This study was designed to assess the safety and efficacy of human umbilical cord mesenchymal stem cells (UC-MSCs) in the treatment of rheumatoid arthritis (RA). In this ongoing cohort, 172 patients with active RA who had inadequate responses to traditional medication were enrolled. Patients were divided into two groups for different treatment: disease-modifying anti-rheumatic drugs (DMARDs) plus medium without UC-MSCs, or DMARDs plus UC-MSCs group (4×10⁷ cells per time) via intravenous injection. Adverse events and the clinical information were recorded. Tests for serological markers to assess safety and disease activity were conducted. Serum levels of inflammatory chemokines/cytokines were measured, and lymphocyte subsets in peripheral blood were analyzed. No serious adverse effects were observed during or after infusion. The serum levels of tumor necrosis factor-alpha and interleukin-6 decreased after the first UC-MSCs treatment (P<0.05). The percentage of CD4⁺CD25⁺Foxp3⁺ regulatory T cells of peripheral blood was increased (P<0.05). The treatment induced a significant remission of disease according to the American College of Rheumatology improvement criteria, the 28-joint disease activity score, and the Health Assessment Questionnaire. The therapeutic effects maintained for 3–6 months without continuous administration, correlating with the increased percentage of regulatory T cells of peripheral blood. Repeated infusion after this period can enhance the therapeutic efficacy. In comparison, there were no such benefits observed in control group of DMARDS plus medium without UC-MSCs. Thus, our data indicate that treatment with DMARDs plus UC-MSCs may provide safe, significant, and persistent clinical benefits for patients with active RA.

Background: The traditional anti-inflammation disease-modifying anti-rheumatic drugs (DMARDs) have limited therapeutic effects in rheumatoid arthritis (RA) patients. We previously reported the safety and efficacy of umbilical cord mesenchymal stem cell (UC-MSC) treatment in RA patients that were observed for up to 8 months after UC-MSC infusion. The aim of this study is to assess the long-term efficacy and safety of UC-MSC along with DMARDs for the treatment of RA. Methods: 64 RA patients aged 18–64 years were recruited in the study. During the treatment, patients were treated with 40 mL UC-MSC suspension product (2 × 10⁷ cells/20 mL) via intravenous injection immediately after the infusion of 100 mL saline. The serological markers tests were used to assess safety and the 28-joint disease activity score (DAS28) and the Health Assessment Questionnaire (HAQ) to assess efficacy. Results: 1 year and 3 years after UC-MSC cells treatment, the blood routine, liver and kidney function and immunoglobulin examination showed no abnormalities, which were all in the normal range. The ESR, CRP, RF of 1 year and 3 years after treatment and anti-CCP of 3 years after treatment were detected to be lower than that of pretreatment, which showed significant change (P < 0.05). Health index (HAQ) and joint function index (DAS28) decreased 1 year and 3 years after treatment than before treatment (P < 0.05). Conclusion: UC-MSC cells plus DMARDs therapy can be a safe, effective and feasible therapeutic option for RA patients.

Stem cell factor (SCF) plays important roles in tumor growth and angiogenesis. However, its regulatory mechanism remains largely undefined. Here, we report that hypoxia upregulated the expression of SCF in MCF-7 breast cancer cells in both messenger RNA and protein levels. When hypoxia-inducible factor (HIF)-1α expression was knocked down by RNA interference, the MCF-7 cell expression of SCF was decreased significantly. Furthermore, the SCF receptor, c-kit phosphorylation was significantly strengthened by the condition culture media from hypoxic MCF-7 and MCF-7-c cells. The survival of A549 cells was more dependent on SCF under hypoxia. Analysis of SCF promoter 5′-flanking region revealed a potential hypoxia-response element (HRE; 5′-GCGTG-3′) located at −68 to −64 relative to the transcriptional start site. Chromatin immunoprecipitation assay demonstrated that HIF-1α directly bound to this region under normoxia, and this binding activity was significantly enhanced under hypoxia. Overexpression of HIF-1α significantly upregulated the expression of luciferase reporter gene under control of the SCF promoters in both MCF-7 cells and human embryonic kidney 293 cells, but mutation of the HRE site completely blocked this effect. Epidermal growth factor was also able to enhance the SCF expression under normoxia in MCF-7 cells, which was dependent on HIF-1α. Taken together, our data demonstrated that HIF-1α was a key regulator of SCF expression in breast cancer cells. Hypoxia and epidermal growth factor receptor signal coexisted in the tumor microenvironment and might promote angiogenesis through HIF-1α-mediated upregulation of SCF and other angiogenic factors.

Cell-based therapy represents a promising strategy in the treatment of neurological disorders. Human umbilical cord tissue has recently been recognized as an ideal source of mesenchymal stromal cells due to accessibility, vast abundance and safety. Here, an intracerebral hemorrhage (ICH) rat model was established by injection of bacterial collagenase VII and CM-DiI labeled human umbilical cord tissue derived mesenchymal stromal cells (UC-MSC) were intracerebrally transplanted into rat brain 24 h after ICH. The results demonstrated that UC-MSC treatment significantly improved neurological function deficits and decreased injury volume of ICH rats. Leukocytes infiltration, microglial activation, ROS level and matrix metalloproteinases (MMPs) production were substantially reduced in peri-ICH area in cell-treated group as compared with PBS control at day 3 post-transplantation. In addition, UC-MSC treatment significantly increased vascular density in peri-ICH area and transplanted UC-MSC were found to be able to incorporate into cerebral vasculature in ipsilateral hemisphere at 14 days after transplantation. In summary, intracerebral administration of UC-MSC could accelerate neurological function recovery of ICH rat, the underlying mechanism may ascribe to their ability to inhibit inflammation and promote angiogenesis. Thus UC-MSC may provide a potential cell candidate for cell-based therapy in neurological disorders.

Background. Human umbilical cord multipotent mesenchymal stromal cells (UC-MSC) have recently been identified as ideal candidate stem cells for cell-based therapy. The present study was designed to evaluate therapeutic potentials of intracerebral administration of UC-MSC in a rat model of stroke. Methods. Rats were subjected to 2-hr middle cerebral artery occlusion and received 2×10⁵ UC-MSC or phosphate-buffered saline as a control. Neurologic function evaluation was conducted weekly after transplantation. Brain injury volume and in vivo differentiation of transplanted UC-MSC were detected 2 or 5 weeks after the UC-MSC treatment. In addition, vascular density, vascular endothelial growth factor, and basic fibroblast growth factor expression in ipsilateral hemisphere after treatment and in vitro angiogenic potential of UC-MSC were assessed. Results. The transplanted UC-MSC survived for at least 5 weeks in rat brain. Compared with the phosphate-buffered saline control, the UC-MSC treatment significantly reduced injury volume and neurologic functional deficits of rats after stroke. In ischemic brain, UC-MSC widely incorporated into cerebral vasculature and a subset of them was capable of differentiating into endothelial cells. Furthermore, the UC-MSC treatment substantially increased vascular density and vascular endothelial growth factor and basic fibroblast growth factor expression in ipsilateral hemisphere of stroke. In vitro induction and tube formation assay further confirmed their angiogenic properties. Conclusions. UC-MSC transplantation could accelerate neurologic functional recovery of rats after stroke, which may be mediated by their ability to promote angiogenesis.