Loop peptide and TGF.alpha. for stimulating stem cell proliferation and migration

Patent Number: 7,365,172

Stem cells need to be maintained in a quiescent state when they are not needed to make new cells.  This is because if stem cells were consistently proliferating then there would be a high propability of mutations, thus leading to cancer.  One of the methods that stem cells maintain themselves in a non-proliferating state is through autocrine secretion of inhibitory factors.  One such main autoinhibitory factors is Transforming Growth Factor (TGF)-beta.  This is why patents, such as US patent #6627191 cover the use of neutralizing antibodies to TGF-beta as a means of hematopoietic stem cell stimulation.  The autocrine inhibitory properties of TGF-beta are not restricted to hematopoietic stem cells, for example, antibodies to TGF-beta stimulate hepatic regeneration, theoretically by inhibiting the autoinhibitory effects of TGF-beta.  Of course the arguement can be made that liver stem cells are related to bone marrow stem cells, therefore this is not surprising.  Hematopoietic stem cell markers such as CD133 are also found on liver stem cells.  Additionally, bone marrow stem cells have been demonstrated to induce clinical improvement in patients with liver failure.

While TGF-beta has inhibitory activities on stem cells, TGF-alpha has the opposite effects.  Specifically, TGF-alpha is a member of the epidermal growth factor (EGF) family of cytokines and binds the EGF-receptor.  EGF for example, stimulates mesenchymal stem cell activity and induces resistance to apoptosis.  EGF family members, along with gastrin, have also been demonstrated to induce activation of endogenous pancreatic precursors. 

TGF-alpha has the following regenerative activities
- stimulates migration and proliferation of neural progenitor cells in animal models of Parkinson's
- age-related loss in production associated with decreased olfactory neurogenesis
- associated with wound healing

The current patent covers composition of matter on TGF-alpha mimetic peptides. 

In other words, for people who would like to induce biological effects similar to those induced by TGF-beta clinically, the patent is very useful since peptide mimetics are easier to make, and have a better pharmacology than administration of proteins.

View this patent on the USPTO website.