Angiocrine Bioscience’s technology is based on key breakthroughs in vascular biology and stem cell research.

What are endothelial cells (ECs)?

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In the human body nearly all tissues depend on blood supply, and the blood supply depends on endothelial cells, which are the cells that form the linings of all the blood vessels in our body.  Their most basic function is to control the passage of materials into and out of the bloodstream.  Endothelial cells also have a remarkable capacity to adjust to their local environment and provide an additional role of extending and remodeling the network of blood vessels, tissue growth and repair.  Over the last several decades, the functions of the endothelial cells were understood to be broader and broader.  For example, they are a key player in initiating clots when vessels become damaged.  They are also capable of guiding the immune system to sites of infection.  As our understanding grows, these cells once described as simple “cellophane” are now appreciated as being “orchestral maestros” regulating organ health.

Why are endothelial cells so important?

The most recent realization in endothelial cell biology is recognition of their role to restore, regenerate and repair damaged tissues and organs.  As a result of damage or injury, endothelial cells begin a process whereby they direct and support neighboring stem cells – the undifferentiated cells in our body from which all other cells with specialized functions are derived.  The repair process is mediated via Angiocrine factors, which are growth factors specifically from endothelial cells. When given the proper instruction stem cells will either become new stem cells (self-renewal) or become specialized cells such as blood cells, brain cells, heart muscle cells or bone cells.  Overall, this cross-talk ensures that the tissues and the blood vessels grow in unison.

Successful tissue growth and repair must be coordinated with vessel growth.

What are vascular niches?

Endothelial cells and adult stem cells congregate to form a “vascular niche” at specific locations in the body where this regenerative process occurs to combat disease or repair damage.  These niches have been found in nearly all tissues; intestines, liver, hair follicles, bone marrow, brain, etc. Within the vascular niche, the relationship between the endothelial cells and stem cells is very dynamic and regulated, with endothelial cells communicating with stem cells through chemical messengers called angiocrine factors, as well as through direct cell-to-cell contact.

Why can’t natural endothelial cells be used as therapeutics?

The potential use of natural endothelial cells as therapeutics has been hampered by the difficulty in growing ECs reliably and robustly outside the body. In addition, natural ECs grown outside the body are from dormant vessels, and thus are NOT actively promoting stem cells. This challenge led Angiocrine to develop E-CEL in order to overcome these limitations.

Genetically modified endothelial cells (E-CEL®) have therapeutic properties

Angiocrine Bioscience has developed genetically modified umbilical vein endothelial (E-CEL®) cells using proprietary engineering technologies that simulate niche ECs in the body and overcome the limitations of non-engineered ECs for use as therapeutic agents. All E-CEL cells have a genetic modification consisting of a pro-survival gene (found in nature) which is inserted into the DNA of the endothelial cells via a clinically proven method of viral transduction.  Organ/indication-specific E-CEL cells have a second gene insertion which orients the E-CEL cells towards a specific tissue or organ.

Advantages of E-CEL®  cells:

  • Survive and grow outside the body with improved stability and growth characteristics compared to natural ECs
  • Are in an activated state, capable of directing, communicating with, and interacting with stem cells
    • Secrete tissue-specific chemical messengers (i.e. angiocrines) that initiate tissue regeneration
    • Increase (expand) the number of stem cells
  • Activate other important cells involved in restoring, regenerating, and repairing tissue
  • Mimic the function of natural ECs
  • In pre-clinical studies, E-CEL® cells have been demonstrated to be transient in vivo, thus greatly reducing the risk of long-term adverse effects from genetic modification

Preclinical Studies

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.

E-Cel Treatment

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.

In a 6-week toxicology study in mice, E-Cell® cells (at doses up to 10-times the highest anticipated human dose) produced no safety signal (ie, no deaths, clinical observations, hematology or clinical chemistry findings, changes in organ weights, or macroscopic or microscopic pathology findings).

In summary, E-CEL® cells have the potential to establish a vascular niche in damaged organs and tissues to restore (eg, hematology/immune function after chemotherapy, hematopoietic function after hematopoietic stem cell transplantation [HSCT]), regenerate (eg, gastrointestinal function, lung function, neural function, wound healing without scarring and fibrosis), and repair (eg, tendon damage, degenerated discs).

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