Cord-derived Mesenchymal Stem Cell Transplantation Research Articles

Injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells promotes functional recovery in patients with spontaneous intracerebral hemorrhage: phase I clinical trial.

Animal experiments have shown that injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells can promote recovery from spinal cord injury. To investigate whether injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells can be used to treat spontaneous intracerebral hemorrhage, this non-randomized phase I clinical trial recruited patients who met the inclusion criteria and did not meet the exclusion criteria of spontaneous intracerebral hemorrhage treated in the Characteristic Medical Center of Chinese People's Armed Police Force from May 2016 to December 2020. Patients were divided into three groups according to the clinical situation and patient benefit: control (n = 18), human umbilical cord-derived mesenchymal stem cells (n = 4), and combination (n = 8). The control group did not receive any transplantation. The human umbilical cord-derived mesenchymal stem cells group received human umbilical cord-derived mesenchymal stem cell transplantation. The combination group received injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells. Patients who received injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells had more remarkable improvements in activities of daily living and cognitive function and smaller foci of intracerebral hemorrhage-related encephalomalacia. Severe adverse events associated with cell transplantation were not observed. Injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells appears to have great potential treating spontaneous intracerebral hemorrhage.

Efficacy of robot-assisted core decompression combined with human umbilical cord-derived mesenchymal stem cell transplantation for osteonecrosis of the femoral head.

The aim of this paper was to evaluate the effects of robot-assisted core decompression combined with human umbilical cord-derived mesenchymal stem cell (hUC-MSC) transplantation for early-stage osteonecrosis of the femoral head (ONFH). A retrospective analysis was performed on 18 patients with a total of 26 hips who were diagnosed with Association Research Circulation Osseous stage 2 avascular necrosis of the femoral head and who received core decompression combined with hUC-MSC transplantation. All surgeries were completed under robotic assistance. Preoperative and postoperative visual analogue scale (VAS) scores and the Harris Hip Score (HHS) were recorded to assess clinical function. A Magnetic Resonance Imaging (MRI) examination was performed at the last follow-up. The mean follow-up was 18.6 months (12-28 months), the VAS score (4.5±0.8 vs. 0.9±0.2, t=12.6, p≤0.001) and HHS (79.5±5.8 vs. 60.5±4.6, t=14.3, p≤0.001) were significantly improved at the last follow-up, compared with preoperative value. The MRI results showed that the necrotic volume of the femoral heads was significantly reduced. Robot-assisted core decompression combined with hUC-MSC transplantation is a feasible and relatively safe method for the treatment of femoral head necrosis.

Umbilical cord-derived mesenchymal stem cell transplantation for COVID -19 patients: long-term benefits for lung regeneration

Coronavirus disease 2019 (COVID-19) has affected hundreds of millions of people worldwide. Currently, mortality due to COVID-19 is significantly reduced by vaccination, antiviral drugs, and some improved treatments. Mesenchymal stem cell (MSC) transplantation—particularly umbilical cord-derived MSC (UC-MSC)—has been used as an adjuvant therapy for COVID-19 with some clinical evidence (reviewed in the publication). Moreover, a recent piece published in eBiomedicine (part of The Lancet, https://doi.org/10.1016/j.ebiom.2021.103789) in the previous month showed the long-term effects of UC-MSC transplantation in COVID-19 in a 1-year follow-up randomized, double-blind, placebo-controlled trial, demonstrating significantly recovered lung lesions and symptoms compared to the control group (i.e., without UC-MSC transplantation). In this commentary, we would like to discuss the value of UC-MSC transplantation for COVID-19 patients based on the results from this study and suggest applying this therapy for COVID-19 patients.

Therapeutic potential of human umbilical cord-derived mesenchymal stem cells transplantation in rats with optic nerve injury.

