Adipose tissue-derived stem cells inhibit neointimal formation in a paracrine fashion in rat femoral artery

2010 ◽  
Vol 298 (2) ◽  
pp. H415-H423 ◽  
Author(s):  
Masao Takahashi ◽  
Etsu Suzuki ◽  
Shigeyoshi Oba ◽  
Hiroaki Nishimatsu ◽  
Kenjiro Kimura ◽  
...  
Keyword(s):  
Stem Cells ◽  
Adipose Tissue ◽  
Femoral Artery ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial ◽  
Neointimal Formation ◽  
Paracrine Factors ◽  
Endothelial Layer ◽  
Endothelial Repair

Subcutaneous adipose tissue contains a lot of stem cells [adipose-derived stem cells (ASCs)] that can differentiate into a variety of cell lineages. In this study, we isolated ASCs from Wistar rats and examined whether ASCs would efficiently differentiate into vascular endothelial cells (ECs) in vitro. We also administered ASCs in a wire injury model of rat femoral artery and examined their effects. ASCs expressed CD29 and CD90, but not CD34, suggesting that ASCs resemble bone marrow-derived mesenchymal stem cells. When induced to differentiate into ECs with endothelial growth medium (EGM), ASCs expressed Flt-1, but not Flk-1 or mature EC markers such as CD31 and vascular endothelial cadherin. ASCs produced angiopoietin-1 when they were cultured in EGM. ASCs stimulated the migration of EC, as assessed by chemotaxis assay. When ASCs that were cultured in EGM were injected in the femoral artery, the ASCs potently and significantly inhibited neointimal formation without being integrated in the endothelial layer. EGM-treated ASCs significantly suppressed neointimal formation even when they were administered from the adventitial side. ASC administration significantly promoted endothelial repair. These results suggested that although ASCs appear to have little capacity to differentiate into mature ECs, ASCs have the potential to secrete paracrine factors that stimulate endothelial repair. Our results also suggested that ASCs inhibited neointimal formation via their paracrine effect of stimulation of EC migration in situ rather than the direct integration into the endothelial layer.

scholarly journals Comparative analysis of mouse bone marrow and adipose tissue mesenchymal stem cells for critical limb ischemia cell therapy

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pegah Nammian ◽  
Seyedeh-Leili Asadi-Yousefabad ◽  
Sajad Daneshi ◽  
Mohammad Hasan Sheikhha ◽  
Seyed Mohammad Bagher Tabei ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Cell Therapy ◽  
Femoral Artery ◽  
Critical Limb Ischemia ◽  
Limb Ischemia

Abstract Introduction Critical limb ischemia (CLI) is the most advanced form of peripheral arterial disease (PAD) characterized by ischemic rest pain and non-healing ulcers. Currently, the standard therapy for CLI is the surgical reconstruction and endovascular therapy or limb amputation for patients with no treatment options. Neovasculogenesis induced by mesenchymal stem cells (MSCs) therapy is a promising approach to improve CLI. Owing to their angiogenic and immunomodulatory potential, MSCs are perfect candidates for the treatment of CLI. The purpose of this study was to determine and compare the in vitro and in vivo effects of allogeneic bone marrow mesenchymal stem cells (BM-MSCs) and adipose tissue mesenchymal stem cells (AT-MSCs) on CLI treatment. Methods For the first step, BM-MSCs and AT-MSCs were isolated and characterized for the characteristic MSC phenotypes. Then, femoral artery ligation and total excision of the femoral artery were performed on C57BL/6 mice to create a CLI model. The cells were evaluated for their in vitro and in vivo biological characteristics for CLI cell therapy. In order to determine these characteristics, the following tests were performed: morphology, flow cytometry, differentiation to osteocyte and adipocyte, wound healing assay, and behavioral tests including Tarlov, Ischemia, Modified ischemia, Function and the grade of limb necrosis scores, donor cell survival assay, and histological analysis. Results Our cellular and functional tests indicated that during 28 days after cell transplantation, BM-MSCs had a great effect on endothelial cell migration, muscle restructure, functional improvements, and neovascularization in ischemic tissues compared with AT-MSCs and control groups. Conclusions Allogeneic BM-MSC transplantation resulted in a more effective recovery from critical limb ischemia compared to AT-MSCs transplantation. In fact, BM-MSC transplantation could be considered as a promising therapy for diseases with insufficient angiogenesis including hindlimb ischemia.

