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Different Procoagulant Activity of Therapeutic Mesenchymal Stromal Cells Derived from Bone Marrow and Placental Decidua.

Moll, Guido; Ignatowicz, Lech LU ; Catar, Rusan; Luecht, Christian; Sadeghi, Behnam; Hamad, Osama; Jungebluth, Philipp; Dragun, Duska; Schmidtchen, Artur LU and Ringden, Olle (2015) In Stem Cells and Development 24(19). p.2269-2279
Abstract
While therapeutic mesenchymal stromal/stem cells (MSCs) have usually been obtained from bone marrow, perinatal tissues have emerged as promising new sources of cells for stromal cell therapy. Here we present a first safety follow-up on our clinical experience with placenta-derived decidual stromal cells (DSCs), used as supportive immunomodulatory and regenerative therapy for patients with severe complications after allogeneic hematopoietic stem cell transplantation (HSCT). We found that DSCs are smaller, almost half the volume of MSCs, which may favor microvascular passage. DSCs also show different hemo¬compatibility, with increased triggering of the clotting cascade after exposure to human blood and plasma in vitro. After infusion of DSCs... (More)
While therapeutic mesenchymal stromal/stem cells (MSCs) have usually been obtained from bone marrow, perinatal tissues have emerged as promising new sources of cells for stromal cell therapy. Here we present a first safety follow-up on our clinical experience with placenta-derived decidual stromal cells (DSCs), used as supportive immunomodulatory and regenerative therapy for patients with severe complications after allogeneic hematopoietic stem cell transplantation (HSCT). We found that DSCs are smaller, almost half the volume of MSCs, which may favor microvascular passage. DSCs also show different hemo¬compatibility, with increased triggering of the clotting cascade after exposure to human blood and plasma in vitro. After infusion of DSCs in HSCT patients, we observed a weak activation of the fibrinolytic system, but the other blood activation markers remained stable, excluding major adverse events. Expression profiling identified differential levels of key factors implicated in regulation of hemostasis, such as a lack of prostacyclin synthase and increased tissue factor expression in DSCs, suggesting that these cells have intrinsic blood-activating properties. The stronger triggering of the clotting cascade by DSCs could be antagonized by optimizing the cell graft reconstitution before infusion, e.g. by use of low-dose heparin anticoagulant in the cell infusion buffer. We conclude that DSCs are smaller and have stronger hemostatic properties than MSCs, thus triggering stronger activation of the clotting system, which can be antagonized by optimizing the cell graft preparation before infusion. Our results highlight the importance of hemocompatibility safety testing for every novel cell therapy product before clinical use, when applied using systemic delivery. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Stem Cells and Development
volume
24
issue
19
pages
2269 - 2279
publisher
Mary Ann Liebert, Inc.
external identifiers
  • pmid:26192403
  • wos:000361395900005
  • scopus:84941901159
ISSN
1557-8534
DOI
10.1089/scd.2015.0120
language
English
LU publication?
yes
id
af8a11a4-cbd0-41a4-be29-a713ac3f2c8b (old id 7733195)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26192403?dopt=Abstract
date added to LUP
2015-08-10 11:36:19
date last changed
2017-07-30 03:19:53
@article{af8a11a4-cbd0-41a4-be29-a713ac3f2c8b,
  abstract     = {While therapeutic mesenchymal stromal/stem cells (MSCs) have usually been obtained from bone marrow, perinatal tissues have emerged as promising new sources of cells for stromal cell therapy. Here we present a first safety follow-up on our clinical experience with placenta-derived decidual stromal cells (DSCs), used as supportive immunomodulatory and regenerative therapy for patients with severe complications after allogeneic hematopoietic stem cell transplantation (HSCT). We found that DSCs are smaller, almost half the volume of MSCs, which may favor microvascular passage. DSCs also show different hemo¬compatibility, with increased triggering of the clotting cascade after exposure to human blood and plasma in vitro. After infusion of DSCs in HSCT patients, we observed a weak activation of the fibrinolytic system, but the other blood activation markers remained stable, excluding major adverse events. Expression profiling identified differential levels of key factors implicated in regulation of hemostasis, such as a lack of prostacyclin synthase and increased tissue factor expression in DSCs, suggesting that these cells have intrinsic blood-activating properties. The stronger triggering of the clotting cascade by DSCs could be antagonized by optimizing the cell graft reconstitution before infusion, e.g. by use of low-dose heparin anticoagulant in the cell infusion buffer. We conclude that DSCs are smaller and have stronger hemostatic properties than MSCs, thus triggering stronger activation of the clotting system, which can be antagonized by optimizing the cell graft preparation before infusion. Our results highlight the importance of hemocompatibility safety testing for every novel cell therapy product before clinical use, when applied using systemic delivery.},
  author       = {Moll, Guido and Ignatowicz, Lech and Catar, Rusan and Luecht, Christian and Sadeghi, Behnam and Hamad, Osama and Jungebluth, Philipp and Dragun, Duska and Schmidtchen, Artur and Ringden, Olle},
  issn         = {1557-8534},
  language     = {eng},
  number       = {19},
  pages        = {2269--2279},
  publisher    = {Mary Ann Liebert, Inc.},
  series       = {Stem Cells and Development},
  title        = {Different Procoagulant Activity of Therapeutic Mesenchymal Stromal Cells Derived from Bone Marrow and Placental Decidua.},
  url          = {http://dx.doi.org/10.1089/scd.2015.0120},
  volume       = {24},
  year         = {2015},
}