Angiogenic effects despite limited cell survival of bone marrow-derived mesenchymal stem cells under ischemia
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Angiogenic effects despite limited cell survival of bone marrow-derived mesenchymal stem cells under ischemia. / Hoffmann, J; Glassford, A J; Doyle, T C; Robbins, R C; Schrepfer, S; Pelletier, M P.
In: THORAC CARDIOV SURG, Vol. 58, No. 3, 04.2010, p. 136-142.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Angiogenic effects despite limited cell survival of bone marrow-derived mesenchymal stem cells under ischemia
AU - Hoffmann, J
AU - Glassford, A J
AU - Doyle, T C
AU - Robbins, R C
AU - Schrepfer, S
AU - Pelletier, M P
N1 - Georg Thieme Verlag KG Stuttgart New York.
PY - 2010/4
Y1 - 2010/4
N2 - Bone marrow-derived mesenchymal stem cells (MSCs) are multipotent and secrete angiogenic factors, which could help patients with occlusive arterial diseases. We hypothesize that MSCs, in comparison to fibroblasts, survive better under hypoxic conditions in vitro and in vivo. MSCs and fibroblasts from L2G mice expressing firefly luciferase and GFP were cultured in normoxic and hypoxic conditions for 24 hours. In vitro cell viability was tested by detecting apoptosis and necrosis. MSCs released higher amounts of VEGF (281.1 +/- 62.6 pg/ml) under hypoxic conditions compared to normoxia (154.9 +/- 52.3 pg/ml, p = NS), but were less tolerant to hypoxia (45 +/- 7.9%) than fibroblasts (28.1 +/- 3.6%, p = NS). A hindlimb ischemia model was created by ligating the femoral artery of 18 FVB mice. After one week, 1 x 106 cells (MSCs, fibroblasts or saline) were injected into the limb muscles of each animal (n = 6 per group). Bioluminescence measurement to assess the viability of luciferase positive cells showed significant proliferation of MSCs on day four compared to fibroblasts (p = 0.001). Three weeks after cell delivery, the capillary to muscle fiber ratio of ischemic areas was analyzed. In the MSC group, vessel density was significantly higher than in the fibroblast or control group (0.5 +/- 0.08 and 0.3 +/- 0.03). Under hypoxia, MSCs produced more VEGF compared to normal conditions and MSC transplantation into murine ischemic limbs led to an increase in vessel density, although MSC survival was limited. This study suggests that MSC transplantation may be an effective and clinically relevant tool in the therapy of occlusive arterial diseases.
AB - Bone marrow-derived mesenchymal stem cells (MSCs) are multipotent and secrete angiogenic factors, which could help patients with occlusive arterial diseases. We hypothesize that MSCs, in comparison to fibroblasts, survive better under hypoxic conditions in vitro and in vivo. MSCs and fibroblasts from L2G mice expressing firefly luciferase and GFP were cultured in normoxic and hypoxic conditions for 24 hours. In vitro cell viability was tested by detecting apoptosis and necrosis. MSCs released higher amounts of VEGF (281.1 +/- 62.6 pg/ml) under hypoxic conditions compared to normoxia (154.9 +/- 52.3 pg/ml, p = NS), but were less tolerant to hypoxia (45 +/- 7.9%) than fibroblasts (28.1 +/- 3.6%, p = NS). A hindlimb ischemia model was created by ligating the femoral artery of 18 FVB mice. After one week, 1 x 106 cells (MSCs, fibroblasts or saline) were injected into the limb muscles of each animal (n = 6 per group). Bioluminescence measurement to assess the viability of luciferase positive cells showed significant proliferation of MSCs on day four compared to fibroblasts (p = 0.001). Three weeks after cell delivery, the capillary to muscle fiber ratio of ischemic areas was analyzed. In the MSC group, vessel density was significantly higher than in the fibroblast or control group (0.5 +/- 0.08 and 0.3 +/- 0.03). Under hypoxia, MSCs produced more VEGF compared to normal conditions and MSC transplantation into murine ischemic limbs led to an increase in vessel density, although MSC survival was limited. This study suggests that MSC transplantation may be an effective and clinically relevant tool in the therapy of occlusive arterial diseases.
KW - Angiogenic Proteins/metabolism
KW - Animals
KW - Apoptosis
KW - Capillaries/physiopathology
KW - Cell Hypoxia
KW - Cell Proliferation
KW - Cell Survival
KW - Cells, Cultured
KW - Disease Models, Animal
KW - Female
KW - Fibroblasts/metabolism
KW - Green Fluorescent Proteins/biosynthesis
KW - Hindlimb
KW - Ischemia/pathology
KW - Luciferases, Firefly/biosynthesis
KW - Male
KW - Mesenchymal Stem Cell Transplantation
KW - Mesenchymal Stem Cells/metabolism
KW - Mice
KW - Mice, Transgenic
KW - Muscle, Skeletal/blood supply
KW - Necrosis
KW - Neovascularization, Physiologic
KW - Time Factors
U2 - 10.1055/s-0029-1240758
DO - 10.1055/s-0029-1240758
M3 - SCORING: Journal article
C2 - 20379963
VL - 58
SP - 136
EP - 142
JO - THORAC CARDIOV SURG
JF - THORAC CARDIOV SURG
SN - 0171-6425
IS - 3
ER -
