STEM-08. GENE THERAPY USING IL-24-EXPRESSING UMBILICAL CORD-DERIVED MESENCHYMAL STEM CELLS AGAINST GLIOMA

Abstract Despite many advances have been made in treatment of gliomas, patients prognosis remains poor. Stem cell-based therapy has been thought to be a promising option for gliomas and many studies have reported that umbilical cord-derived mesenchymal stem cells (UC-MSCs) are ideal gene vectors for tumor gene therapy. Interleukin 24 (IL-24) is a pleiotropic immunoregulatory cytokine which has an apoptotic effect on many kinds of tumor cells and can inhibit the growth of tumors specifically without damaging normal cells. However, there are still some challenges in its clinical application, such as the half-life, toxicity caused by high-dose application, and so on. Therefore, we hypothesize that combination of gene transfer with stem cell transplantation could overcome the problems. In this study, we investigated UC-MSCs transduced with lentiviral vectors carrying IL-24 complementary DNA as a vehicle for the targeted delivery of IL-24 to local tumor sites. The engineered UC-MSCs selectively migrated to glioma cells and showed the antitumor effect in vitro and in vivo. The restrictive efficacy of these UC-MSCs was related to the inhibition of proliferation and induction of apoptosis in tumor cells. These findings indicate that UC-MSCs-based IL-24 gene therapy can obviously suppress the growth of glioma xenografts, thereby suggesting the potential for future therapeutic interventions in the treatment of gliomas. Keywords: Glioma, Gene therapy, Umbilical cord-derived mesenchymal stem cells (UC-MSCs), Interleukin 24 (IL-24)

Download Full-text

Chronic Toxicity Test in Cynomolgus Monkeys For 98 Days with Repeated Intravenous Infusion of Cynomolgus Umbilical Cord Mesenchymal Stem Cells

Cellular Physiology and Biochemistry ◽

10.1159/000481639 ◽

2017 ◽

Vol 43 (3) ◽

pp. 891-904 ◽

Cited By ~ 2

Author(s):

Jie He ◽

Guang-ping Ruan ◽

Xiang Yao ◽

Ju-fen Liu ◽

Xiang-qing Zhu ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Umbilical Cord ◽

Intravenous Infusion ◽

Dose Group ◽

High Dose ◽

Human Umbilical Cord ◽

Cynomolgus Monkeys ◽

Cell Based Therapy

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.

Download Full-text

Heterogeneity of Umbilical Cords as a Source for Mesenchymal Stem Cells

Dataset Papers in Biology ◽

10.7167/2013/370103 ◽

2013 ◽

Vol 2013 ◽

pp. 1-4 ◽

Cited By ~ 9

Author(s):

O. O. Maslova ◽

N. S. Shuvalova ◽

O. M. Sukhorada ◽

S. M. Zhukova ◽

O. G. Deryabina ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Mesenchymal Stem Cell ◽

Umbilical Cord ◽

Optimal Conditions ◽

Umbilical Cord Tissue ◽

Umbilical Cords

The object of the paper is to show the heterogeneity of 300 cord samples processed in the current research. The differences in effectiveness of mesenchymal stem cell (MSC) isolation are shown. Moreover, the recommendations for choosing the method of MSC isolation depending on the value of stromal-vascular rate are given. The data can be useful for selecting the optimal conditions to obtain MSC and for further cryopreservation of umbilical cord tissue.

Download Full-text

Human umbilical cord mesenchymal stem cells: an overview of their potential in cell-based therapy

Expert Opinion on Biological Therapy ◽

10.1517/14712598.2015.1051528 ◽

2015 ◽

Vol 15 (9) ◽

pp. 1293-1306 ◽

Cited By ~ 51

Author(s):

Tan Li ◽

Mingxu Xia ◽

Yuanyuan Gao ◽

Yanting Chen ◽

Yun Xu

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Umbilical Cord ◽

Human Umbilical Cord ◽

Cell Based Therapy

Download Full-text

Label-Free Rapid Separation and Enrichment of Bone Marrow-Derived Mesenchymal Stem Cells from a Heterogeneous Cell Mixture Using a Dielectrophoresis Device

Sensors ◽

10.3390/s18093007 ◽

2018 ◽

Vol 18 (9) ◽

pp. 3007 ◽

Cited By ~ 5

Author(s):

Junya Yoshioka ◽

Yu Ohsugi ◽

Toru Yoshitomi ◽

Tomoyuki Yasukawa ◽

Naoki Sasaki ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Gradient Method ◽

