8 research outputs found
Transplantation of mesenchymal stem cells exerts a greater long-term effect than bone marrow mononuclear cells in a chronic myocardial infarction model in rat
The aim of this study is to assess the long-term effect of mesenchymal stem cells (MSC) transplantation in
a rat model of chronic myocardial infarction (MI) in comparison with the effect of bone marrow mononuclear
cells (BM-MNC) transplant. Five weeks after induction of MI, rats were allocated to receive intramyocardial
injection of 106 GFP-expressing cells (BM-MNC or MSC) or medium as control. Heart function
(echocardiography and 18F-FDG-microPET) and histological studies were performed 3 months after transplantation
and cell fate was analyzed along the experiment (1 and 2 weeks and 1 and 3 months). The main
findings of this study were that both BM-derived populations, BM-MNC and MSC, induced a long-lasting
(3 months) improvement in LVEF (BM-MNC: 26.61 ± 2.01% to 46.61 ± 3.7%, p < 0.05; MSC: 27.5 ±
1.28% to 38.8 ± 3.2%, p < 0.05) but remarkably, only MSC improved tissue metabolism quantified by 18FFDG
uptake (71.15 ± 1.27 to 76.31 ± 1.11, p < 0.01), which was thereby associated with a smaller infarct size
and scar collagen content and also with a higher revascularization degree. Altogether, results show that MSC
provides a long-term superior benefit than whole BM-MNC transplantation in a rat model of chronic MI
Histological and ultrastructural comparison of cauterization and thrombosis stroke models in immune-deficient mice
Background: Stroke models are essential tools in experimental stroke. Although several models of stroke have
been developed in a variety of animals, with the development of transgenic mice there is the need to develop a
reliable and reproducible stroke model in mice, which mimics as close as possible human stroke.
Methods: BALB/Ca-RAG2-/-gc-/- mice were subjected to cauterization or thrombosis stroke model and sacrificed at
different time points (48hr, 1wk, 2wk and 4wk) after stroke. Mice received BrdU to estimate activation of cell
proliferation in the SVZ. Brains were processed for immunohistochemical and EM.
Results: In both stroke models, after inflammation the same glial scar formation process and damage evolution
takes place. After stroke, necrotic tissue is progressively removed, and healthy tissue is preserved from injury
through the glial scar formation. Cauterization stroke model produced unspecific damage, was less efficient and
the infarct was less homogeneous compared to thrombosis infarct. Finally, thrombosis stroke model produces
activation of SVZ proliferation.
Conclusions: Our results provide an exhaustive analysis of the histopathological changes (inflammation, necrosis,
tissue remodeling, scarring...) that occur after stroke in the ischemic boundary zone, which are of key importance
for the final stroke outcome. This analysis would allow evaluating how different therapies would affect wound and
regeneration. Moreover, this stroke model in RAG 2-/- gC -/- allows cell transplant from different species, even
human, to be analyzed
Therapeutic effects of hMAPC and hMSC transplantation after stroke in mice
Stroke represents an attractive target for stem cell therapy. Although different types of cells have been employed in animal models, a direct comparison between cell sources has not been performed. The aim of our study was to assess the effect of human multipotent adult progenitor cells (hMAPCs) and human mesenchymal stem cells (hMSCs) on endogenous neurogenesis, angiogenesis and inflammation following stroke. BALB/Ca-RAG 2(-/-) γC(-/-) mice subjected to FeCl(3) thrombosis mediated stroke were intracranially injected with 2 × 10(5) hMAPCs or hMSCs 2 days after stroke and followed for up to 28 days. We could not detect long-term engraftment of either cell population. However, in comparison with PBS-treated animals, hMSC and hMAPC grafted animals demonstrated significantly decreased loss of brain tissue. This was associated with increased angiogenesis, diminished inflammation and a glial-scar inhibitory effect. Moreover, enhanced proliferation of cells in the subventricular zone (SVZ) and survival of newly generated neuroblasts was observed. Interestingly, these neuroprotective effects were more pronounced in the group of animals treated with hMAPCs in comparison with hMSCs. Our results establish cell therapy with hMAPCs and hMSCs as a promising strategy for the treatment of strok
Therapeutic effects of hMAPC and hMSC transplantation after stroke in mice
Stroke represents an attractive target for stem cell therapy. Although different types of cells have been employed in animal models, a direct comparison between cell sources has not been performed. The aim of our study was to assess the effect of human multipotent adult progenitor cells (hMAPCs) and human mesenchymal stem cells (hMSCs) on endogenous neurogenesis, angiogenesis and inflammation following stroke. BALB/Ca-RAG 2(-/-) γC(-/-) mice subjected to FeCl(3) thrombosis mediated stroke were intracranially injected with 2 × 10(5) hMAPCs or hMSCs 2 days after stroke and followed for up to 28 days. We could not detect long-term engraftment of either cell population. However, in comparison with PBS-treated animals, hMSC and hMAPC grafted animals demonstrated significantly decreased loss of brain tissue. This was associated with increased angiogenesis, diminished inflammation and a glial-scar inhibitory effect. Moreover, enhanced proliferation of cells in the subventricular zone (SVZ) and survival of newly generated neuroblasts was observed. Interestingly, these neuroprotective effects were more pronounced in the group of animals treated with hMAPCs in comparison with hMSCs. Our results establish cell therapy with hMAPCs and hMSCs as a promising strategy for the treatment of strok
In vitro and in vivo arterial differentiation of human multipotent adult progenitor cells
Many stem cell types have been shown to
differentiate into endothelial cells (ECs);
however, their specification to arterial or
venous endothelium remains unexplored.
