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Origin and Adhesive Behavior of MSCs may Influence their Therapeutic Application

Review of “Origin-specific adhesive interactions of mesenchymal stem cells with platelets influence their behaviour after infusion” from STEM CELLS by Stuart P. Atkinson

Therapeutic approaches that employ the delivery of mesenchymal stem cells (MSC) commonly employ intravenous injection, which then permits MSCs to begin to secrete paracrine-acting factors and to migrate towards their required site-of-action. The process by which MSCs cross the endothelial surfaces of vessels to reach damaged tissues remains to be fully characterized, although prior research has indicated that MSC bind to endothelial cells with low efficiency under normal circulatory conditions [1, 2] and that recruitment may require the interaction of MSCs with platelets [3]. 

Now, a team of researchers led by Gerard B. Nash (University of Birmingham, UK) report in STEM CELLS that the site of origin of MSCs and their inherent adhesive capabilities may significantly influence their therapeutic application [4].  

Sheriff et al. initially discovered that flowing [5] human bone marrow MSCs (BM-MSCs) or umbilical cord MSCs (UC-MSCs) efficiently adhered to matrix proteins and components of damaged vessel walls (collagen and fibronectin via 1 and 3 integrins), but did not adhere to receptors presented by activated platelets or inflamed endothelium (endothelial selectins).  However, perfusion in the presence of whole blood led to significant alterations: BM-MSCs no longer adhered to collagen, UC-MSCs adhered to collagen alongside aggregated platelets, and neither MSC-type adhered to fibronectin (the fibronectin surface presented with a platelet monolayer).

While BM-MSCs bound platelets, they did not activate platelets or induce changes to platelet count. Additionally, UC-MSCs induced platelet aggregation in platelet-rich plasma and caused a marked drop in platelet count, with this ability linked to the UC-MSC-specific expression of podoplanin, an activating ligand for the platelet receptor CLEC‐2. In confirmation of this link, recombinant soluble CLEC‐2 inhibited platelet aggregation by UC-MSC, and the combination of UCMSCs with blood from mice deficient in CLEC‐2 did not reduce platelet count.

The authors posit that these findings may hold significant therapeutic relevance: interactions of platelets may allow MSCs to target damaged tissues efficiently; however, podoplanin-expression on specific MSC types may also lead to clotting or reduced platelet numbers and the associated side effects.

For more on how the origin and adhesive behavior of MSCs may influence their therapeutic application, stay tuned to the Stem Cells Portal!


  1. Newman RE, Yoo D, LeRoux MA, et al., Treatment of inflammatory diseases with mesenchymal stem cells. Inflamm Allergy Drug Targets 2009;8:110-23.
  2. Segers VF, Van Riet I, Andries LJ, et al., Mesenchymal stem cell adhesion to cardiac microvascular endothelium: activators and mechanisms. Am J Physiol Heart Circ Physiol 2006;290:H1370-7.
  3. Teo GS, Yang Z, Carman CV, et al., Intravital imaging of mesenchymal stem cell trafficking and association with platelets and neutrophils. Stem Cells 2015;33:265-77.
  4. Sheriff L, Alanazi A, Ward LSC, et al., Origin-Specific Adhesive Interactions of Mesenchymal Stem Cells with Platelets Influence Their Behavior After Infusion. STEM CELLS 2018;36:1062-1074.
  5. Thin LN, McGettrick HM, Buckley CD, et al., Crosstalk Between Mesenchymal Stem Cells and Endothelial Cells Leads to Downregulation of Cytokine‐Induced Leukocyte Recruitment. STEM CELLS 2013;31:2690-2702.