Smooth-muscle progenitor cells of bone marrow origin contribute to the development of neointimal thickenings in rat aortic allografts and injured rat carotid arteries1

Abstract

This study indicates that circulating progenitors of bone marrow origin give rise to cells with smooth muscle-like properties during formation of neointimal thickenings in the arterial wall after allotransplantation and after balloon injury. A segment of abdominal aorta was transplanted from female F344 to male LEW rats, and the grafts were analyzed for male cells by using the gene as a marker. Immunostaining demonstrated that CD45-positive leukocytes made up 35-45% of the neointimal cells during the 8-week period examined. Concurrently, up to 70% of the neointimal cells were of host origin, as shown by real-time polymerase chain reaction for the gene (Y chromosome). This suggests that the neointima contained host cells also of noninflammatory character. Accordingly, many cells positive for smooth-muscle alpha-actin were detected in this layer. To explore the possible bone marrow origin of allograft cells, female LEW rats were irradiated and substituted with bone marrow from male LEW rats. Subsequently, the animals received an aortic transplant from female F344 rats or were exposed to a balloon injury of the carotid artery. Immunostaining and real-time polymerase chain reaction confirmed the above findings, but the fractions of leukocytes and -positive cells were lower in the carotids than in the allografts. Combined primed in situ labeling and immunostaining verified that not only inflammatory but also smooth muscle-like cells of male origin appeared in the vessel wall in both situations. These observations suggest that the smooth-muscle cells that participate in the development of neointimal lesions during vascular disease may, in part, originate from circulating progenitors.

c-Kit signaling determines neointimal hyperplasia in arteriovenous fistulae

“…The existence of stem cells in the fistula wall was recently suggested by Caplice et al (8), who described this type of cells as components of adventitial microvessels in the rat A-V fistula. A number of studies have proposed bone marrow-derived progenitor cells as the source of neointimal cells in stenotic blood vessels after arterial injury (38,44,46), but their contribution seems less pronounced in the case of venous hyperplasia, as clearly demonstrated in three independent studies (9,21,43). The present work highlights the critical role played by this pathway in A-V fistula remodeling.…”

Clonogenic multipotent stem cells in human adipose tissue differentiate into functional smooth muscle cells

“…In vitro, marrow stromal cells have been shown to differentiate into bone, fat, cartilage, neuron, or muscle when treated with specialized induction media. Recent studies have indicated that smooth muscle-like cells also can be derived from bone marrow cells both in vitro (17,18) or in vivo (3,5). However, bone marrow is not the only site of adult stem cells capable of multiple differentiation.…”

“…Several groups have suggested the use of bone marrow-derived cells (3)(4)(5) and embryonic stem cells to repair smooth muscle tissues (6,7) because of their stem cell-like properties. Adipose tissue represents a potential alternative reservoir of cells with stem cell properties such as self-renewal and pluripotency.…”

Crucial Role of Stromal Cell–Derived Factor-1α in Neointima Formation After Vascular Injury in Apolipoprotein E–Deficient Mice

“…Application of a blocking SDF-1␣ mAb reduces neointimal area and neointimal SMC content, which indicates an important role during the progression of accelerated atherosclerosis. Because SDF-1␣ is important in the homeostasis of bone marrow homing and mobilization of progenitor cells, 7,19 and neointimal SMCs originate from a bone marrow source of progenitors, [13][14][15] we studied the effect of SDF-1␣ on progenitor cell mobilization and recruitment after carotid injury. We found that the expansion of PBPCs in the circulation and the accumulation of injected PBPCs in established neointimal lesions were mediated by SDF-1␣.…”

“…Furthermore, neutralization of SDF-1␣ after carotid injury in apolipoprotein E-deficient (apoE Ϫ/Ϫ ) mice by application of a blocking antibody was evaluated for its effect on neointimal lesions. Bone marrowderived cells have been shown to contribute to neointimal SMC content, [13][14][15] and circulating SMC progenitors have been demonstrated in humans. 16 We therefore determined whether SDF-1␣ is involved in the mobilization of progenitor cells into the peripheral blood and whether these cells can be recruited to neointimal lesions and adopt an SMC phenotype.…”