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What are endothelial cells (ECs)?
The blood vessels can be considered forming the largest organ in the body and course through every part of the human body. The inner lining of blood vessels is composed of endothelial cells. The smallest of the blood vessels, the capillaries, are composed only of endothelial cells. Capillaries form vascular networks within virtually every organ and thus are vital for normal functioning of organs and a healthy, active life.
Why are endothelial cells so important?
During embryonic development, specialized endothelial cells lead organ development.
In adulthood, endothelial cells in capillaries not only play a critical role in keeping organs functioning and healthy, but also serve an active role in repairing tissue damage by expressing a complex mixture of reparative angiocrine factors. Importantly, virtually every organ contains progenitor (stem) cells alongside its capillaries, forming what is known as the vascular ‘stem cell’ niche.
When a person sustains bodily damage from injury of diseases, the endothelial cells within the niche respond by expressing ‘reparative’ angiocrine factors that guide the neighboring progenitor cells to repair the damaged tissue in the organ.
Successful tissue growth and repair must be coordinated with vessel growth.
What are vascular niches?
Endothelial cells and adult progenitor (stem) cells congregate to form vascular ‘stem cell’ niches. These niches have been found in nearly all tissues and organs. Within the vascular niche, the endothelial cells maintain the organ’s progenitor (stem) cells by expressing ‘maintenance’ angiocrine factors. In some organs, the vascular niches are very active in health. For example, the human body renews the lining of the mouth and the gastro-intestinal (GI) tract on a daily basis. This renewal is produced by the vascular niches in our GI tract. The bone marrow produces billions of cells on a daily basis—another example of very active vascular niches. Other organs like the brain have less active niches; however, the human body retains the capacity to repair and heal virtually every organ through its organ vascular ‘stem cell’ niches.
How does the human body naturally repair itself?
In mammals, although regeneration is quite restricted to a number of tissues and organs, this particular healing process is possible through the existence of tissue-resident stem/progenitor cells and the vascular ‘stem cell’ niche. Upon injury, tissue resident progenitors are activated, they proliferate, migrate, and differentiate into tissue-specific cells and functionally replace the damaged or lost cells. Besides this, blood vessels, especially the micro-vessels within organs, play crucial roles in tissue repair. Endothelial cells, which line blood vessels, together with the resident surrounding cells create a vascular ‘stem cell’ niche which is central to local and distant signaling thereby shaping the reparative and healing process. The signaling from the niche endothelial cells are in the form of angiocrine factors, which can number into the hundreds, are expressed dynamically, and in a two-way communication with the tissue progenitors in the niche.
Ref. Rivera FJ et. al., The Vascular Niche in Tissue Repair (Editorial). Front. Cell Dev. Biol., 29 September 2017
Why don’t we heal well as we get older?
We all know that children have remarkable ability to heal quickly, while our grandparents don’t. In the last two decades, scientists (including ours at Angiocrine) have found that the activity of the body’s vascular niches become diminished as we get older, and often get completely disabled with multitude of diseases. Although both the endothelial cells and the stem cells both diminish with age, it is the former—i.e., endothelial—cells that are most affected with aging. Scientists have shown that age-dependent endothelial dysfunction occurs even in ‘healthy’ elderly people as well as ‘healthy’ aged animals.
What is the E-CEL Platform and E-CEL Therapies?
E-CEL Platform is a proprietary platform technology that is our Research & Development engine to create various Advanced Reparative Medicines which consist of multiple versions of engineered cord endothelial (E-CEL) cells – the active ingredients of E-CEL Therapies. The E-CEL Platform includes use of our proprietary E-CEL Viral Vector to conduct genetic engineering. Also included is our proprietary method of manufacturing, called E-CEL Manufacturing. We currently have two E-CEL Therapy products in clinical testing and five ‘next-generation’ E-CEL Therapies in the research stage of development.
What is the history behind using endothelial cells as a possible means of treating a condition?
In the late 1990s and early 2000s, scientists wondered if vascular endothelial cells can become blood stem cells because of their common embryonic origin. They transplanted lining of aorta and vena cava and injected vascular brain endothelial cells in animals that underwent lethal irradiation. The animals were rescued, but the scientists definitively found out that the rescue was not because endothelial cells became blood stem cells, but from something else. Over the next decade, scientists, including Angiocrine’s, started to deduce that the rescue effect by implanted or injected endothelial cells may be due to the numerous angiocrine factors that the endothelial cells were known to produce. However, that was still a long way from evolving this phenomenon seen in irradiated animals into a therapy that might benefit human patients. It wasn’t until the mid-to-late 2010 when Angiocrine Bioscience and its collaborators, through numerous experimentations and innovations, found a path to create Advanced Reparative Medicines from genetically-modified human endothelial cells.
How did the E-CEL Platform come to being?
One of the technologies behind the E-CEL Platform was found serendipitously by our Scientific Founder, Professor Shahin Rafii of Cornell University. He found that a gene from the adenovirus can act as a ‘pro-survival’ gene, specifically for endothelial cells. He found these genetically-engineered endothelial cells can grow stem cells without exhausting them. There were other discoveries made by Angiocrine Bioscience since the mid 2010s which enabled the creation of the E-CEL Platform, which is now the engine for the company to create and develop various lines of Advanced Reparative Medicines across multiple indications.
Why can’t natural endothelial cells be used as therapeutics?
Human endothelial cells, once isolated from tissues, could die quickly in culture, and are difficult to mass produce for medical use in a reliable manner. Also, depending on the organ to be repaired, may require additional genetic engineering. Angiocrine’s proprietary E-CEL Platform is the world’s first technology platform that overcomes the inherent problems of using cultured primary endothelial cells and enables creation of various lines of Advanced Reparative Medicines.
In animal models of chemo-radiation toxicities (high-dose chemotherapy or total body irradiation), AB-205 demonstrated rejuvenation of various organs (bone marrow, spleen, the gastrointestinal tract) as well as regeneration of organ-specific capillary vasculature, indicating accelerated recovery of organ-specific vascular niches.
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