord mesenchymal stem cells (UC-MSCs) is being preclinically evaluated. Methods We observed tumor formation in NOD SCID mice after a single subcutaneous injection of hUC-MSCs and the effect of these cells on tumor growth in tumor-bearing mice. Three generations (P5, P7, and P10) of hUC-MSCs (1 × 107) from two donors (hUC-MSC1 and hUC-MSC2) were inoculated subcutaneously into NOD SCID mice. Subcutaneous transplantation models were established in NOD SCID mice with human cervical cancer HeLa cells (solid tumor) and human B cell lymphoma Raji cells (hematological tumor). Then, the animals were euthanized, gross dissection was performed, and tissues were collected. Various organs were observed microscopically to identify pathological changes and tumor metastasis. Results In the tumorigenesis experiment, no general anatomical abnormalities were observed. In the tumor promotion experiment, some animals in the HeLa groups experienced tumor rupture, and one animal died in each of the low- and medium-dose hUC-MSC groups. The results may have occurred due to the longer feeding time, and the tumor may have caused spontaneous infection and death. Pathological examination revealed no metastasis to distant organs in any group. In the Raji tumor model, some animals in each group experienced tumor rupture, and one animal in the medium-dose hUC-MSC group died, perhaps due to increased tumor malignancy. Thus, hUC-MSCs neither promoted nor inhibited tumor growth. No cancer cell metastasis was observed in the heart, liver, spleen, lungs, kidneys or other important organs, except that pulmonary venule metastasis was observed in 1 animal in the model group. Conclusions Injected hUC-MSCs were not tumorigenic and did not significantly promote or inhibit solid or hematological tumor growth or metastasis in NOD SCID mice.

Background To study the effect of allogeneic umbilical cord mesenchymal stem cell transplantation on the structure and function of the thymus in aged C57 mice and provide a new method for the treatment of senile thymic atrophy. Results The changes in the thymus cortex and medulla volume and the lymphocyte ratio were analyzed by immunofluorescence. For thymus tissue sections, immunohistochemical staining was performed to detect p16, p53, SOD, becline1, LC3b, p62, sirt1, and sirt3. Changes in CK5, CK8, CD4 and CD8 expression were observed. Treatment with mUCMSCs could promote hair regeneration in aging mice and regenerate the thymus structure. Conclusions mUCMSCs inhibited senescence of the thymus and promoted structural and functional thymus regeneration by downregulating the senescence genes p53 and p16 and upregulating the SOD, Sirt1 and Sirt3 genes, but the mechanism requires further research. Methods C57 mice were obtained and met the requirements of thymic aging. mUCMSCs were infused via the tail vein at a dose of 1×107 cells/kg twice per week for 3 weeks. Six weeks after the last transplantation, the thymus was weighed, and the thymus-to-body weight ratio was calculated. The thymus tissue was stained with HE.

Background: Umbilical cord mesenchymal stem cell transplantation can treat metabolic syndrome, but the tracing of cells in the body after transplantation has always been a problem. Tree shrew umbilical cord mesenchymal stem cells were labeled with the dark red fluorescent dye DIR and a metabolic syndrome model in tree shrew was generated. The migration, distribution, colonization and survival of the cells were observed. Methods: Tree shrew umbilical cord mesenchymal stem cells were labeled with the dark red fluorescent dye DIR. Three days after the tree shrew model was generated, the pancreas, kidney and liver were placed in a small animal live imager to observe the distribution of the labeled cells. Result: The labeled cells showed deep red fluorescence in the live imager. After treatment with the transplanted cells, dark red fluorescent signals were observed in the liver, kidney and pancreas of the tree shrews but not in the untreated group and no dark red fluorescent signal was observed in the cell distribution.