Purpose:There are no effective treatments currently available for optic nerve transection injuries. Stem cell therapy represents a feasible future treatment option. This study investigated the therapeutic potential of human umbilical cord–derived mesenchymal stem cell (hUC-MSC) transplantation in rats with optic nerve injury.Methods:Sprague–Dawley (SD) rats were divided into three groups: a no-treatment control group (n = 6), balanced salt solution (BSS) treatment group (n = 6), and hUC-MSCs treatment group (n = 6). Visual functions were assessed by flash visual evoked potential (fVEP) at baseline, Week 3, and Week 6 after optic nerve crush injury. Right eyes were enucleated after 6 weeks for histology.Results:The fVEP showed shortened latency delay and increased amplitude in the hUC-MSCs treated group compared with control and BSS groups. Higher cellular density was detected in the hUC-MSC treated group compared with the BSS and control groups. Co-localized expression of STEM 121 and anti-S100B antibody was observed in areas of higher nuclear density, both in the central and peripheral regions.Conclusion:Peribulbar transplantation of hUC-MSCs demonstrated cellular integration that can potentially preserve the optic nerve function with a significant shorter latency delay in fVEP and higher nuclear density on histology, and immunohistochemical studies observed cell migration particularly to the peripheral regions of the optic nerve.

Allogeneic umbilical cord-derived mesenchymal stem cell transplantation for treating chronic obstructive pulmonary disease: a pilot clinical study

IntroductionChronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. COPD results from chronic inflammation of the lungs. Current treatments, including physical and chemical therapies, provide limited results. Stem cells, particularly mesenchymal stem cells (MSCs), are used to treat COPD. Here, we evaluated the safety and efficacy of umbilical cord-derived (UC)-MSCs for treating COPD.MethodsTwenty patients were enrolled, 9 at stage C and 11 at stage D per the Global Initiative for Obstructive Lung Disease (GOLD) classification. Patients were infused with 106 cells/kg of expanded allogeneic UC-MSCs. All patients were followed for 6 months after the first infusion. The treatment end-point included a comprehensive safety evaluation, pulmonary function testing (PFT), and quality-of-life indicators including questionnaires, the 6-min walk test (6MWT), and systemic inflammation assessments. All patients completed the full infusion and 6-month follow-up.ResultsNo infusion-related toxicities, deaths, or severe adverse events occurred that were deemed related to UC-MSC administration. The UC-MSC-transplanted patients showed a significantly reduced Modified Medical Research Council score, COPD assessment test, and number of exacerbations. However, the forced expiratory volume in 1 s, C-reactive protein, and 6MWT values were nonsignificantly reduced after treatment (1, 3, and 6 months) compared with those before the treatment.ConclusionSystemic UC-MSC administration appears to be safe in patients with moderate-to-severe COPD, can significantly improve their quality of life, and provides a basis for subsequent cell therapy investigations.Trial registrationISRCTN, ISRCTN70443938. Registered 06 July 2019

Therapeutic evidence of umbilical cord-derived mesenchymal stem cell transplantation for cerebral palsy: a randomized, controlled trial

BackgroundCerebral palsy (CP) is a syndrome of childhood movement and posture disorders. Clinical evidence is still limited and sometimes inconclusive about the benefits of human umbilical cord mesenchymal stem cells (hUC-MSCs) for CP. We conducted a randomized trial to evaluate the safety and efficacy of hUC-MSC transplantation concomitant with rehabilitation in patients with CP.MethodsEligible patients were allocated into the hUC-MSC group and control group. In addition to rehabilitation, the patients in the hUC-MSC group received four transfusions of hUC-MSCs intravenously, while the control group received a placebo. Adverse events (AEs) were collected for safety evaluation in the 12-month follow-up phase. Primary endpoints were assessed as activities of daily living (ADL), comprehensive function assessment (CFA), and gross motor function measure (GMFM) scales. In addition, cerebral metabolic activity was detected by 18F-FDG-PET/CT to explore the possible mechanism of the therapeutic effects. Primary endpoint data were analyzed by ANOVA using SPSS version 20.0.ResultsForty patients were enrolled, and 1 patient withdrew informed consent. Therefore, 39 patients received treatments and completed the scheduled assessments. No significant difference was shown between the 2 groups in AE incidence. Additionally, significant improvements in ADL, CFA, and GMFM were observed in the hUC-MSC group compared with the control group. In addition, the standard uptake value of 18F-FDG was markedly increased in 3 out of 5 patients from the hUC-MSC group at 12 months after transplantation.ConclusionsOur clinical data showed that hUC-MSC transplantation was safe and effective at improving the gross motor and comprehensive function of children with CP when combined with rehabilitation. Recovery of cerebral metabolic activity might play an essential role in the improvements in brain function in patients with CP. The therapeutic window, transfusion route, and dosage in our study were considerable for reference in clinical application.Trial registrationChictr.org.cn, ChiCTR1800016554. Registered 08 June 2018—retrospectively registered. The public title was “Randomized trial of umbilical cord-derived mesenchymal stem cells for cerebral palsy.”

