Homing of Mesenchymal Stem Cells

Abstract

Mesenchymal stem cells (MSCs) are primarily fibroblast-like cells. Yet, once studied under conditions of shear stress when flowing along endothelial cells in vitro or in blood vessels, as well as in classic migration assays such as chemotaxis assays, MSCs have recently been found to function similarly to leukocytes in many ways. Firstly, MSCs express several homing receptors which are typically activated during extravasation of leukocytes. Secondly, some of these receptors are definitely functional, and required for their tissue localization in certain physiological or pathological contexts. Clinical protocols have in the last few years provided the first data on whether and how human MSCs may work in patients once delivered locally e.g. by injection, or systemically via the intra-arterial or intravenous route. Still, analysis of the ability of MSCs to activate specific homing receptors has up to now received relatively little attention. Moreover, maintenance or alterations of homing receptor expression or functions during good manufacturing practice (GMP) preparation steps, and documentation of presence and function of individual pathways on MSC preparations for clinical use are often missed. Hence, we review here mechanisms predicted to be relevant for adhesion, migration, and homing competence of MSCs. We also discuss some early data on homing of MSCs, deduced from preclinical experiments and from the few clinical studies with MSCs. Finally, we introduce some assays which could be applied to monitor preservation of the homing capacity of MSCs during GMP preparation.

Mesenchymal stem cells in tumor development

“…The identification of the adhesion molecules and surface receptors that guide the vascular adhesion of MSCs has been aided by comparisons to the similar activities of HSCs and leukocytes (reviewed in ref. 115). Like hematopoietic cells, MSCs appear to utilize E-selectin for vascular adhesion, but lack other hematopoietic cell adhesion molecules such as L-selectin, β2 integrins and platelet endothelial cell adhesion molecule-1 (PECAM-1)/CD34 that facilitate the rolling of HSCs on vasculature and their subsequent transmigration through the endothelial wall.…”

Mechanism of arterial remodeling in chronic allograft vasculopathy

“…They found that CD44 in stem cells enables them to bind to E-selectin [43]. Other molecules and chemokines that are involved in migration of stem cells to sites of damaged tissue are VCAM-1, ICAM-1, ICAM-2, transforming growth factor-β (TGF-β) and MCP-1 [27,44]. The amount of host-derived stem cells contributing to graft neointima has not been assessed accurately.…”

The Therapeutic Potential of Stimulating Endogenous Stem Cell Mobilization

“…The process of PBSC recruitment in a tissue takes place predominantly at the level the postcapillary venule, in a manner similar to neutrophils (Henschler et al, 2008).…”