Amniotic membrane preparations and purified compositions and anti-angiogenesis treatment
Compositions having a combination of specific biological components have been found to exert a number of useful effects in mammalian cells, including modulating TGF β signaling, apoptosis, and proliferation of mammalian cells, as well as decreasing inflammation in mice. These components can be obtained commercially, or can be prepared from biological tissues such as placental tissues. Placental amniotic membrane (AM) preparations described herein include AM pieces, AM extracts, AM jelly, AM stroma, and mixtures of these compositions with additional components. The compositions can be used to treat various diseases, such as wound healing, inflammation and angiogenesis-related diseases.
1. A method for reducing angiogenesis in a subject in need thereof comprising, administering to the subject a pharmaceutical composition comprising:
(a) an AM preparation prepared from pulverized or ground amniotic membrane isolated from frozen or previously frozen placenta comprising:
(i) high molecular weight hyaluronan (HA) that is cross-linked by a covalent bond to the heavy chain of inter-α-trypsin inhibitor (IαI), the high molecular weight HA having a molecular weight greater than 1000 kDa;
(ii) tumor necrosis factor-stimulated gene 6 (TSG-6);
(iii) pentraxin (PTX-3); and
(iv) thrombospondin (TSP-1); and
(b) a pharmaceutically acceptable diluent, excipient, or carrier;
wherein the ratio of total protein to HA in the composition is less than 100 parts total protein to 1 part HA; and wherein angiogenesis is reduced.
2. The method of claim 1 , wherein the composition further comprises Smad7.
3. The method of claim 1 , wherein the composition is formulated as a non-solid dosage form or an extended release solid dosage form.
4. The method of claim 1 , wherein the subject is a human.
5. The method of claim 1 , wherein the subject has been diagnosed with a cancer.
6. The method of claim 1 , wherein the subject has been diagnosed with age-related macular degeneration.
7. The method of claim 1 , wherein the composition:
(a). induces apoptosis in an endothelial cell involved in vascular formation;
(b). prevents migration of an endothelial cell involved in vascular formation; and
(c). prevents tube formation of endothelial cells involved in vascular formation.