We tested whether a specific arterial or
venous EC fate could be induced in human
multipotent adult progenitor cells
(hMAPCs) and AC133 cells (hAC133 ).
In vitro, in the presence of VEGF165,
hAC133 cells only adopted a venous and
microvascular EC phenotype, while
hMAPCs differentiated into both arterial
and venous ECs, possibly because
hMAPCs expressed significantly more
sonic hedgehog (Shh) and its receptors
as well as Notch 1 and 3 receptors and
some of their ligands. Accordingly, blocking
either of those pathways attenuated
in vitro arterial EC differentiation from
hMAPCs. Complementarily, stimulating
these pathways by addition of Delta-like 4
(Dll-4), a Notch ligand, and Shh to VEGF165
further boosted arterial differentiation in
hMAPCs both in vitro and in an in vivo
Matrigel model. These results represent
the first demonstration of adult stem cells
with the potential to be differentiated into
different types of ECs in vitro and in vivo
and provide a useful human model to
study arteriovenous specification
Can bone marrow-derived multipotent adult progenitor cells regenerate infarcted myocardium?
Thymidine Analogs Are Transferred from Prelabeled Donor to Host Cells in the Central Nervous System After Transplantation: A Word of Caution
Thymidine analogs, including bromodeoxyuridine, chlorodeoxyuridine,
iododeoxyuridine, and tritiated thymidine, label
dividing cells by incorporating into DNA during S phase of cell
division and are widely employed to identify cells transplanted
into the central nervous system. However, the potential for
transfer of thymidine analogs from grafted cells to dividing
host cells has not been thoroughly tested. We here demonstrate
that graft-derived thymidine analogs can become incorporated
into host neural precursors and glia. Large numbers of labeled
neurons and glia were found 3–12 weeks after transplantation
of thymidine analog-labeled live stem cells, suggesting differentiation
of grafted cells. Remarkably, however, similar results
were obtained after transplantation of dead cells or labeled
fibroblasts. Our findings reveal for the first time that thymidine
analog labeling may not be a reliable means of identifying
transplanted cells, particularly in highly proliferative environments
such as the developing, neurogenic, or injured brain
Thymidine Analogs Are Transferred from Prelabeled Donor to Host Cells in the Central Nervous System After Transplantation: A Word of Caution
Thymidine analogs, including bromodeoxyuridine, chlorodeoxyuridine,
iododeoxyuridine, and tritiated thymidine, label
dividing cells by incorporating into DNA during S phase of cell
division and are widely employed to identify cells transplanted
into the central nervous system. However, the potential for
transfer of thymidine analogs from grafted cells to dividing
host cells has not been thoroughly tested. We here demonstrate
that graft-derived thymidine analogs can become incorporated
into host neural precursors and glia. Large numbers of labeled
neurons and glia were found 3–12 weeks after transplantation
of thymidine analog-labeled live stem cells, suggesting differentiation
of grafted cells. Remarkably, however, similar results
were obtained after transplantation of dead cells or labeled
fibroblasts. Our findings reveal for the first time that thymidine
analog labeling may not be a reliable means of identifying
transplanted cells, particularly in highly proliferative environments
such as the developing, neurogenic, or injured brain