Mesenchymal stem cells effectively reduce surgically induced stenosis in rat carotids

Abstract

Restenosis following vascular injury remains a pressing clinical problem. Mesenchymal stem cells (MSCs) promise as a main actor of cell-based therapeutic strategies. The possible therapeutic role of MSCs in vascular stenosis in vivo has been poorly investigated so far. We tested the effectiveness of allogenic bone marrow-derived MSCs in reduction of stenosis in a model of rat carotid arteriotomy. MSCs were expanded in vitro retaining their proliferative and differentiation potentiality. MSCs were able to differentiate into adipocyte and osteocyte mesenchymal lineage cells, retained specific antigens CD73, CD90, and CD105, expressed smooth muscle alpha-actin, were mainly in proliferative phase of cell cycle and showed limited senescence. WKY rats were submitted to carotid arteriotomy and to venous administration with 5 x 10(6) MSCs. MSCs in vivo homed in injured carotids since 3 days after arteriotomy but not in contralateral uninjured carotids. Lumen area in MSC-treated carotids was 36% greater than in control arteries (P = 0.016) and inward remodeling was limited in MSC-treated carotids (P = 0.030) 30 days after arteriotomy. MSC treatment affected the expression level of inflammation-related genes, inducing a decrease of IL-1beta and Mcp-1 and an increase of TGF-beta in injured carotids at 3 and 7 days after arteriotomy (P < 0.05). Taken together, these results indicate that allogenic MSC administration limits stenosis in injured rat carotids and plays a local immunomodulatory action.

A Method for Performing Islet Transplantation Using Tissue-Engineered Sheets of Islets and Mesenchymal Stem Cells

“…These findings indicated that the characteristic immunophenotype of rat bone marrow-derived MSCs was exhibited in the isolated cells. [25][26][27] MSCs have the ability to differentiate into osteogenic and adipogenic lineages. 25,26 The cells described herein are able to differentiate into osteocytes and adipocytes (Fig.…”

Mechanistic Insights into Arterial Repair with Mesenchymal Stromal Cells

“…These ultimately lead to excessive neointima formation and re-narrowing of the arterial lumen. Although its frequency has declined in recent years, the residual risk of restenosis after percutaneous and surgical revascularization has prompted ongoing evaluation of experimental strategies to prevent or treat its progression, including the administration of different progenitor cell types to facilitate normal arterial healing and avert aberrant, deleterious repair [3][4][5][6][7].…”

“…To this end, Forte et al have previously reported that systemic infusion of allogeneic BM MSCs resulted in attenuation of inward remodeling and luminal narrowing thirty days into a rodent model of carotid artery crush and arteriotomy [3]. This surgical model has the important distinction from wire or balloon injury in that it creates a greater degree of arterial wall trauma by disrupting both the internal and external elastic lamina.…”

Vascular Endoluminal Delivery of Mesenchymal Stem Cells Using Acoustic Radiation Force

“…Clearly, this method can be used for endovascular seeding of other cell types, such as EPCs. The rationale behind using MSCs in our study stems from robust data indicating that seeding of a sufficient number of MSCs on vascular grafts, 5,17 acellular bioprosthetic valves, 18 or injured vascular segments 6,7,19 leads to improved endothelialization and decreased neointimal formation, not necessarily by direct MSC endothelial differentiation, but likely via paracrine mechanisms. 19 To this point, MSCs secrete vascular endothelial growth factor, insulin-like growth factor, and hematopoietic growth factor, 20 stimulate endogenous angiogenesis, and have a positive effect on the endothelium.…”

“…3,4 Another potentially attractive therapeutic cell is the bone marrow-derived mesenchymal stem cell (MSC), which has been shown to facilitate re-endothelialization of prosthetic vascular grafts 5 and to reduce neointimal formation after vascular injury. 6,7 One limitation to the development of cell therapy specifically for vascular healing is the lack of a delivery method that is efficacious in moving cells to, and arresting them at, the vascular wall under the conditions of high shear stress present in arteries. To this end, we hypothesized that acoustic radiation force can be employed to selectively displace therapeutic cells coated with microbubbles to a specific vascular segment (Fig.…”