Intravenous Umbilical Cord-derived Mesenchymal Stem Cells Transplantation Regulates Hyaluronic Acid and Interleukin-10 Secretion Producing Low-grade Liver Fibrosis in Experimental Rat.

Introduction:Immunomodulation properties of mesenchymal stem cells have attracted tremendous attention that eventually could regress liver fibrosis process.Aim:The study aims to demonstrate the immunomodulation activities of Umbilical cord-derived Mesenchymal stem cells (UC-MSCs) affecting interleukin-10 (IL-10) and hyaluronic acid (HA) secretion post intraperitoneal injection of CCl4, potent hepatotoxin, induced liver fibrosis among experimental rats.Methods:There were 18 Sprague-Dawley (SD) rats divided into three treatment groups (G1 sham group, G2 untreated liver fibrosis group, and G3 UC-MSCs treated-group) and isolated in Stem Cell and Cancer Research Facility, Semarang, Indonesia. Blood examination was conducted after 3 and 14 days of UC-MSCs transplantation using sandwich based ELISA followed by the histopathological analysis of rat liver tissue. ANOVA and posthoc LSD tests were determined the significance against all groups based on their quantitative measurement.Results:UC-MSCs have been successfully extracted and isolated as well as positive with osteogenic differentiation (Alizarin dye). In further analysis, there were significant mean differences among all groups through the ANOVA test, both IL-10 and HA secretion, concurrent with low-grade liver fibrosis in G3. IL-10 elevates during the early phase of UC-MSCs transplantation, and HA significantly reduced on the 14th day of transplantation, it characterizes the liver fibrosis that has been attenuated.Conclusion:The transplantation of UC-MSCs has given an opportunity for the treatment of a wide range of chronic liver diseases through the immunomodulation properties via its paracrine effects that regulate specific cytokine to suppress fibrosis development.

The effects of human umbilical cord-derived mesenchymal stem cell transplantation on endometrial receptivity are associated with Th1/Th2 balance change and uNK cell expression of uterine in autoimmune premature ovarian failure mice

BackgroundTo explore the mechanism of human umbilical cord-derived mesenchymal stem cell (hUMSC) transplantation to improve ovarian function and the endometrial receptivity in autoimmune premature ovarian failure (POF) mice.MethodsThe POF model was established in mice treated with zona pellucida 3 polypeptide fragment (zona pellucida 3, ZP3). The hUMSCs were transplanted into the POF mice through tail vein injection. Following the transplantation, the serum hormone levels of follicle stimulating hormone (FSH), estrogen (E2), progesterone (P), γ-interferon (IFN-γ), interleukin-2 (IL-2), and interleukin-4 (IL-4) were evaluated by ELISA analysis. Morphological changes of ovarian and uterus tissues were examined by HE staining and immunohistochemistry. The expression of Th1/Th2 cytokines of T cells in spleen and CD56+CD16− cells (uterine natural killer cells, uNK cells) in uterine was measured by flow cytometry (FCM) and immunohistochemistry. The expression of HOXA10 in uterine endometrium was examined by immunohistochemistry and RT-PCR analysis. The pinopodes of epithelial cells in uterine endometrium were examined by scanning electron microscopy.ResultsFollowing hUMSC transplantation, the serum levels of E2, P, and IL-4 were increased but FSH, IFN-γ, and IL-2 levels were decreased in POF mice. Also, the transplantation of hUMSCs caused an increase in total number of healthy follicles and decrease of atresia follicles. The expression of HOXA10 gene was significantly increased but the CD56+CD16− uNK cells decreased in the endometrium of uterine. The ratio of Th1/Th2 cytokines was also significantly decreased.ConclusionThe data suggest that the recovery of ovarian function and endometrial receptivity in POF mice was regulated by the balance of Th1/Th2 cytokines and expression of uNK cells in the endometrium following hUMSC transplantation.