Efficiently differentiating vascular endothelial cells from adipose tissue-derived mesenchymal stem cells in serum-free culture

2010 ◽  
Vol 400 (4) ◽  
pp. 461-465 ◽  
Author(s):  
Masamitsu Konno ◽  
Tatsuo S. Hamazaki ◽  
Satsuki Fukuda ◽  
Makoto Tokuhara ◽  
Hideho Uchiyama ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial ◽  
Serum Free

scholarly journals VEGFR1 primes a unique cohort of dental pulp stem cells for vasculogenic differentiation

2021 ◽  
Vol 41 ◽  
pp. 332-344
Author(s):  
MT Bergamo ◽  
◽  
Z Zhang ◽  
TM Oliveira ◽  
JE Nör
Keyword(s):  
Stem Cells ◽  
Dental Pulp ◽  
Vascular Endothelial Cells ◽  
Dental Pulp Stem Cells ◽  
Deciduous Teeth ◽  
Microvascular Endothelial Cell ◽  
Vascular Endothelial ◽  
Pulp Tissue ◽  
Immunodeficient Mice

Dental pulp stem cells (DPSCs) constitute a unique group of cells endowed with multipotency, self-renewal, and capacity to regenerate the dental pulp tissue. While much has been learned about these cells in recent years, it is still unclear if each DPSC is multipotent or if unique sub-populations of DPSCs are “primed” to undergo specific differentiation paths. The purpose of the present study was to define whether a sub-population of DPSCs was uniquely primed to undergo vasculogenic differentiation. Permanent-tooth DPSCs or stem cells from human exfoliated deciduous teeth (SHED) were flow-sorted for vascular endothelial growth factor receptor 1 (VEGFR1) and exposed to vasculogenic differentiation medium, i.e., Microvascular-Endothelial-Cell-Growth-Medium-2-BulletKit™ supplemented with 50 ng/mL rhVEGF165 in the presence of 0 or 25 μg/mL anti-human VEGF antibody (bevacizumab; Genentech). In addition, sorted SHED (i.e., VEGFR1high or VEGFR1low) were seeded in biodegradable scaffolds and transplanted into the subcutaneous space of immunodeficient mice. Despite proliferating at a similar rate, VEGFR1high generated more in vitro sprouts than VEGFR1low cells (p < 0.05). Blockade of VEGF signaling with bevacizumab inhibited VEGFR1high-derived sprouts, demonstrating specificity of responses. Similarly, VEGFR1high SHED generated more blood vessels when transplanted into murine hosts than VEGFR1low cells (p < 0.05). Collectively, these data demonstrated that DPSCs contain a unique sub-population of cells defined by high VEGFR1 expression that are primed to differentiate into vascular endothelial cells. These data raise the possibility of purifying stem cells with high vasculogenic potential for regeneration of vascularized tissues or for vascular engineering in the treatment of ischemic conditions.

Abstract 1196: Vascular Endothelial Cells specific Endothelin-1 mediates Early Inflammation in Murine Model of Neointimal Formation

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Dyah Wulan Anggrahini ◽  
Suko Adiarto ◽  
Naoko Iwasa ◽  
Kazuhiko Nakayama ◽  
Bambang Widyantoro ◽  
...  
Keyword(s):  
Carotid Artery ◽  
Vascular Injury ◽  
Vascular Endothelial Cells ◽  
Vascular Inflammation ◽  
Mrna Level ◽  
Vascular Endothelial ◽  
Neointimal Formation ◽  
Endothelin 1

