scholarly journals Therapeutic vascular growth in the heart

2019 ◽  
Vol 1 (1) ◽  
pp. H9-H15
Author(s):  
Ebba Brakenhielm ◽  
Vincent Richard

Despite tremendous efforts in preclinical research over the last decades, the clinical translation of therapeutic angiogenesis to grow stable and functional blood vessels in patients with ischemic diseases continues to prove challenging. In this mini review, we briefly present the current main approaches applied to improve pro-angiogenic therapies. Specific examples from research on therapeutic cardiac angiogenesis and arteriogenesis will be discussed, and finally some suggestions for future therapeutic developments will be presented.

2017 ◽  
Vol 30 (3) ◽  
pp. 159-163
Author(s):  
Tania Bubela ◽  
Yael Mansour ◽  
Dianne Nicol

Genome editing technologies promise therapeutic advances for genetic diseases. We discuss the ethical and societal issues raised by these technologies, including their use in preclinical research, their potential to address mutations in somatic cells, and their potential to make germ line alterations that may be passed to subsequent generations. We call for a proportionate response from health leaders based on a realistic assessment of benefits, risks, and timelines for clinical translation.


Author(s):  
Junya Suzuki ◽  
Yuuki Shimizu ◽  
Kazuhito Tsuzuki ◽  
Zhongyue Pu ◽  
Shingo Narita ◽  
...  

Therapeutic angiogenesis with autologous stem/progenitor cells is a promising novel strategy for treatment of severe ischemic diseases. Human clinical trials utilizing autologous adipose-derived regenerative cells (ADRCs) have not reported treatment-related critical adverse effects thus far. However, there is still a large knowledge gap whether treatment of ischemic diseases with angiogenic therapy using ADRCs would promote unfavorable angiogenesis associated with tumors in vivo. Herein, we addressed this clinical question using a mouse hind limb ischemia (HLI) and simultaneous remote tumor implantation model. C57BL/6J background wild-type mice were injected with murine B16F10 melanoma cells on their back, one day before ischemic surgery. These mice were subjected to surgical unilateral hindlimb ischemia, followed by ADRCs implantation or PBS injection into the hindlimb ischemic muscles on the next day. Intramuscular implantation of ADRCs enhanced tissue capillary density and blood flow examined by a laser Doppler blood perfusion analysis in hind limb. However, this therapeutic regimen for ischemic limb using ADRCs did not affect remote melanoma growth nor the density of its feeder artery, angiogenesis and lymphatic vessels compared to the PBS group. In addition, no distant metastases were detected in any of the mice regardless the group. In conclusion, local implantation of ADRCs promotes angiogenesis in response to tissue ischemia in the hind limb without promoting remote tumor growth and related angio/lymphangiogenesis. Therapeutic angiogenesis to the ischemic hind limb using ADRCs seems to be safe regarding remote tumor growth.


2011 ◽  
Vol 39 (6) ◽  
pp. 1644-1648 ◽  
Author(s):  
Roberto Gianni-Barrera ◽  
Marianna Trani ◽  
Silvia Reginato ◽  
Andrea Banfi

Therapeutic angiogenesis is an attractive strategy to treat patients suffering from peripheral or coronary artery disease. VEGF (vascular endothelial growth factor-A) is the fundamental factor controlling vascular growth in both development and postnatal life. The interplay between the VEGF and Notch signalling pathway has been recently found to regulate the morphogenic events leading to the growth of new vessels by sprouting. Angiogenesis can also take place by an alternative process, i.e. intussusception or vascular splitting. However, little is known about its role in therapeutic angiogenesis and its molecular regulation. In the present article, we briefly review how VEGF dose determines the induction of normal or aberrant angiogenesis and the molecular regulation of sprouting angiogenesis by Notch signalling, and compare this process with intussusception.


2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Abraham Lin ◽  
Eline Biscop ◽  
Colum Breen ◽  
Stephen J. Butler ◽  
Evelien Smits ◽  
...  

Non-thermal plasma (NTP), an ionized gas generated at ambient pressure and temperature, has been an emerging technology for medical applications. Through controlled delivery of reactive oxygen and nitrogen species (ROS/RNS), NTP can elicit hormetic cellular responses, thus stimulating broad therapeutic effects. To enable clinical translation of the promising preclinical research into NTP therapy, a deeper understanding of NTP interactions with clinical substrates is profoundly needed. Since NTP-generated ROS/RNS will inevitably interact with blood in several clinical contexts, understanding their stability in this system is crucial. In this study, two medically relevant NTP delivery modalities were used to assess the stability of NTP-generated ROS/RNS in three aqueous solutions with increasing organic complexities: phosphate-buffered saline (PBS), blood plasma (BP), and processed whole blood. NTP-generated RNS collectively (NO2−, ONOO−), H2O2, and ONOO− exclusively were analyzed over time. We demonstrated that NTP-generated RNS and H2O2 were stable in PBS but scavenged by different components of the blood. While RNS remained stable in BP after initial scavenging effects, it was completely reduced in processed whole blood. On the other hand, H2O2 was completely scavenged in both liquids over time. Our previously developed luminescent probe europium(III) was used for precision measurement of ONOO− concentration. NTP-generated ONOO− was detected in all three liquids for up to at least 30 seconds, thus highlighting its therapeutic potential. Based on our results, we discussed the necessary considerations to choose the most optimal NTP modality for delivery of ROS/RNS to and via blood in the clinical context.


2009 ◽  
Vol 28 (2) ◽  
pp. 93-101 ◽  
Author(s):  
Charlene Pollan

Retinopathy of prematurity (ROP) results from the abnormal growth of blood vessels in the vascular bed supporting the developing retina. Estimated to cause up to 500 new cases of blindness in the U.S. each year, ROP affects primarily infants born at less than 1,500 g. Although its etiology is not well understood, ROP is thought to occur as a result of a complex interaction between oxygen and vascular growth factors. This article briefly reviews the history of ROP, discusses its pathophysiology, and addresses the risk factors and strategies for prevention.


2014 ◽  
Vol 42 (6) ◽  
pp. 1637-1642 ◽  
Author(s):  
Roberto Gianni-Barrera ◽  
Mariateresa Bartolomeo ◽  
Brigitte Vollmar ◽  
Valentin Djonov ◽  
Andrea Banfi

Therapeutic angiogenesis is an attractive strategy to treat patients suffering from ischaemic conditions and vascular endothelial growth factor-A (VEGF) is the master regulator of blood vessel growth. However, VEGF can induce either normal or aberrant angiogenesis depending on its dose localized in the microenvironment around each producing cell in vivo and on the balanced stimulation of platelet-derived growth factor-BB (PDGF-BB) signalling, responsible for pericyte recruitment. At the doses required to induce therapeutic benefit, VEGF causes new vascular growth essentially without sprouting, but rather through the alternative process of intussusception, or vascular splitting. In the present article, we briefly review the therapeutic implications of controlling VEGF dose on one hand and pericyte recruitment on the other, as well as the key features of intussusceptive angiogenesis and its regulation.


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