Label Free ◽

Rapid Separation ◽

Isolation System ◽

Tissue Samples ◽

Cell Based Therapy

Bone marrow-derived mesenchymal stem cells (BMSCs) are an important cell resource for stem cell-based therapy, which are generally isolated and enriched by the density-gradient method based on cell size and density after collection of tissue samples. Since this method has limitations with regards to purity and repeatability, development of alternative label-free methods for BMSC separation is desired. In the present study, rapid label-free separation and enrichment of BMSCs from a heterogeneous cell mixture with bone marrow-derived promyelocytes was successfully achieved using a dielectrophoresis (DEP) device comprising saw-shaped electrodes. Upon application of an electric field, HL-60 cells as models of promyelocytes aggregated and floated between the saw-shaped electrodes, while UE7T-13 cells as models of BMSCs were effectively captured on the tips of the saw-shaped electrodes. After washing out the HL-60 cells from the device selectively, the purity of the UE7T-13 cells was increased from 33% to 83.5% within 5 min. Although further experiments and optimization are required, these results show the potential of the DEP device as a label-free rapid cell isolation system yielding high purity for rare and precious cells such as BMSCs.

Download Full-text

Effects of Co-Culture of Graphene Oxide Scaffolds with Different Concentrations and Umbilical Mesenchymal Stem Cells on the Proliferation and Differentiation of Stem Cells

10.21203/rs.3.rs-164379/v1 ◽

2021 ◽

Author(s):

Aifeng Liu ◽

Jixin Chen ◽

Shuwei Gong ◽

Qiang Wei ◽

Ye Yuan

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Graphene Oxide ◽

Stem Cell ◽

Mesenchymal Stem Cell ◽

Umbilical Cord ◽

High Porosity ◽

Proliferation And Differentiation ◽

Scaffold Materials ◽

The Impact

Abstract The main role of the scaffold materials is to enable cells to survive in the scaffold binding as while as to further promote their proliferation and differentiation ability. For mesenchymal stem cell, the scaffold could provide an environment for them to maintain their phenotype, and synthesize all necessary molecules and proteins. Generally, scaffold materials for stem cell need to possess basic characteristics such as high porosity, large surface area, surface rigidity and biodegradability. Thus, the two-dimensional graphene oxide (GO) with oxygen-containing functional groups may be suitable scaffold materials for mesenchymal stem cell culture.MethodsIn this study, the effect of GO on the value-added differentiation activity of mesenchymal stem cell was systematically investigated. ResultsIt was found that low concentration of GO and sufficient concentration of umbilical cord mesenchymal stem cells are suitable for the second Co-culture. Furthermore, the addition of hyaluronic acid will make this culture more evenly distributed. ConclusionsThe adsorption of GO on umbilical cord mesenchymal stem cells can also make the two closely linked, which avoids the impact of animal joint activities on cells.

Download Full-text

Gene Therapy of Intracranial Glioma Using Interleukin 12–Secreting Human Umbilical Cord Blood–Derived Mesenchymal Stem Cells

Human Gene Therapy ◽

10.1089/hum.2010.187 ◽

2011 ◽

Vol 22 (6) ◽

pp. 733-743 ◽

Cited By ~ 89

Author(s):

Chung Heon Ryu ◽

Sang-Hoon Park ◽

Soon A Park ◽

Seong Muk Kim ◽

Jung Yeon Lim ◽

...

Keyword(s):

Stem Cells ◽

Gene Therapy ◽

Mesenchymal Stem Cells ◽

Cord Blood ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Interleukin 12 ◽

Human Umbilical Cord Blood ◽

Human Umbilical Cord

Download Full-text

Stem cell-based therapy for Parkinson’s disease with a focus on human endometrium-derived mesenchymal stem cells

Journal of Cellular Physiology ◽

10.1002/jcp.27182 ◽

2018 ◽

Vol 234 (2) ◽

pp. 1326-1335 ◽

Cited By ~ 12

Author(s):

Saeid Bagheri-Mohammadi ◽

Mohammad Karimian ◽

Behrang Alani ◽

Javad Verdi ◽

Rana Moradian Tehrani ◽

...

Keyword(s):

Parkinson’S Disease ◽

Stem Cells ◽

Parkinson's Disease ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Human Endometrium ◽

Cell Based Therapy

Download Full-text

A comprehensive cancer-associated microRNA expression profiling and proteomic analysis of human umbilical cord mesenchymal stem cell derived exosomes.

10.21203/rs.3.rs-1203367/v1 ◽

2021 ◽

Author(s):

