A Protocol for the Isolation, Culture, and Cryopreservation of Umbilical Cord-Derived Canine Mesenchymal Stromal Cells: Role of Cell Attachment in Long-Term Maintenance

2020 ◽  
Vol 29 (11) ◽  
pp. 695-713 ◽  
Author(s):  
Adrienne Wright ◽  
Larry Snyder ◽  
Kaori Knights ◽  
Hong He ◽  
Nora L. Springer ◽  
...  
Keyword(s):  
Umbilical Cord ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Cell Attachment ◽  
Term Maintenance

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.

Role of CD271 enrichment in the isolation of mesenchymal stromal cells from umbilical cord blood

2013 ◽  
Vol 37 (9) ◽  
pp. 1010-1015 ◽  
Author(s):  
Armin Attar ◽  
Arash Ghalyanchi Langeroudi ◽  
Attyieh Vassaghi ◽  
Iman Ahrari ◽  
Mohsen Khosravi Maharlooei ◽  
...  
Keyword(s):  
Cord Blood ◽  
Umbilical Cord ◽  
Mesenchymal Stromal Cells ◽  
Umbilical Cord Blood ◽  
Stromal Cells

The expression and role of miR-301a in human umbilical cord-derived mesenchymal stromal cells

Cytotherapy ◽  
2013 ◽  
Vol 15 (12) ◽  
pp. 1511-1516 ◽  
Author(s):  
Fengxia Ma ◽  
Dandan Chen ◽  
Ying Chi ◽  
Fang Chen ◽  
Xue Li ◽  
...  
Keyword(s):  
Umbilical Cord ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Human Umbilical Cord

scholarly journals Long term maintenance of myeloid leukemic stem cells cultured with unrelated human mesenchymal stromal cells

2015 ◽  
Vol 14 (1) ◽  
pp. 95-104 ◽  
Author(s):  
Sawa Ito ◽  
A. John Barrett ◽  
Amalia Dutra ◽  
Evgenia Pak ◽  
Samantha Miner ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Leukemic Stem Cells ◽  
Human Mesenchymal Stromal Cells ◽  
Term Maintenance ◽  
Cells Cultured

Expression and role of Toll-like receptors on human umbilical cord mesenchymal stromal cells

Cytotherapy ◽  
2013 ◽  
Vol 15 (4) ◽  
pp. 423-433 ◽  
Author(s):  
Dandan Chen ◽  
Fengxia Ma ◽  
Shuxia Xu ◽  
Shaoguang Yang ◽  
Fang Chen ◽  
...  
Keyword(s):  
Umbilical Cord ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Human Umbilical Cord ◽  
Toll Like Receptors

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 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.

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