Dataset Information

Fate of culture-expanded mesenchymal stem cells in the microvasculature: in vivo observations of cell kinetics.

ABSTRACT: Vascular delivery of mesenchymal stem cells (MSCs) following myocardial infarction is under clinical investigation. Little is known about the microvascular fate of MSCs. We used intravital microscopy of rat cremaster muscle microcirculation to track intraarterially delivered MSCs. Rat MSCs (average diameter, 23 microm) were bolused into the ipsilateral common iliac artery. Interrogation of an arteriole-venule pair revealed that 92+/-7% (n=6) of MSCs arrest and interrupt flow during first pass at the precapillary level, resulting in decreased flow in the feeding arteriole (velocity decreased from 6.3+/-1.0 to 4.6+/-1.3 mm/sec; P<0.001). MSC deformability evaluated using filtration through polycarbonate membranes revealed that the cortical tension of MSCs (0.49+/-0.07 dyne/cm, n=9) was not different from that of circulating mononuclear cells (0.50+/-0.05 dyne/cm, n=7). When intravital microscopy was performed 3 days following injection, the number of MSCs in the cremaster further decreased to 14% of the initial number, because of cell death in situ. In vivo labeling of the basement membrane revealed that at 1 day, the surviving cells were spread out on the luminal side of the microvessel, whereas at 3 days, they integrated in the microvascular wall. Despite their deformability, intraarterially delivered MSCs entrap at the precapillary level because of their large size, with a small proportion of surviving MSCs integrating in a perivascular niche.

SUBMITTER: Toma C

PROVIDER: S-EPMC3700384 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Fate of culture-expanded mesenchymal stem cells in the microvasculature: in vivo observations of cell kinetics.

Toma Catalin C Wagner William R WR Bowry Shivani S Schwartz Abigail A Villanueva Flordeliza F

Circulation research 20081218 3

Vascular delivery of mesenchymal stem cells (MSCs) following myocardial infarction is under clinical investigation. Little is known about the microvascular fate of MSCs. We used intravital microscopy of rat cremaster muscle microcirculation to track intraarterially delivered MSCs. Rat MSCs (average diameter, 23 microm) were bolused into the ipsilateral common iliac artery. Interrogation of an arteriole-venule pair revealed that 92+/-7% (n=6) of MSCs arrest and interrupt flow during first pass at ...[more]

PMID: 19096027

Similar Datasets

Project description:Human culture-expanded mesenchymal stromal cells (MSC) are being considered for multiple therapeutic applications because of their regenerative and anti-inflammatory properties. Although a large number of MSC can be propagated from a small initial sample, several lines of evidence indicate that MSC lose their immunosuppressive and regenerative potency aftaer multiple passages. In this report, we use the FACSCAP Lyoplate proteomic analysis system to detect changes in cell surface protein expression of CD45- /CD31- /CD34- /CD73+ /CD105+ stromal cells in unpassaged bone marrow (BM) and through 10 serial culture passages. We provide for the first time a detailed characterization of native unpassaged BM MSC (0.08% of BM mononuclear cells) as well as the changes that occur during the initial expansion. Adipogenic and osteogenic differentiative potential was determined though the serial passages and correlated with immunophenotypic changes and senescence. Among the most prominent were striking decreases in Fas ligand, CD98, CD205, and CD106, accompanied by a gain in the expression of CD49c, CD63, CD98, and class 1 and class 2 major histocompatibility complex (MHC) molecules. Other molecules that are down-modulated with later passage include CD24, CD54, CD59, CD243/P-glycoprotein, and CD273/PD-L2. Early senescence, as defined by the loss of replicative capacity occurring with the loss of differentiative capacity, increase in CDKN2A p16, and increased time to confluence, was accompanied by loss of the motility-associated metalloproteinase CD10 and the proliferation-associated transferrin receptor CD71. Among the strongest statistical associations were loss of MAC-inhibitory protein/CD59, loss of ICAM-1/CD54, and increase in CDKN2A as a function of increasing passage, as well as increased CD10 expression with adipogenic and osteogenic capacities. The data provide a clear set of markers that can be used to assess MSC quality. We suggest that clinically relevant numbers of highly functional low passage MSC can be manufactured starting with large quantities of BM, which are readily available from cadaveric organ donors.

Dataset Information

Fate of culture-expanded mesenchymal stem cells in the microvasculature: in vivo observations of cell kinetics.

Publications

Fate of culture-expanded mesenchymal stem cells in the microvasculature: in vivo observations of cell kinetics.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets