Small molecule 2′-deoxycytidine differentiates human umbilical cord-derived MSCs into cardiac progenitors in vitro and their in vivo xeno-transplantation improves cardiac function

2020 ◽  
Vol 470 (1-2) ◽  
pp. 99-113 ◽  
Author(s):  
Syeda Roohina Ali ◽  
Waqas Ahmad ◽  
Nadia Naeem ◽  
Asmat Salim ◽  
Irfan Khan
Keyword(s):  
Cardiac Function ◽  
Umbilical Cord ◽  
Small Molecule ◽  
Human Umbilical Cord ◽  
Cardiac Progenitors

scholarly journals Microvesicles Derived from Human Umbilical Cord Mesenchymal Stem Cells Stimulated by Hypoxia Promote Angiogenesis Both In Vitro and In Vivo

2012 ◽  
Vol 21 (18) ◽  
pp. 3289-3297 ◽  
Author(s):  
Hong-Chao Zhang ◽  
Xin-Bin Liu ◽  
Shu Huang ◽  
Xiao-Yun Bi ◽  
Heng-Xiang Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Human Umbilical Cord

Abstract 1144: Successful Surface-Aminated Nanofiber Expansion of Human Umbilical Cord-Derived CD133+ Cells Leads to Augmentation of Angiogenic Functionality In Vitro and In Vivo

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Hiranmoy Das ◽  
Matthew Joseph ◽  
Nasreen Abdulhameed ◽  
Hai-Quan Mao ◽  
Vincent J Pompili
Keyword(s):  
Umbilical Cord ◽  
Hind Limb ◽  
Ex Vivo ◽  
Flow Cytometric Analysis ◽  
Surface Expression ◽  
Capillary Density ◽  
Therapeutic Angiogenesis ◽  
Human Umbilical Cord

Background: Umbilical cord blood (UCB) and marrow-derived CD133+ cells have been shown to mediate encouraging effects on therapeutic angiogenesis in both animal models and early clinical trials. Low numbers of CD133+ cells derived from a single donor have been a limitation of use of these cells in cardiovascular therapy. We hypothesized that an ex vivo aminated nanofiber system combined with cytokine supplementation would provide optimized topographical and biochemical signals to allow the expansion and potential functional augmentation of CD133+ cells without promoting terminal differentiation. Methods and Results: Human UCB derived CD133+ progenitor cells were isolated by MACS sorting and ex vivo expanded on aminated nanofiber plates with cytokine rich media. Cells harvested 10 days after expansion demonstrated a 225X increase in total number. Flow cytometric analysis demonstrated CD133–24%, CD34–93%, CXCR4–97%, LFA-97% surface expression. The expanded cells can uptake AcLDL efficiently and demonstrate a 2.3X increase in transwell migration to SDF-1 as compared to fresh UCB CD133+ cells. In vitro analysis revealed that expanded cells have potential to differentiate into endothelial or smooth muscle phenotype as demonstrated with CD31, vWF, VCAM-1 and F-pholloidin, α-actin, and SM myosin heavy chain immunocytochemistry when re-cultured for 14d in EGM2 or SMBM respectively. RT-QPCR analysis of 1% O 2 exposed (hypoxic) cells demonstrated a 2X increase in VEGF and 3X increase in IL-8 gene expression compared to normoxic control. In vivo functionality in a NOD/SCID mouse hind limb ischemic model demonstrated that mice treated with 5 x 10 6 expanded cells (n=7) augmented blood flow ratio (ischemic/control limb) as compared to mice treated with CD133+ cells (n=7) and control (n=7) at 28d. (control 0.32±.02 vs. UCB133+ 0.37±.02 vs. expanded cells 0.50±.04 p<0.01) Capillary density in ischemic hind-limb was increased at 28d (control 62.5±5.4 vs. expanded cell 97.6±2.5 p< 0.01) Conclusions: These studies demonstrate successful high level expansion of UCB derived CD133+ cells into functionally potent stem cells which have the capacity to differentiate into vascular cells and promote in vivo neovascularization.

scholarly journals Umbilical cord as a long-term source of activatable mesenchymal stromal cells for immunomodulation

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Anton Selich ◽  
Katharina Zimmermann ◽  
Michel Tenspolde ◽  
Oliver Dittrich-Breiholz ◽  
Constantin von Kaisenberg ◽  
...  
Keyword(s):  
Umbilical Cord ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Induction Time ◽  
Dna Barcode ◽  
Human Umbilical Cord ◽  
Time Points

