title: Role of progenitor cells in transplant arteriosclerosis.
abstract: To date, chronic transplant dysfunction (CTD) is recognized as the major cause of transplant loss long term after transplantation. CTD has the remarkable histologic feature that the luminal areas of the intragraft arteries become obliterated as a result of occlusive neointima formation. Neointimal lesions contain predominantly vascular smooth muscle cells (VSMCs) and extracellular matrix admixed with inflammatory cells. At the luminal side, neointimal lesions are covered with a monolayer of endothelial cells (ECs). The etiology of transplant arteriosclerosis (TA) is largely unknown, and adequate prevention and treatment protocols are not available. In contrast to the largely accepted "response-to-injury" hypothesis for the development of TA that attributes an important role to graft-derived ECs and VSMCs, recent data indicate that host-derived vascular progenitor cells play a major role in the development of TA. The process leading to TA appears to be heterogeneous, and neointimal ECs and VSMCs can be recruited from different sources, possibly depending on the severity and duration of vascular damage. These data suggest a significant role of host-derived circulating EC/VSMC progenitor cells, which may be partly bone marrow derived. Circulating vascular progenitor cells are potential targets for therapeutic intervention to ameliorate TA development. Therefore, identification of mediators and cellular mechanisms that promote recruitment of vascular progenitors to sites of injury is warranted to dissect their detrimental and possible beneficial effects in the development of TA.
authors.affiliation: Department of Cell Biology, Section Immunology & Histology, University Medical Center Groningen, A. Deusinglaan 1, NL-9713 AV Groningen, The Netherlands. j.l.hillebrands@med.rug.nl
authors.forename: Jan-Luuk
authors.initials: JL
authors.lastname: Hillebrands
authors.forename: Geanina
authors.initials: G
authors.lastname: Onuta
authors.forename: Jan
authors.initials: J
authors.lastname: Rozing
mesh_terms: D049109:Cell Proliferation; D003324:Coronary Artery Disease / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism*; D006085:Graft Survival; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism*; D013995:Time; D017211:Treatment Failure