scholarly journals Intravenous Administration of Umbilical Cord Mesenchymal Stromal Cells in Advanced-stage Critical COVID-19: a Case Report

2020 ◽  
Author(s):  
Katia Nunes Silva ◽  
Priscila Pinheiro ◽  
Andre Gobatto ◽  
Rogerio Passos ◽  
Bruno Paredes ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Case Report ◽  
Umbilical Cord ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Prolonged Mechanical Ventilation ◽  
Invasive Mechanical Ventilation ◽  
Disease Patient ◽  
Human Umbilical Cord ◽  
Advanced Stage

Abstract Background: Coronavirus disease 2019 (COVID-19) associated- severe acute respiratory distress syndrome (ARDS) patients may require prolonged mechanical ventilation, thus resulting in lung fibrosis and high fatality rates. Several therapies have been developed in patients with pneumonia requiring oxygen therapy as well as during the early course of invasive mechanical ventilation. Mesenchymal stromal cells (MSCs) may have a role in controlling the hyperinflammatory response seen in such cases and prevent aggravation or increase/accelerate recovery. While MSC-based therapies have been studied mostly in patients that did not require invasive ventilation or during the first hours of tracheal intubation, to date the potential of MSC therapy to treat advanced-stage of severe/critical COVID-19 cases has not been extensively studied. Methods: This is a case report of a 30-year-old male patient who presented progressive clinical deterioration of COVID-19 in ICU after 21-day admission and 14 days with invasive mechanical ventilation. The first symptom onset was 35 days before MSC therapy. The patient was treated with allogenic human umbilical cord-derived MSCs [5 x 107 (2 doses 2 days interval)].Results: No serious adverse events attributed to MSC administration were observed during and after the procedure. Oxygenation (PaO2/FiO2 ratio) and the need for vasoactive drugs improved. Chest CT scan imaging, which showed signs of bilateral and peripheral ground-glass, consolidation as well as fibrosis, improved significantly during the time course of the disease. Patient was discharged 13 days after cell therapy. Cytokine analysis demonstrated modulation of different mediators accompanied by modulation of different cell populations in peripheral blood, including a reduction in inflammatory monocytes, increased frequency of patrolling monocytes, CD4+ lymphocytes and type 2 classical dendritic cells (cDC2). Conclusion: This study described for the first time the effects of MSC therapy in a patient at late stage COVID-19 associated severe lung injury and fibrosis. Therefore, further clinical trials should be design assessing the efficacy of MSC therapy in ARDS patients undergoing prolonged mechanical ventilation due to COVID-19.

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 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 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.

scholarly journals Locally Delivered Umbilical Cord Mesenchymal Stromal Cells Reduce Chronic Inflammation in Long-Term Nonhealing Wounds: A Randomized Study

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Yulia Suzdaltseva ◽  
Sergey Zhidkih ◽  
Sergey L. Kiselev ◽  
Victor Stupin
Keyword(s):  
Chronic Inflammation ◽  
Umbilical Cord ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Wound Repair ◽  
Chronic Wounds ◽  
Randomized Study ◽  
Biological Response ◽  
Regulatory Function ◽  
Human Umbilical Cord

Inflammation is part of a complex biological response to injury that mediates a rapid mobilization of cells and triggers the restoration of tissue homeostasis. The systemic diseases of the connective tissues, repetitive strain injuries, neuropathy, and vascular impairment lead to the development of a chronic inflammatory state. In such cases, a forced intervention is required to trigger tissue regeneration. Mesenchymal stromal cells (MSCs) have been considered a perspective tool for regenerative medicine because of their ability to change the expression and secretory profile under the influence of signals from the microenvironment to perform a regulatory function at the site of tissue damage. In this study, MSCs were isolated from the human umbilical cord (UCMSCs). The ability of UCMSCs to regulate chronic inflammation was investigated in a randomized placebo-controlled pilot study to assess the efficacy and safety of UCMSC therapy in patients with nonhealing wounds. A total of 108 patients with chronic wounds of different etiologies were randomly divided into two groups according to the criteria of inclusion and exclusion. The group (n=59) that was treated with a single local subcutaneous infusion of UCMSCs around the wound periphery showed a pronounced growth of granulation tissue, improved blood microcirculation, and reduction in wound size compared to the placebo group (n=49). No prominent adverse events were detected in patients from the UCMSC group during the 1-year follow-up period. This research has demonstrated that locally delivered allogeneic UCMSCs can contribute to chronic wound repair and provide an additional support toward new therapeutic strategies. Registration certificate №FS2006/341 was issued by the Federal Service for Surveillance in Healthcare.

Wharton’s Jelly Mesenchymal Stromal Cells from Human Umbilical Cord: a Close-up on Immunomodulatory Molecules Featured In Situ and In Vitro

2019 ◽  
Vol 15 (6) ◽  
pp. 900-918 ◽  
Author(s):  
Tiziana Corsello ◽  
Giandomenico Amico ◽  
Simona Corrao ◽  
Rita Anzalone ◽  
Francesca Timoneri ◽  
...  
Keyword(s):  
Umbilical Cord ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Wharton’S Jelly ◽  
Human Umbilical Cord ◽  
Wharton's Jelly
Sign in / Sign up

Export Citation Format

Share Document