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Procoagulant activity of human mesenchymal stem cells.
J Trauma Acute Care Surg 2017; 83(1 Suppl 1):S164-S169JT

Abstract

BACKGROUND

Allogeneic mesenchymal stem cells (MSCs) show great potential for the treatment of military and civilian trauma based on their reduced immunogenicity and ability to modulate inflammation and immune function in the recipient. Although generally considered to be safe, MSCs express tissue factor (TF), a potent activator of coagulation. In the current study, we evaluated multiple MSC populations for tissue factor expression and procoagulant activity to characterize safety considerations for systemic use of MSCs in trauma patients who may have altered coagulation homeostasis.

METHODS

Multiple MSC populations derived from either human adipose tissue or bone marrow were expanded in the recommended stem cell media. Stem cell identity was confirmed using a well-characterized panel of positive and negative markers. Tissue factor expression on the cell surface was evaluated by flow cytometry with anti-CD142 antibody. Effects on blood coagulation were determined by thromboelastography and calibrated automated thrombogram assays using platelet-poor plasma or whole blood.

RESULTS

Mesenchymal stem cells express tissue factor on their surfaces and are procoagulant in the presence of blood or plasma. The adipose-derived MSCs (Ad-MSC) evaluated were more procoagulant and expressed more tissue factor than bone marrow MSCs (BM-MSCs), which showed a greater variability in TF expression. Bone marrow MSCs were identified that exhibited low procoagulant activity, whereas all Ad-MSCs examined exhibited high procoagulant activity. The percentage of cells in a given population expressing surface tissue factor correlates roughly with functional procoagulant activity. Mesenchymal stem cell tissue factor expression and procoagulant activity change over time in culture.

CONCLUSIONS

All MSC populations are not equivalent; care should be taken to select cells for clinical use that minimize potential safety problems and maximize chance of patient benefit. Adipose-derived MSCs seem more consistently procoagulant than BM-MSCs, presenting a potential safety concern for systemic administration in coagulopathic patients. Donor variation exists between different cell populations, and culture handling conditions may also determine coagulation activity. Cells must be routinely monitored during preparation to ensure that they retain the desired characteristics before patient administration.

Authors+Show Affiliations

From the Coagulation & Blood Research (B.A.C., M.C.H., R.K.M., C.D., J.A.B., K.M.R., A.P.C.), US Army Institute of Surgical Research, JBSA Fort Sam Houston, Texas; Department of Molecular Medicine (B.A.C.), University of Texas Health Science Center at San Antonio, San Antonio, Texas, and Department of Surgery (A.P.C.), University of Texas Health Science Center at San Antonio, San Antonio, Texas.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

28628602

Citation

Christy, Barbara A., et al. "Procoagulant Activity of Human Mesenchymal Stem Cells." The Journal of Trauma and Acute Care Surgery, vol. 83, no. 1 Suppl 1, 2017, pp. S164-S169.
Christy BA, Herzig MC, Montgomery RK, et al. Procoagulant activity of human mesenchymal stem cells. J Trauma Acute Care Surg. 2017;83(1 Suppl 1):S164-S169.
Christy, B. A., Herzig, M. C., Montgomery, R. K., Delavan, C., Bynum, J. A., Reddoch, K. M., & Cap, A. P. (2017). Procoagulant activity of human mesenchymal stem cells. The Journal of Trauma and Acute Care Surgery, 83(1 Suppl 1), pp. S164-S169. doi:10.1097/TA.0000000000001485.
Christy BA, et al. Procoagulant Activity of Human Mesenchymal Stem Cells. J Trauma Acute Care Surg. 2017;83(1 Suppl 1):S164-S169. PubMed PMID: 28628602.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Procoagulant activity of human mesenchymal stem cells. AU - Christy,Barbara A, AU - Herzig,Maryanne C, AU - Montgomery,Robbie K, AU - Delavan,Christopher, AU - Bynum,James A, AU - Reddoch,Kristin M, AU - Cap,Andrew P, PY - 2017/6/20/entrez PY - 2017/6/20/pubmed PY - 2017/8/31/medline SP - S164 EP - S169 JF - The journal of trauma and acute care surgery JO - J Trauma Acute Care Surg VL - 83 IS - 1 Suppl 1 N2 - BACKGROUND: Allogeneic mesenchymal stem cells (MSCs) show great potential for the treatment of military and civilian trauma based on their reduced immunogenicity and ability to modulate inflammation and immune function in the recipient. Although generally considered to be safe, MSCs express tissue factor (TF), a potent activator of coagulation. In the current study, we evaluated multiple MSC populations for tissue factor expression and procoagulant activity to characterize safety considerations for systemic use of MSCs in trauma patients who may have altered coagulation homeostasis. METHODS: Multiple MSC populations derived from either human adipose tissue or bone marrow were expanded in the recommended stem cell media. Stem cell identity was confirmed using a well-characterized panel of positive and negative markers. Tissue factor expression on the cell surface was evaluated by flow cytometry with anti-CD142 antibody. Effects on blood coagulation were determined by thromboelastography and calibrated automated thrombogram assays using platelet-poor plasma or whole blood. RESULTS: Mesenchymal stem cells express tissue factor on their surfaces and are procoagulant in the presence of blood or plasma. The adipose-derived MSCs (Ad-MSC) evaluated were more procoagulant and expressed more tissue factor than bone marrow MSCs (BM-MSCs), which showed a greater variability in TF expression. Bone marrow MSCs were identified that exhibited low procoagulant activity, whereas all Ad-MSCs examined exhibited high procoagulant activity. The percentage of cells in a given population expressing surface tissue factor correlates roughly with functional procoagulant activity. Mesenchymal stem cell tissue factor expression and procoagulant activity change over time in culture. CONCLUSIONS: All MSC populations are not equivalent; care should be taken to select cells for clinical use that minimize potential safety problems and maximize chance of patient benefit. Adipose-derived MSCs seem more consistently procoagulant than BM-MSCs, presenting a potential safety concern for systemic administration in coagulopathic patients. Donor variation exists between different cell populations, and culture handling conditions may also determine coagulation activity. Cells must be routinely monitored during preparation to ensure that they retain the desired characteristics before patient administration. SN - 2163-0763 UR - https://www.unboundmedicine.com/medline/citation/28628602/Procoagulant_activity_of_human_mesenchymal_stem_cells_ L2 - http://Insights.ovid.com/pubmed?pmid=28628602 DB - PRIME DP - Unbound Medicine ER -