Inflammatory bowel disease (IBD) is a persistent and chronic disease that is characterized by destructive gastrointestinal (GI) inflammation. Researchers are trying to identify and develop new and more effective treatments with no side effects. Acute and chronic mouse models of IBD were established using dextran sulfate sodium (DSS) solution. To evaluate the efficacy and mechanism, umbilical cord mesenchymal stem cells (UCMSCs) were obtained from Kunming (KM) mice and humans. In the chronic IBD study, the survival rates of the normal control, model, mouse UCMSC (mUCMSC) and human UCMSC (hUCMSC) groups were 100%, 40%, 86.7%, and 100%, respectively. The histopathological scores of the normal control, intraperitoneal injection, intravenous treatment, and model groups were 0.5 ± 0.30, 5.9 ± 1.10, 8.7 ± 1.39, and 8.8 ± 1.33 (p = 0.021). UCMSCs promoted the expression of the intestinal tight junction protein occludin, downregulated the protein expression of the autophagy marker LC3A/B in colon tissue, and upregulated the expression of VEGF-A and VEGFR-1 at the injured site. This study provides an experimental model for elucidating the therapeutic effects of UCMSCs in IBD. We provide a theoretical basis and method for the clinical treatment of IBD using UCMSCs.

A model of allergic rhinitis (AR) in BALB/c mice was established and evaluated to provide experimental subjects for further research. Preparation of human umbilical cord mesenchymal stem cells (hUCMSCs), including isolation, expansion culture, passaging, cryopreservation, and preparation of cell suspensions, provided materials for experimental research and clinical treatment. The mouse AR model was established by ovalbumin (OVA) intraperitoneal injection and the nasal stimulation induction method, and the model had a good effect and high repeatability. GFP-labeled hUCMSCs had good effects and were stable cells that could be used for tracking in animals. Transplantation of hUCMSCs by intraperitoneal and tail vein injections had a specific effect on the AR model of mice, and tail vein injection had a better effect. Tracking of hUCMSCs in vivo showed that the three groups of mice had the greatest number of hUCMSCs in the nose at week 2. The mouse AR model was used to evaluate the efficacy of hUCMSC transplantation via multiple methods for AR. The distribution of hUCMSCs in vivo was tracked by detecting green fluorescent protein (GFP), and the treatment mechanism of hUCMSCs was elucidated. This study provides technical methods and a theoretical basis for the clinical application of hUCMSCs.

Umbilical cord mesenchymal stem cells (UC-MSCs) exert strong immunomodulatory effects and can repair organs. However, their roles in radiation injury remain unclear. We show that in tree shrews with acute radiation injury, injected UC-MSCs significantly improved survival rates, reduced lung inflammation and apoptosis, prevented pulmonary fibrotic processes, recovered hematopoiesis, and increased blood counts. A protein microarray analysis showed that serum levels of the anti-inflammatory cytokines IL-10 and IL-13 and the growth factors BMP-5, BMP-7, HGF, insulin, NT-4, VEGFR3, and SCF were significantly higher, while those of the inflammatory cytokines IL-2, TIMP-2, TNF-α, IFN-γ, IL-1ra, and IL-8 and the fibrosis-related factors PDGF-BB, PDGF-AA, TGF-β1, IGFBP-2, and IGFBP-4 were significantly lower in UC-MSC-injected animals. A transcriptome analysis of PBMCs showed that the mRNA expression of C1q was upregulated, while that of HLA-DP was downregulated after UC-MSC injection. These results confirm the immunohistochemistry results. eGFP-labeled UC-MSCs were traced in vivo and found in the heart, liver, spleen, lungs, kidneys, thymus, small intestine and bone marrow. Our findings suggest that UC-MSC transplantation may be a novel therapeutic approach for treating acute radiation injury.

Background/Aims: Stem cell-based therapy is attractive in many clinical studies, but current data on the safety of stem cell applications remains inadequate. This study observed the safety, immunological effect of cynomolgus monkey umbilical cord mesenchymal stem cells (mUC-MSCs) injected into cynomolgus monkeys, in order to evaluate the safety of human umbilical cord mesenchymal stem cells (hUC-MSCs) prepared for human clinical application. Methods: Eighteen cynomolgus monkeys were divided into three groups. Group 1 is control group, Group 2 is low-dose group, Group 3 is high-dose group. After repeated administrations of mUC-MSCs, cynomolgus monkeys were observed for possible toxic reactions. Results: During the experiment, no animal died. There were no toxicological abnormalities in body weight, body temperature, electrocardiogram, coagulation and pathology. In the groups 2 and 3, AST and CK transiently increased, and serum inorganic P slightly decreased. All animals were able to recover at 28 days after the infusion was stopped. In the groups 2 and 3, CD3+ and IL-6 levels significantly increased, and recovery was after 28 days of infusion. There were no obvious pathological changes associated with the infusion of cells in the general and microscopic examinations. Conclusions: The safe dosage of repeated intravenous infusion of mUC-MSCs in cynomolgus monkeys is 1.0 × 107/kg, which is 10 times of that in clinical human use.