Abstract Background Mesenchymal stromal cells (MSCs) are used in over 800 clinical trials mainly due to their immune inhibitory activity. Umbilical cord (UC), the second leading source of clinically used MSCs, is usually cut in small tissue pieces. Subsequent cultivation leads to a continuous outgrowth of MSC explant monolayers (MSC-EMs) for months. Currently, the first MSC-EM culture takes approximately 2 weeks to grow out, which is then expanded and applied to patients. The initiating tissue pieces are then discarded. However, when UC pieces are transferred to new culture dishes, MSC-EMs continue to grow out. In case the functional integrity of these cells is maintained, later induced cultures could also be expanded and used for cell therapy. This would drastically increase the number of available cells for each patient. To test the functionality of MSC-EMs from early and late induction time points, we compared the first cultures to those initiated after 2 months by investigating their clonality and immunomodulatory capacity. Methods We analyzed the clonal composition of MSC-EM cultures by umbilical cord piece transduction using integrating lentiviral vectors harboring genetic barcodes assessed by high-throughput sequencing. We investigated the transcriptome of these cultures by microarrays. Finally, the secretome was analyzed by multiplexed ELISAs, in vitro assays, and in vivo in mice. Results DNA barcode analysis showed polyclonal MSC-EMs even after months of induction cycles. A transcriptome and secretome analyses of early and late MSC cultures showed only minor changes over time. However, upon activation with TNF-α and IFN-γ, cells from both induction time points produced a multitude of immunomodulatory cytokines. Interestingly, the later induced MSC-EMs produced higher amounts of cytokines. To test whether the different cytokine levels were in a therapeutically relevant range, we used conditioned medium (CM) in an in vitro MLR and an in vivo killing assay. CM from late induced MSC-EMs was at least as immune inhibitory as CM from early induced MSC-EMs. Conclusion Human umbilical cord maintains a microenvironment for the long-term induction of polyclonal and immune inhibitory active MSCs for months. Thus, our results would offer the possibility to drastically increase the number of therapeutically applicable MSCs for a substantial amount of patients.

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

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.

Overexpression of FOXQ1 enhances anti-senescence and migration effects of human umbilical cord mesenchymal stem cells in vitro and in vivo

2018 ◽  
Vol 373 (2) ◽  
pp. 379-393 ◽  
Author(s):  
Tao Zhang ◽  
Pan Wang ◽  
Yanxia Liu ◽  
Jiankang Zhou ◽  
Zhenqing Shi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Human Umbilical Cord ◽  
And Migration

scholarly journals In VitroDifferentiation of First Trimester Human Umbilical Cord Perivascular Cells into Contracting Cardiomyocyte-Like Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Peter Szaraz ◽  
Matthew Librach ◽  
Leila Maghen ◽  
Farwah Iqbal ◽  
Tanya A. Barretto ◽  
...  
Keyword(s):  
Umbilical Cord ◽  
Cardiac Regeneration ◽  
First Trimester ◽  
Human Umbilical Cord ◽  
Perivascular Cells ◽  
Differentiation Potential ◽  
Mortality And Morbidity ◽  
Cardiomyogenic Differentiation

Myocardial infarction (MI) causes an extensive loss of heart muscle cells and leads to congestive heart disease (CAD), the leading cause of mortality and morbidity worldwide. Mesenchymal stromal cell- (MSC-) based cell therapy is a promising option to replace invasive interventions. However the optimal cell type providing significant cardiac regeneration after MI is yet to be found. The aim of our study was to investigate the cardiomyogenic differentiation potential of first trimester human umbilical cord perivascular cells (FTM HUCPVCs), a novel, young source of immunoprivileged mesenchymal stromal cells. Based on the expression of cardiomyocyte markers (cTnT, MYH6, SIRPA, and CX43) FTM and term HUCPVCs achieved significantly increased cardiomyogenic differentiation compared to bone marrow MSCs, while their immunogenicity remained significantly lower as indicated by HLA-A and HLA-G expression and susceptibility to T cell mediated cytotoxicity. When applying aggregate-based differentiation, FTM HUCPVCs showed increased aggregate formation potential and generated contracting cells within 1 week of coculture, making them the first MSC type with this ability. Our results indicate that young FTM HUCPVCs have superior cardiomyogenic potential coupled with beneficial immunogenic properties when compared to MSCs of older tissue sources, suggesting thatin vitropredifferentiation could be a potential strategy to increase their effectivenessin vivo.

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