Combination Treatments of Plasma Exchange and Umbilical Cord-Derived Mesenchymal Stem Cell Transplantation for Patients with Hepatitis B Virus-Related Acute-on-Chronic Liver Failure: A Clinical Trial in China.

Background Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a common type of liver failure with a high mortality. This study aimed at investigating the safety and efficacy of the combination treatment of plasma exchange (PE) and umbilical cord-derived mesenchymal stem cell (UC-MSCs) transplantation for HBV-ACLF patients. Methods A total of 110 HBV-ACLF patients treated in our hospital from January 2012 to September 2017 were enrolled into this trial and divided into the control group (n = 30), UC-MSC group (n = 30), PE group (n = 30), and UC-MSC + PE group (n = 20) based on their treatments. The hepatic function, coagulation, and virological and immunological markers were assessed at baseline and 30, 60, 90, 180, and 360 days. The endpoint outcomes were death and unfavorable outcome (need for liver transplantation or death). Results The UC-MSC + PE group had the lowest rates of death and unfavorable outcome at 30 days, 60 days, and 90 days posttreatment among the four groups, but the difference did not reach significances. The multivariate logistic regression analysis demonstrated that hemoglobin, prothrombin activity, and MELD (model for end-stage liver disease) score were the independent factors associated with the unfavorable outcome (all P < 0.05). The levels of total bilirubin, alanine aminotransferase, aspartate transaminase, and MELD score were significantly decreased during treatments (all P < 0.05). Conclusion UC-MSCs combined with PE treatment had good safety but cannot significantly improve the short-term prognosis of HBV-ACLF patients with as compared with the single treatment. The long-term efficacy should be further evaluated. This trial is registered with registration no. NCT01724398.

Mesenchymal stem cells induced CD4+ T cell apoptosis in treatment of lupus mice

Umbilical cord-derived mesenchymal stem cell transplantation (UCMSCT) has been used to treat human autoimmune diseases like lupus for example, but little is known about its effect on cell apoptosis. Here we evaluated the efficacy of UCMSCT for lupus treatment and explored the mechanism by which mesenchymal stem cells (MSCs) modulate T cell apoptosis in lupus mice. 1 × 106 human umbilical cord-derived mesenchymal stem cells (UC-MSCs) were injected into B6.MRL-Faslpr (B6.lpr) mice via tail vein. 6 h, 24 h or 4 weeks later, the mice were sacrificed and the apoptosis of lymphocytes in peripheral blood and spleen were detected by flow cytometry. The immune cell subpopulations in spleen were also measured at 6 h and 24 h, respectively. The therapeutic effects were assessed after 4 weeks. The frequency of peripheral blood CD4+ T cell apoptosis was reduced in lupus-prone B6.lpr mice. UCMSCT alleviated the disease phenotypes in B6.lpr mice, decreased the ratio of Th1 as well as Th2 cells, and increased percentages of apoptotic CD4+ T cells in vivo and vitro. Collectively, our findings unravel that UCMSCT alleviate lupus disease and reverse immune imbalance possibly by promoting T cell apoptosis in B6.lpr mice.

The Effect of Umbilical Cord-derived Mesenchymal Stem Cell Transplantation in a Patient with Cerebral Palsy: A Case Report.

BackgroundCerebral Palsy (CP) is the most common motor disability reason of childhood that occurs secondarily to non-progressive damage in the brain whose development is still ongoing.Methods6-year-old dystonic-spastic male CP patient received allogenic mesenchymal stem cells treatment four times as 1×106/kg in intrathecal and intravenous administration of Umbilical Cord-derived mesenchymal stem cells (UC-MSCs) ways. Before and after the treatment, the patient was followed-up with FIM (Functional Independent Measurement), GMFCS (Gross Motor Function Classification System 88), Tardieu Scale, TCMS (Trunk Control Measurement Scale), MACS (Manual Ability Classification Scale), CFSS (Communication Function Classification System) for 18 months and received intensive rehabilitation.ResultsImprovements were observed especially in functional scales except for the Tardieu Scale, and no adverse effects were detected aside from a slight pain in the back.ConclusionWider future case studies on UC-MSCs will enable us to assess the efficacy of UC-MSCs which have positive impacts especially on functional scales.