Hindlimb ischemia is still a clinical problem with high morbidity and mortality. Patients suffer from consequent rest pain, ulcers, cool limbs, and even amputation. Angiogenesis is a promising target for the treatment of ischemic limbs, providing extra blood for the ischemic region. In the present study, we investigated the role of umbilical cord-derived mesenchymal stem cells (UC-MSCs) in regulating angiogenesis and relieving hindlimb ischemia. UC-MSCs were isolated from the umbilical cord of tree shrews. Angiography results showed that UC-MSCs injection significantly promoted angiogenesis in tree shrews. Moreover, the ankle brachial index, transcutaneous oxygen pressure, blood perfusion, and capillary/muscle fiber ratio were all markedly increased by the application of UC-MSCs. In addition, the conditioned culture of human umbilical vein endothelial cells using medium collected from UC-MSCs showed higher expression of angiogenic markers and improved migration ability. In short, the isolated UC-MSCs notably contributed to restoring blood supply and alleviating the symptoms of limb ischemia through enhancing angiogenesis.

Background The establishment of a tree shrew model for systemic lupus erythematosus (SLE) provides a new method to evaluate the pathogenesis of autoimmune diseases. Methods Eighty tree shrews were randomly divided into four groups receiving either an intraperitoneal injection of pristane, lipopolysaccharide (LPS), or pristane and LPS, or no injection. Three weeks after injection, the SLE model tree shrews were divided into the model group and the treatment group. Tree shrews in the treatment group and the normal control group were infused with umbilical cord mesenchymal stem cells (UC-MSCs). The cells were labeled with DiR. Two weeks after transplantation, three groups of tree shrews were analyzed for urine protein, serum antinuclear antibodies and antiphospholipid, and inflammatory cytokine antibody microarray detection. The heart, liver, spleen, lung, and kidney were collected from the three groups and subjected to hematoxylin and eosin (HE) staining and detection of renal immune complex deposition. Results HE staining indicated pathology in the model group. Red fluorescence revealed immune complex deposition in the kidneys from the model group. Conclusions The combined intraperitoneal injection of pristane and LPS is the best way to induce SLE pathological changes. The pathological changes improved after UC-MSC treatment.

The aim of this study was to establish a tree shrew metabolic syndrome model and demonstrate the utility of MSCs in treating metabolic syndrome. We used tree shrew umbilical cord mesenchymal stem cell (TS-UC-MSC) transplantation for the treatment of metabolic syndrome to demonstrate the clinical application of these stem cells and to provide a theoretical basis and reference methods for this treatment. Tree shrew metabolic syndrome model showed significant insulin resistance, high blood sugar, lipid metabolism disorders, and hypertension, consistent with the diagnostic criteria. TS-UC-MSC transplantation at 16 weeks significantly reduced blood sugar and lipid levels, improved insulin resistance and the regulation of insulin secretion, and reduced the expression levels of the pro-inflammatory cytokines IL-1 and IL-6 (P

Background. Systemic lupus erythematosus (SLE) is a multisystem disease that is characterized by the appearance of serum autoantibodies. No effective treatment for SLE currently exists.Methods. We used human umbilical cord mesenchymal stem cell (H-UC-MSC) transplantation to treat B6.Fas mice.Results. After four rounds of cell transplantation, we observed a statistically significant decrease in the levels of mouse anti-nuclear, anti-histone, and anti-double-stranded DNA antibodies in transplanted mice compared with controls. The percentage of CD4+CD25+Foxp3+T cells in mouse peripheral blood significantly increased after H-UC-MSC transplantation.Conclusions. The results showed that H-UC-MSCs could repair lesions in B6.Fas mice such that all of the relevant disease indicators in B6.Fas mice were restored to the levels observed in normal C57BL/6 mice.