Origin-Specific Adhesive Interactions of Mesenchymal Stem Cells with Platelets Influence Their Behavior After Infusion

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Origin-Specific Adhesive Interactions of Mesenchymal Stem Cells with Platelets Influence Their Behavior After Infusion. / Sheriff, Lozan; Alanazi, Asma; Ward, Lewis S. C.; Ward, Carl; Munir, Hafsa; Rayes, Julie; Alassiri, Mohammed; Watson, Steve P.; Newsome, Phil N.; Rainger, G. E.; Kalia, Neena; Frampton, Jon; Mcgettrick, Helen M.; Nash, Gerard B.

In: Stem Cells, 23.03.2018.

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@article{36db69b7a8bb422392fbde8b8c7622b3,
title = "Origin-Specific Adhesive Interactions of Mesenchymal Stem Cells with Platelets Influence Their Behavior After Infusion",
abstract = "We investigated the adhesive behavior of mesenchymal stem cells (MSC) in blood, which might influence their fate when infused as therapy. Isolated human bone marrow MSC (BMMSC) or umbilical cord MSC (UCMSC) adhered efficiently from flow to the matrix proteins, collagen, or fibronectin, but did not adhere to endothelial selectins. However, when suspended in blood, BMMSC no longer adhered to collagen, while UCMSC adhered along with many aggregated platelets. Neither MSC adhered to fibronectin from flowing blood, although the fibronectin surface did become coated with a platelet monolayer. UCMSC induced platelet aggregation in platelet rich plasma, and caused a marked drop in platelet count when mixed with whole human or mouse blood in vitro, or when infused into mice. In contrast, BMMSC did not activate platelets or induce changes in platelet count. Interestingly, isolated UCMSC and BMMSC both adhered to predeposited platelets. The differences in behavior in blood were attributable to expression of podoplanin (an activating ligand for the platelet receptor CLEC‐2), which was detected on UCMSC, but not BMMSC. Thus, platelets were activated when bound to UCMSC, but not BMMSC. Platelet aggregation by UCMSC was inhibited by recombinant soluble CLEC‐2, and UCMSC did not cause a reduction in platelet count when mixed with blood from mice deficient in CLEC‐2. We predict that both MSC would carry platelets in the blood, but their interaction with vascular endothelium would depend on podoplanin‐induced activation of the bound platelets. Such interactions with platelets might target MSC to damaged tissue, but could also be thrombotic.",
author = "Lozan Sheriff and Asma Alanazi and Ward, {Lewis S. C.} and Carl Ward and Hafsa Munir and Julie Rayes and Mohammed Alassiri and Watson, {Steve P.} and Newsome, {Phil N.} and Rainger, {G. E.} and Neena Kalia and Jon Frampton and Mcgettrick, {Helen M.} and Nash, {Gerard B.}",
year = "2018",
month = mar,
day = "23",
doi = "10.1002/stem.2811",
language = "English",
journal = "Stem Cells",
issn = "1066-5099",
publisher = "AlphaMed Press",

}

RIS

TY - JOUR

T1 - Origin-Specific Adhesive Interactions of Mesenchymal Stem Cells with Platelets Influence Their Behavior After Infusion

AU - Sheriff, Lozan

AU - Alanazi, Asma

AU - Ward, Lewis S. C.

AU - Ward, Carl

AU - Munir, Hafsa

AU - Rayes, Julie

AU - Alassiri, Mohammed

AU - Watson, Steve P.

AU - Newsome, Phil N.

AU - Rainger, G. E.

AU - Kalia, Neena

AU - Frampton, Jon

AU - Mcgettrick, Helen M.

AU - Nash, Gerard B.

PY - 2018/3/23

Y1 - 2018/3/23

N2 - We investigated the adhesive behavior of mesenchymal stem cells (MSC) in blood, which might influence their fate when infused as therapy. Isolated human bone marrow MSC (BMMSC) or umbilical cord MSC (UCMSC) adhered efficiently from flow to the matrix proteins, collagen, or fibronectin, but did not adhere to endothelial selectins. However, when suspended in blood, BMMSC no longer adhered to collagen, while UCMSC adhered along with many aggregated platelets. Neither MSC adhered to fibronectin from flowing blood, although the fibronectin surface did become coated with a platelet monolayer. UCMSC induced platelet aggregation in platelet rich plasma, and caused a marked drop in platelet count when mixed with whole human or mouse blood in vitro, or when infused into mice. In contrast, BMMSC did not activate platelets or induce changes in platelet count. Interestingly, isolated UCMSC and BMMSC both adhered to predeposited platelets. The differences in behavior in blood were attributable to expression of podoplanin (an activating ligand for the platelet receptor CLEC‐2), which was detected on UCMSC, but not BMMSC. Thus, platelets were activated when bound to UCMSC, but not BMMSC. Platelet aggregation by UCMSC was inhibited by recombinant soluble CLEC‐2, and UCMSC did not cause a reduction in platelet count when mixed with blood from mice deficient in CLEC‐2. We predict that both MSC would carry platelets in the blood, but their interaction with vascular endothelium would depend on podoplanin‐induced activation of the bound platelets. Such interactions with platelets might target MSC to damaged tissue, but could also be thrombotic.

AB - We investigated the adhesive behavior of mesenchymal stem cells (MSC) in blood, which might influence their fate when infused as therapy. Isolated human bone marrow MSC (BMMSC) or umbilical cord MSC (UCMSC) adhered efficiently from flow to the matrix proteins, collagen, or fibronectin, but did not adhere to endothelial selectins. However, when suspended in blood, BMMSC no longer adhered to collagen, while UCMSC adhered along with many aggregated platelets. Neither MSC adhered to fibronectin from flowing blood, although the fibronectin surface did become coated with a platelet monolayer. UCMSC induced platelet aggregation in platelet rich plasma, and caused a marked drop in platelet count when mixed with whole human or mouse blood in vitro, or when infused into mice. In contrast, BMMSC did not activate platelets or induce changes in platelet count. Interestingly, isolated UCMSC and BMMSC both adhered to predeposited platelets. The differences in behavior in blood were attributable to expression of podoplanin (an activating ligand for the platelet receptor CLEC‐2), which was detected on UCMSC, but not BMMSC. Thus, platelets were activated when bound to UCMSC, but not BMMSC. Platelet aggregation by UCMSC was inhibited by recombinant soluble CLEC‐2, and UCMSC did not cause a reduction in platelet count when mixed with blood from mice deficient in CLEC‐2. We predict that both MSC would carry platelets in the blood, but their interaction with vascular endothelium would depend on podoplanin‐induced activation of the bound platelets. Such interactions with platelets might target MSC to damaged tissue, but could also be thrombotic.

U2 - 10.1002/stem.2811

DO - 10.1002/stem.2811

M3 - Article

JO - Stem Cells

JF - Stem Cells

SN - 1066-5099

ER -