Ganesan Jothimani ◽

Surajait Pathak ◽

Suman Dutta ◽

Asim K. Duttaroy ◽

Antara Banerjee

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Growth Factors ◽

Umbilical Cord ◽

Expression Patterns ◽

Functional Enrichment ◽

Human Umbilical Cord ◽

Human Mscs ◽

Anti Cancer

Abstract Background The mesenchymal stem cells (MSCs) have enormous therapeutic potential owing to their multi-lineage differentiation and self-renewal properties. MSCs express growth factors, cytokines, chemokines, and non-coding regulatory RNAs with immunosuppressive, anti-tumor, and migratory properties. MSCs also release several anti-cancer molecules via extracellular vesicles, that act as pro-apoptotic/tumor suppressor factors. This study aimed to identify the stem cell-derived secretome that could exhibit anti-cancer properties through molecular profiling of cargos in MSC-derived exosomes. Methods Human umbilical cord mesenchymal stem cells (hUCMSCs) were isolated from umbilical cord tissues and cultured expanded. After that, exosomes were isolated from the hUCMSC conditioned medium. The miRNA profiling of hUCMSCs and hUCMSC-derived exosomes was performed, followed by functional enrichment analysis. Results The miRNA expression profile and gene ontology (GO) depicts the differential expression patterns of high and less-expressed miRNAs that are delineated to be involved in the regulation of the apoptosis process. The LCMS/MS data and GO analysis indicate that hUCMSC secretomes are involved in several oncogenic and inflammatory signaling cascades. Conclusion Primary human MSCs releases miRNAs and growth factors via exosomes that are increasingly implicated in intercellular communications, and hUCMSC-exosomal miRNAs may have a critical influence in regulating cell death and apoptosis of cancer cells.

Download Full-text

Glutathione–Allylsulfur Conjugates as Mesenchymal Stem Cells Stimulating Agents for Potential Applications in Tissue Repair

International Journal of Molecular Sciences ◽

10.3390/ijms21051638 ◽

2020 ◽

Vol 21 (5) ◽

pp. 1638 ◽

Cited By ~ 1

Author(s):

Emilia Di Giovanni ◽

Silvia Buonvino ◽

Ivano Amelio ◽

Sonia Melino

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Tissue Repair ◽

Dermal Fibroblasts ◽

Water Soluble ◽

Dependent Manner ◽

Tissue Repair And Regeneration ◽

Stem Cell Delivery ◽

Cell Based Therapy

The endogenous gasotransmitter H2S plays an important role in the central nervous, respiratory and cardiovascular systems. Accordingly, slow-releasing H2S donors are powerful tools for basic studies and innovative pharmaco-therapeutic agents for cardiovascular and neurodegenerative diseases. Nonetheless, the effects of H2S-releasing agents on the growth of stem cells have not been fully investigated. H2S preconditioning can enhance mesenchymal stem cell survival after post-ischaemic myocardial implantation; therefore, stem cell therapy combined with H2S may be relevant in cell-based therapy for regenerative medicine. Here, we studied the effects of slow-releasing H2S agents on the cell growth and differentiation of cardiac Lin− Sca1+ human mesenchymal stem cells (cMSC) and on normal human dermal fibroblasts (NHDF). In particular, we investigated the effects of water-soluble GSH–garlic conjugates (GSGa) on cMSC compared to other H2S-releasing agents, such as Na2S and GYY4137. GSGa treatment of cMSC and NHDF increased their cell proliferation and migration in a concentration dependent manner with respect to the control. GSGa treatment promoted an upregulation of the expression of proteins involved in oxidative stress protection, cell–cell adhesion and commitment to differentiation. These results highlight the effects of H2S-natural donors as biochemical factors that promote MSC homing, increasing their safety profile and efficacy after transplantation, and the value of these donors in developing functional 3D-stem cell delivery systems for cardiac muscle tissue repair and regeneration.

Download Full-text

Systematic Intracellular Biocompatibility Assessments of Superparamagnetic Iron Oxide Nanoparticles in Human Umbilical Cord Mesenchyme Stem Cells in Testifying Its Reusability for Inner Cell Tracking by MRI

Journal of Biomedical Nanotechnology ◽

10.1166/jbn.2019.2845 ◽

2019 ◽

Vol 15 (11) ◽

pp. 2179-2192

Author(s):

Yuanyuan Xie ◽

Wei Liu ◽

Bing Zhang ◽

Bin Wang ◽

Liudi Wang ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Umbilical Cord ◽

Cell Tracking ◽

Superparamagnetic Iron Oxide ◽

Human Umbilical Cord ◽

Cell Based Therapy

Until now, there is no effective method for tracking transplanted stem cells in human. Ruicun (RC) is a new ultra-small SPIONs agent that has been approved by China Food and Drug Administration for iron supplementation but not as a stem cell tracer in clinic. In this study, we demonstrated magnetic resonance imaging-based tracking of RC-labeled human umbilical cord derived mesenchymal stem cells (MSCs) transplanted to locally injured site of rat spinal cords. We then comprehensively evaluated the safety and quality of the RC-labeled MSCs under good manufacturing practicecompliant conditions, to investigate the feasibility of SPIONs for inner tracking in stem cell-based therapy (SCT). Our results showed that RC labeling at appropriate dose (200 μg/mL) did not have evident impacts on characteristics of MSCs in vitro, demonstrating safety, non-carcinogenesis, and non-tissue inflammation in vivo. The systematic assessments of intracellular biocompatibility indicated that the RC labeled MSCs met with mandatory requirements and standards for law-regulation systems regarding SCT, facilitating translation of cell-tracking technologies to clinical trials.

Download Full-text