Apoptotic Cells Secrete Angiogenic Factors

It is a medical mystery why approaches such as extracorporeal ozone therapy or even photopheresis seem to have therapeutic effects in certain situations.  One possibility is that stressing of cells outside of the body causes formation of apoptotic bodies, with the apoptotic bodies having a therapeutic effect.

The possibility of apoptotic bodies mediating therapeutic effects has been previously suggested in the context of inflammation.  In a recent paper (Herr et al. The supernatant of apoptotic cells causes transcriptional activation of HIF-1 alpha in macrophages via sphingosine-1-phosphate and transforming growth factor-beta. Blood 2009 Jun 23.) apoptotic bodies were demonstrated to stimulate macrophages to secrete angiogenic factors.

The scientists demonstrated that treatment of macrophages and myeloid cells with conditioned media of apoptotic cells resulted in upregulation of the hypoxia inducible factor (HIF-1) in a calcineurin dependent manner.  Mediators of HIF-1 induction were TGF-b and sphinogosine-1-phosphate induced by the apoptotic bodies.

An interesting suggestion is made that tumor apoptotic bodies trigger macrophages to generate angiogenic factors through activation of HIF-1. 

The possibility of apoptotic bodies stimulating angiogenesis may explain the possibility that the company Vasogen was on the right track in doing clinical trials for diseases that would benefit from angiogenesis such as peripheral artery disease.  It may also explain why positive clinical results have been reported in PAD (Di Paolo et al. Extracorporeal blood oxygenation and ozonation (EBOO): a controlled trial in patients with peripheral artery disease. Int J Artif Organ 2005 Oct;28(10):1039-50).