Vascular endothelial growth factor-transfected adipose-derived stromal cells enhance bone regeneration and neovascularization from bone marrow stromal cells

2017 ◽  
Vol 11 (12) ◽  
pp. 3337-3348 ◽  
Author(s):  
Mi-Lan Kang ◽  
Ji-Eun Kim ◽  
Gun-Il Im
2007 ◽  
Vol 27 (10) ◽  
pp. 1684-1691 ◽  
Author(s):  
Alex Zacharek ◽  
Jieli Chen ◽  
Ang Li ◽  
Xu Cui ◽  
Yi Li ◽  
...  

Bone marrow stromal cells (MSCs) increase vascular endothelial growth factor (VEGF) expression and promote angiogenesis after stroke. Angiopoietin-1 (Ang1) and its receptor Tie2 mediate vascular integrity and angiogenesis as does VEGF and its receptors. In this study, we tested whether MSC treatment of stroke increases Ang1/Tie2 expression, and whether Ang1/Tie2 with VEGF / vascular endothelial growth factor receptor 2 (VEGFR2) (Flk1), in combination, induced by MSCs enhances angiogenesis and vascular integrity. Male Wistar rats were subjected to middle cerebral artery occlusion (MCAo) and treated with or without MSCs. Marrow stromal cell treatment significantly decreased blood—brain barrier (BBB) leakage and increased Ang1, Tie2, and occludin (a tight junction protein) expression in the ischemic border compared with MCAo control. To further test the mechanisms of MSC-induced angiogenesis and vascular stabilization, cocultures of MSCs with mouse brain endothelial cells (MBECs) or astrocytes were performed. Supernatant derived from MSCs cocultured with MBECs significantly increased MBEC expression of Ang1/Tie2 and Flk1 compared with MBEC alone. Marrow stromal cells cocultured with astrocytes also significantly increased astrocyte VEGF and Ang1/Tie2 expression compared with astrocyte culture alone. Conditioned media from MSCs alone, and media from cocultures of MSCs with astrocytes or MBECs, all significantly increased capillary tube-like formation of MBEC compared with control Dulbecco's modified Eagle's medium media. Inhibition of Flk1 and/or Ang1 significantly decreased MSC-induced MBEC tube formation. Knockdown of Tie2 expression in MBECs significantly inhibited MSC-induced tube formation. Our data indicate MSC treatment of stroke promotes angiogenesis and vascular stabilization, which is at least partially mediated by VEGF/Flk1 and Ang1/Tie2.


2013 ◽  
Vol 21 (2) ◽  
pp. 445-455 ◽  
Author(s):  
Allison Nauta ◽  
Catharina Seidel ◽  
Lorenzo Deveza ◽  
Daniel Montoro ◽  
Monica Grova ◽  
...  

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2316-2316
Author(s):  
Guangxiao Tang ◽  
Gexiu Liu

Abstract INTRODUCTION: Recent studies indicate that transplantation of bone marrow stromal cells after rat traumatic brain injury provided functional recovery. Hypoxia is the major characteristic of ischemic microenvironment. Vascular endothelial growth factor (VEGF) has been demonstrated in vivo and in vitro to be the principal mediator of hypoxia-induced angiogenesis. Recent studies indicate that VEGF implicated in neuroprotection. We tested the hypothesis that hypoxia induces expression of vascular endothelial growth factor (VEGF) in human bone marrow stromal cells (hBMSC) by hypoxia-inducible factor 1 (HIF-1). METHODS: Human bone marrow adherent cells were cultured, and were passaged in DMEM/F12 containing 10% FBS. The fifth passage cells were identified as stromal cells. Subconfluent cells were used, and were cultured with hypoxic DMEM/F12 in hypoxia condition (94% N2 + 1% O2 +5% CO2), and were treated with 50 μM PD98059, or 200 nM wortmannin, or SiRNA specific for HIF-1mRNA. Cells were harvested after 6 h for analysis of active phosphorylated kinases (Akt and MAPK) and the HIF-1-alpha protein or after 24 h for analysis of VEGF protein and mRNA. VEGF mRNA was detected by semi-quantitative RT-PCR, and VEGF protein by ELISA, and kinases and the HIF-1-alpha protein by Western blot. RESULTS: Hypoxia increased significantly level of both VEGF mRNA and VEGF protein in hBMSC s, which were low level in normoxic cultured cells. 24 hours after treatment, ratio of RT-PCR product between VEGF and β-actin reach to (46.25±7.54)% from (19.61±4.57)% of control cells (P<0.01). VEGF protein increased to (142.77±22.33) pg/ml from (45.85±9.69) pg/ml (P<0.01). In addition, hypoxia induced active phosphorylated kinases (Akt and MAPK), and enhanced level of the HIF-1-alpha protein. Moreover, PD98059, or wortmannin, or SiRNA specific for the HIF-1-alpha mRNA inhibited induction of the VEGF gene by hypoxia. CONCLUSION: The expression of VEGF mRNA and VEGF increased in human bone marrow stromal cells during hypoxia condition, which is involved in MAP kinase and phosphatidylinositol 3-kinase signaling. These results support that these cells play an important role in therapy of ischemic/hypoxic injury such as cerebral ischemia and myocardial ischemia. The hMSC capacity to increase expression of VEGF may be the key to the benefit provided by transplanted hMSCs in the ischemic injuries.


2006 ◽  
Vol 199 (2) ◽  
pp. 301-310 ◽  
Author(s):  
Christian Schichor ◽  
Tobias Birnbaum ◽  
Nima Etminan ◽  
Oliver Schnell ◽  
Stefan Grau ◽  
...  

Nanoscale ◽  
2020 ◽  
Vol 12 (13) ◽  
pp. 7284-7300 ◽  
Author(s):  
Xiangfeng Li ◽  
Minjun Liu ◽  
Fuying Chen ◽  
Yuyi Wang ◽  
Menglu Wang ◽  
...  

Biomimicking the nanostructure of natural bone apatite to enhance the bioactivity of hydroxyapatite (HA) biomaterials is an eternal topic in the bone regeneration field.


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