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

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.

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Human Umbilical Cord Perivascular Cells and Human Bone Marrow Mesenchymal Stromal Cells Transplanted Intramuscularly Respond to a Distant Source of Inflammation

Stem Cells and Development ◽

10.1089/scd.2017.0248 ◽

2018 ◽

Vol 27 (6) ◽

pp. 415-429 ◽

Cited By ~ 10

Author(s):

Shiva Hamidian Jahromi ◽

Catalina Estrada ◽

Yunqing Li ◽

Elaine Cheng ◽

John E. Davies

Keyword(s):

Bone Marrow ◽

Umbilical Cord ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Human Bone ◽

Human Bone Marrow ◽

Human Umbilical Cord ◽

Distant Source ◽

Perivascular Cells

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Human umbilical cord mesenchymal stromal cells promote the regeneration of severe endometrial damage in a rat model

Acta Biochimica et Biophysica Sinica ◽

10.3724/abbs.2021015 ◽

2021 ◽

Author(s):

Mei Zhuang ◽

Wuwen Zhang ◽

Nuo Cheng ◽

Ling Zhou ◽

Dan Liu ◽

...

Keyword(s):

Umbilical Cord ◽

Mesenchymal Stromal Cells ◽

Rat Model ◽

Stromal Cells ◽

Human Umbilical Cord

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

Stem Cell Research & Therapy ◽

10.1186/s13287-019-1376-9 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 4

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.

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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

Cell Transplantation ◽

10.1177/0963689720945677 ◽

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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A novel combination cell therapy using first trimester human umbilical cord-derived mesenchymal stromal cells and endothelial progenitor cells significantly improves cardiac recovery after myocardial infarction

Cytotherapy ◽

10.1016/j.jcyt.2019.03.455 ◽

2019 ◽

Vol 21 (5) ◽

pp. S67

Author(s):

F. Iqbal ◽

A. Johnston ◽

B. Wyse ◽

P. Mander ◽

J. Wu ◽

...

Keyword(s):

Myocardial Infarction ◽

Cell Therapy ◽

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Umbilical Cord ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

First Trimester ◽

Human Umbilical Cord ◽

Cardiac Recovery

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

Stem Cells International ◽

10.1155/2020/5308609 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11 ◽

Cited By ~ 1

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.

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