Umbilical cord-derived mesenchymal stem cell transplantation for treating elderly vascular dementia.

This study aimed to determine the efficacy and safety of human umbilical cord-derived mesenchymal stem cell (HUC-MSC) transplantation for treating elderly vascular dementia (VaD). Ten VaD patients (average age, 73.88years old) were treated. HUC-MSCs were isolated, cultured, stem cell-marked, and qualified and administered as a 3-course intravenous infusion to these patients. The Mini-Mental State Exam (MMSE) and the Activities of Daily Living Index (Barthel Index scoring system) were used to assess the cognitive function and daily living activity improvements in these patients before transplantation (T0), 3months after transplantation (T1), and 6months after transplantation (T2). The MMSE and Barthel Index scores were 15.80±5.49 and 42.00±9.33 points at T0, respectively, and were significantly different when compared with those at T1 (19.20±6.39 and 49.20±10.86 points, respectively, P<0.05), whereas there was no difference when compared with those at T2 (14.00±6.55 and 40.70±10.37 points, respectively, P>0.05). HUC-MSC transplantation was safe and feasible for VaD and improved early cognitive functions and daily living activities in VaD patients to a certain extent, thus improving patients' quality of life.

Umbilical Cord-Derived Mesenchymal Stem Cell Transplantation in Hepatitis B Virus Related Acute-on-Chronic Liver Failure Treated with Plasma Exchange and Entecavir: a 24-Month Prospective Study.

Search for an effective therapy for patients with hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) remains an important issue. This study investigated the efficacy of umbilical cord-derived mesenchymal stem cell (UC-MSC) transplantation in patients with HBV-ACLF. 45 consecutive entecavir-treated HBV-ACLF patients were prospectively studied. Among these patients, 11 received both plasma exchange (PE) and a single transplantation of UC-MSCs (group A), while 34 received only PE (group B). The primary endpoint was survival at 24months. Compared with group B, levels of albumin, alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, prothrombin time (PT), international normalized ratio (INR) and model for end-stage liver disease score in group A improved significantly at 4weeks after transplantation (p<0.05). Levels of albumin, PT and INR in group A were also markedly improved at 24months (p<0.05). Group A had significantly higher cumulative survival rate at 24months (54.5% v.s. 26.5%, p=0.015 by log rank test). Between the two groups, levels of creatinine, White blood cell, hemoglobin and platelet were similar. HBeAg loss and hepatocellular carcinoma incidence were similar at 24months. Group assignment (relative risk: 2.926, 95%confidence interval: 1.043-8.203, p=0.041) was an independent predictor for survival at 24months. Success rate of UC-MSC transplantation was 100% in group A. No severe adverse event was observed in any patient. UC-MSC transplantation is safe and effective for HBV-ACLF patients treated with PE and entecavir. It further improves the hepatic function and survival.

Study of differentiated human umbilical cord-derived mesenchymal stem cells transplantation on rat model of advanced parkinsonism.

The aim of this study was to explore the curative effect of differentiated human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) transplantation on rat of advanced Parkinson disease (PD) model. Human umbilical cord-derived mesenchymal stem cells were cultured and induced differentiation in vitro. The PD rats were established and allocated randomly into 2 groups: differentiated hUC-MSCs groups and physiological saline groups (the control group). Rotation test and immunofluorescence double staining were done. The result showed that hUC-MSCs could differentiate into mature dopamine neurons. Frequency of rotation was significantly less in differentiated hUC-MSCs groups than in normal saline group. After we transplanted these cells into the unilateral lesioned substantia nigra induced by striatal injection of 6-hydroxydopamine and performed in the medial forebrain bundle and ventral tegmental area, nigral tyrosine hydroxylase-positive cells were observed and survival of at least 2months. In addition, transplantation of hUC-MSCs could make an obviously therapeutic effect on PD rats.