Complex mechanism of the chronic inflammatory process in vascular injury and atherosclerosis involves various types of cells and cytokines. Previous in vitro studies suggest that Endothelin-1 (ET-1) is produced by those cells, induces expression of several adhesion molecules and mediates the leukocyte-endothelial interaction. In the present study, we sought to determine whether local endothelial ET-1 plays a direct effect on early inflammation and neointimal formation as a response to vascular injury in vivo . Using Cre-loxP system and Tie-2 Cre promoter, Vascular Endothelial ET-1 Knockout (VEETKO) mice was generated. The mice showed 60% reduction of ET-1 mRNA level at major organs and undetected serum ET-1 level. To induce vascular inflammation, complete ligation of the left common carotid artery was performed in 12-weeks-old male VEETKO (n=35) and Wild Type (WT) littermates (n=34). Inhibition of vascular endothelial ET-1 prevented the 4-fold increase in ET-1 mRNA level of carotid artery after ligation, in contrast to that of WT mice. This prevention resulted in lower vascular inflammation revealed by lower mRNA and protein level of PECAM-1, ICAM-1, and MCP-1 in VEETKO mice. The lack of ET-1 in endothelium further inhibited the adhesion of inflammatory cells at early days after ligation as compared to that adhered in endothelium of WT mice (cell numbers, 20.7±4.9 vs. 54.6±3.9 respectively, p<0.05, VEEETKO n=8/WT n=10). Observation at 4 weeks after ligation noted lower neointimal formation in VEETKO mice (n=11) as compared to WT littermates (n=12) (neointimal/medial ratio, 0.2±0.03 vs. 0.8±0.25 respectively, p<0.05). Changes in carotid flow gave no hemodynamical effect as sistolic blood pressure maintained significantly lower in VEETKO mice as compared to WT mice (105.7±1.4 vs. 115.9±1.6 mmHg before ligation, p<0.05 and 105.7±2.4 vs.119.08±1.08 mmHg after ligation, p<0.05 n=20 each). In conclusion, these data demonstrated that lack of vascular endothelial ET-1 reduced inflammatory response of the vascular wall followed by inhibition of neointimal formation confirming the role of local endothelial ET-1 in mediating inflammation in vascular injury, in addition to its potent vasoconstrictor and proliferating effect.

scholarly journals Efficient differentiation of vascular endothelial cells from dermal-derived mesenchymal stem cells induced by endothelial cell lines conditioned medium

2018 ◽  
Author(s):  
Ling Zhou ◽  
Xuping Niu ◽  
Jiannan Liang ◽  
Junqin Li ◽  
Jiao Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Flow Cytometry ◽  
Endothelial Cells ◽  
Mesenchymal Stem Cells ◽  
Vascular Endothelial Cells ◽  
The Other ◽  
Immunofluorescent Staining ◽  
Enzyme Linked Immunosorbent Assay ◽  
Vascular Endothelial

AbstractObjectiveTo directionally-differentiate dermis-derived mesenchymal stem cells (DMSCs) into vascular endothelial cells (VECs) in vitro, providing an experimental basis for studies on the pathogenesis and treatment of vascular diseases.MethodsAfter separation by adherent culture, VEC line supernatant, vascular endothelial growth factor (VEGF), bone morphogenetic protein-4 and hypoxia were used for the differentiation of VECs from DMSCs. The cell type was authenticated by flow cytometry, matrigel angiogenesis assay in vitro, and immunofluorescent staining during differentiation. The VEGF concentration was investigated by enzyme-linked immunosorbent assay.ResultsAfter 28 days of differentiation, the cell surface marker CD31 was significantly positive (80%-90%) by flow cytometry in the VEC line-conditioned culture, which was significantly higher than in the other groups. Differentiated DMSCs had the ability to ingest Dil-ac-LDL and vascularize in the conditioned culture, but not in the other groups. In the VEC line supernatant, the concentration of VEGF was very low. The VEGF concentration changed along with the differentiation into VECs in the medium of the conditioned culture group.ConclusionVEC line supernatant can induce the differentiation of DMSCs into VECs, possibly through the pathway except VEGF.

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