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

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. In this study, 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 hemocompatibility, 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, for example, 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.

Placenta-Derived Decidua Stromal Cells for Hemorrhagic Cystitis after Stem Cell Transplantation

“…Because DSCs induce coagulation more effectively than BM-MSCs, they were selected for the treatment of HC in this pilot study [26]. …”

“…Both BM-MSCs and Wharton jelly-derived MSCs have shown promising results [16,19,21,41]. There are several theoretical advantages to using DSCs over BM-MSCs for HC, such as smaller size, better coagulation capacity, less differentiation to cartilage and bone, and an increased expression of integrins that may facilitate migration to inflamed tissue [25,26,28]. …”

“…The DSCs are immunosuppressive in vitro, and they express surface markers that are important for homing to inflamed tissues [24,25]. DSCs differ from bone marrow (BM)-MSCs in several aspects: they are half the size, more immunosuppressive, need direct contact to show the immunomodulatory effect, have a better expansion capacity, and do not differentiate well to cartilage and bone [24,25,26]. We have used DSCs after HSCT to treat severe acute GVHD, chronic GVHD, and acute respiratory distress syndrome, with positive responses in the vast majority of patients [27,28,29].…”

“…We have used DSCs after HSCT to treat severe acute GVHD, chronic GVHD, and acute respiratory distress syndrome, with positive responses in the vast majority of patients [27,28,29]. There are also in vitro data to suggest that DSCs promote clotting, which is in line with the fast recovery after postpartum hemorrhaging [26]. In this study, we wanted to find an optimal treatment for HC using DSCs, to be able to continue with a prospective double-blind, placebo-controlled study and test the possible efficacy.…”

Mesenchymal stromal cell therapy for the treatment of intestinal ischemia: Defining the optimal cell isolate for maximum therapeutic benefit

“…In addition to having the greatest isolation efficacy, WJ-MSCs also have the greatest expansion potential, suggesting that they may be the optimal birth-associated tissue MSC isolate with regards to ease of clinical translation (126). Placental MSCs may also have a slightly higher procoagulation effect (127), which may not be useful in the setting of an already ischemic intestine. Aside from differences in isolation efficacy, expansion potential, and coagulation profiles, all birth-associated tissue MSCs appear to have similar properties with regards to differentiation potential and immunosuppressive capabilities, suggesting that all of these cell isolates have the potential to attenuate intestinal ischemia and reperfusion injuries.…”