Umbilical cord-derived mesenchymal stem cell transplantation combined with hyperbaric oxygen treatment for repair of traumatic brain injury.

Transplantation of umbilical cord-derived mesenchymal stem cells (UC-MSCs) for repair of traumatic brain injury has been used in the clinic. Hyperbaric oxygen (HBO) treatment has long been widely used as an adjunctive therapy for treating traumatic brain injury. UC-MSC transplantation combined with HBO treatment is expected to yield better therapeutic effects on traumatic brain injury. In this study, we established rat models of severe traumatic brain injury by pressurized fluid (2.5-3.0 atm impact force). The injured rats were then administered UC-MSC transplantation via the tail vein in combination with HBO treatment. Compared with monotherapy, aquaporin 4 expression decreased in the injured rat brain, but growth-associated protein-43 expression, calaxon-like structures, and CM-Dil-positive cell number increased. Following combination therapy, however, rat cognitive and neurological function significantly improved. UC-MSC transplantation combined with HBO therapyfor repair of traumatic brain injury shows better therapeutic effects than monotherapy and significantly promotes recovery of neurological functions.

Prospective controlled trial of safety of human umbilical cord derived-mesenchymal stem cell transplantation in patients with decompensated liver cirrhosis

To evaluate the safety of human umbilical cord derived-mesenchymal stem cell (UC-MSC) transplantation therapy in patients with decompensated liver cirrhosis. UC-MSCs were transplanted intravenously into patients with decompensated liver cirrhosis. Serum levels of glucose (GLU), total cholesterol (TC), blood urea nitrogen (BUN), alpha fetoprotein (AFP), white blood cells (WBC), and prothrombin activity (PA) were detected at different time points after UC-MSCs transplantation. Most UC-MSC transplanted patients experienced an improvement in quality of life, to varying degrees. With the exception of low-grade fever in a few patients, side effects and oncogenic events were rare (treatment group: 1/38 vs. control group: 1/16; P more than 0.05). The UC-MSCs transplantation showed no effect on GLU, TC, BUN, AFP, WBC, or PA. UC-MSCs transplantation in patients with decompensated liver cirrhosis is safe and may improve the patient's quality of life.

Allogeneic transplantation of umbilical cord-derived mesenchymal stem cells for diffuse alveolar hemorrhage in systemic lupus erythematosus

Umbilical cord-derived mesenchymal stem cell transplantation (UC-MSCT) has been proved to be effective in the treatment of systemic lupus erythematosus (SLE), based on animal experiments and clinical trials. Diffuse alveolar hemorrhage (DAH) is a rare complication of SLE with a high mortality usually over 50%. This study aimed to assess the efficacy of UC-MSCT in the treatment of SLE-associated DAH. Four SLE patients complicated with DAH, who underwent UC-MSCT, were included. Clinical changes before and after transplantation were assessed by measurements of hemoglobin, platelet level, oxygen saturation, and serological factors. High-resolution CT (HRCT) scans of the chest were performed to evaluate pulmonary manifestation. All the four patients showed dramatic improvements of their clinical manifestations. Hemoglobin was elevated after UC-MSCT and was sustained at a normal level 6 months after UC-MSCT in the four patients. Platelet level was upregulated in two patients who had thrombocytopenia at baseline. Oxygen saturation appeared to be normal at 1 month after UC-MSCT, and this result was confirmed by the HRCT scan of the chest. Serum albumin elevated to 3.5 g/dl 6 months after transplantation. Our findings suggest that UC-MSCT results in amelioration of oxygen saturation as well as hematological and serologic changes, which revealed that UC-MSCT could be applied as a salvage strategy for DAH patients.

Treatment of refractory systemic sclerosis with human umbilical cord-derived mesenchymal stem cell transplantation

Treatment of refractory systemic sclerosis with human umbilical cord-derived mesenchymal stem cell transplantation

Treatment of refractory systemic sclerosis with human umbilical cord-derived mesenchymal stem cell transplantation

Treatment of refractory systemic sclerosis with human umbilical cord-derived mesenchymal stem cell transplantation