scholarly journals Long-Term Efficacy and Safety of Human Umbilical Cord Mesenchymal Stromal Cells in Rotenone-Induced Hemiparkinsonian Rats

2010 ◽  
Vol 16 (11) ◽  
pp. 1519-1529 ◽  
Author(s):  
Nian Xiong ◽  
Xuebing Cao ◽  
Zhentao Zhang ◽  
Jinsha Huang ◽  
Chunnuan Chen ◽  
...  
Keyword(s):  
Umbilical Cord ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Human Umbilical Cord ◽  
Efficacy And Safety ◽  
Term Efficacy

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.

scholarly journals Consistent Long-Term Therapeutic Efficacy of Human Umbilical Cord Matrix-Derived Mesenchymal Stromal Cells After Myocardial Infarction Despite Individual Differences and Transient Engraftment

2021 ◽  
Vol 9 ◽  
Author(s):  
Tiago L. Laundos ◽  
Francisco Vasques-Nóvoa ◽  
Rita N. Gomes ◽  
Vasco Sampaio-Pinto ◽  
Pedro Cruz ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Umbilical Cord ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Cardiac Remodeling ◽  
Human Umbilical Cord ◽  
Therapeutic Benefits ◽  
Umbilical Cord Matrix

Human mesenchymal stem cells gather special interest as a universal and feasible add-on therapy for myocardial infarction (MI). In particular, human umbilical cord matrix-derived mesenchymal stromal cells (UCM-MSC) are advantageous since can be easily obtained and display high expansion potential. Using isolation protocols compliant with cell therapy, we previously showed UCM-MSC preserved cardiac function and attenuated remodeling 2 weeks after MI. In this study, UCM-MSC from two umbilical cords, UC-A and UC-B, were transplanted in a murine MI model to investigate consistency and durability of the therapeutic benefits. Both cellular products improved cardiac function and limited adverse cardiac remodeling 12 weeks post-ischemic injury, supporting sustained and long-term beneficial therapeutic effect. Donor associated variability was found in the modulation of cardiac remodeling and activation of the Akt-mTOR-GSK3β survival pathway. In vitro, the two cell products displayed similar ability to induce the formation of vessel-like structures and comparable transcriptome in normoxia and hypoxia, apart from UCM-MSCs proliferation and expression differences in a small subset of genes associated with MHC Class I. These findings support that UCM-MSC are strong candidates to assist the treatment of MI whilst calling for the discussion on methodologies to characterize and select best performing UCM-MSC before clinical application.

scholarly journals Therapeutic effect of human umbilical cord-derived multipotent mesenchymal stromal cells in a patient with Crigler–Najjar syndrome type I

2019 ◽  
Vol 64 (4) ◽  
pp. 26-34
Author(s):  
G. T. Sukhikh ◽  
A. V. Degtyareva ◽  
D. N. Silachev ◽  
K. V. Gorunov ◽  
I. V. Dubrovina ◽  
...  
Keyword(s):  
Umbilical Cord ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Human Umbilical Cord ◽  
Type I ◽  
Syndrome Type ◽  
Safe Level ◽  
Period 2

The article presents the results of intravenous transplantation of allogeneic multipotent mesenchymal stromal cells, derived from a human umbilical cord, to a child with Crigler–Najjarsyndrome type I during the first 2 years of life. The therapy is aimed at reduction of the duration of phototherapy while maintaining a safe level of serum bilirubin.In this study, a five-day-old child with the bilirubin level of 340 µmol/l was treated with phototherapy for 16–18 hours daily in the neonatal period. Then, phototherapy was reduced to 14–16 hours. The level of bilirubin varied from 329 to 407 μmol/l. At the age of 2 months, it was decided to use multipotent mesenchymal stromal cells with a significant decrease in the duration of phototherapy up to 2 hours a day. During the observation period (2 years at the time of writing this article) the child received 6 injections of multipotent mesenchymal stromal cells. A positive effect developed within 4–7 days after administration and persisted for 2–3 months. There were no side effects or complications during and after transplantation.Thus, intravenous transplantation of multipotent mesenchymal stromal cells is an effective treatment of Crigler–Najjar syndrome type I; it reducesthe need for phototherapy,significantly improvesthe quality of life of the patients and prolongstheir life with native liver. 

High yield of human umbilical cord-derived mesenchymal stromal cells in an animal component-free culture medium

Cytotherapy ◽  
2020 ◽  
Vol 22 (5) ◽  
pp. S111-S112
Author(s):  
R. Wagey ◽  
K. Bertram ◽  
M. Elliott ◽  
A. Eaves ◽  
S. Szilvassy ◽  
...  
Keyword(s):  
Umbilical Cord ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Culture Medium ◽  
High Yield ◽  
Human Umbilical Cord ◽  
Animal Component

scholarly journals Extracellular Vesicles Derived from Human Umbilical Cord Mesenchymal Stromal Cells Protect Cardiac Cells Against Hypoxia/Reoxygenation Injury by Inhibiting Endoplasmic Reticulum Stress via Activation of the PI3K/Akt Pathway

2020 ◽  
Vol 29 ◽  
pp. 096368972094567
Author(s):  
Changyi Zhang ◽  
Hongwu Wang ◽  
Godfrey C.F. Chan ◽  
Yu Zhou ◽  
Xiulan Lai ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Umbilical Cord ◽  
Extracellular Vesicles ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Cardiac Cells ◽  
Akt Pathway ◽  
Human Umbilical Cord ◽  
Hypoxia Reoxygenation

Endoplasmic reticulum (ER) stress is implicated in the pathogenesis of many diseases, including myocardial ischemia/reperfusion injury. We hypothesized that human umbilical cord mesenchymal stromal cells derived extracellular vesicles (HuMSC-EVs) could protect cardiac cells against hyperactive ER stress induced by hypoxia/reoxygenation (H/R) injury. The H/R model was generated using the H9c2 cultured cardiac cell line. HuMSC-EVs were extracted using a commercially available exosome isolation reagent. Levels of apoptosis-related signaling molecules and the degree of ER stress were assessed by western blot. The role of the PI3K/Akt pathway was investigated using signaling inhibitors. Lactate dehydrogenase leakage and 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) analysis were used for evaluating the therapeutic effects of HuMSC-EVs in vitro. The results showed that ER stress and the rate of apoptosis were increased in the context of H/R injury. Treatment with HuMSC-EVs inhibited ER stress and increased survival in H9c2 cells exposed to H/R. Mechanistically, the PI3K/Akt pathway was activated by treatment with HuMSC-EVs after H/R. Inhibition of the PI3K/Akt pathway by a specific inhibitor, LY294002, partially reduced the protective effect of HuMSC-EVs. Our findings suggest that HuMSC-EVs could alleviate ER stress–induced apoptosis during H/R via activation of the PI3K/Akt pathway.

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