New regulators of angiogenesis

Problem

Problem 1.
A significant number of tumors do not respond to therapies against known or canonical pro-angiogenic factors such as VEGF or VEGFR. Highly vascularized tumors such as glioblastomas are particularly difficult to treat using existing anti-angiogenic therapies. Limiting the chronic formation of blood vessels is is imperative for inhibiting chronic inflammation that drives chronic wound healing and tissue destruction.
Problem 2. Cell replacement approaches are often unsuccessful due to the inability of reprogrammed target cells to integrate into damaged hypoxic tissue, due to a lack of blood vessels that supply nutrients and oxygen. The vascularity must also be controlled to avoid unwanted chronic tissue remodeling. Regulating blood vessel formation is imperative for promoting an organized balance of tissue repair and organ regeneration, required for cell replacement therapy.
The re-vascularization of damaged tissue is essential to promote the proper integration of reprogrammed cells into the damaged tissue.
Solution. We propose the correct and controlled regulation of TMEM230, a membrane protein that controls both the formation and the destruction of new blood vessels, the intravasation and extravasation of leukocytes and factors that induce inflammation and vesicle trafficking, can eliminate the limitations associated with existing clinical treatments and promote the re-vascularization of damaged tissue for regenerative medicine and anti-angiogenic therapies that do not respond to anti VEGF or VEGFR treatments.

Killer Application

We have developed an RNA and protein expression system to modulate TMEM230 expression levels in patient-derived iPSCs or in iPSC-derived 3D organoids for disease modelling, and clinical applications in personalized medicine and bio-engineering.
Potential client applications can include:
1. Clinical applications for iPSC, cell or tissue replacement therapy for patients with chronic disease or acute injury.
2. Ex situ 3D models for disease research and drug screening in precision and personalized medicine to Identify new markers and target genes in inflammation, autoimmunity and circulating tumor cells.
3. We are evaluating TMEM230 modulated expression in 3D organoid co-cultures in promoting controlled formation of new blood vessels for effective integration of stem cell generated organoids in cell replacement therapies and personalized regenerative medicine.

Advantages

Loss of the balance between the formation and destruction of new blood vessels, the intra- and extra-vasation of leukocyte cells and inflammation inducing factors and associated vesicles can be re-established by controlled regulation of TMEM230 protein levels in cells.
Regulated control of TMEM230 includes both regulated repression or stimulation of angiogenesis.

Repression of angiogenesis: Limiting new blood formation will not only inhibit systemic inflammation, circulation of pathogens, cytotoxic factors that inducing chronic inflammation in the body, but also destructive tissue remodeling induced by excessive blood formation and consequential fibrosis or granuloma formation.

Stimulation of angiogenesis: Successful transplantation of iPSC generated 3D organoids for tissue or cell replacement therapies may benefit by re-vascularizing damaged tissue with TMEM230 expression.

TRL