PyNTTTTGT Oligonucleotides as Tool in Tissue repair Procedures

MONTANER AD; HERNANDO INSÚA A; ELÍAS F; CORONEL F; DENICHILO A; RODRIGUEZ JM; FLÓ J; LÓPEZ RA; MATZKIN B; CHASSEING NA; VILLAR M; ZORZOPULOS J

Queensland

Congreso; 5th ISSCR Annual Meeting; 2007

International Society for Stem Cell Research (ISSCR)

It was recently discovered that immunostimulatory oligonucleotides (ODNs) of the PyNTTTTGT class are potent stimulators for Bone Marrow (BM)-derived adult Mesenchymal Stem Cells (MSCs) expansion. The capacity to increase the number of MSC in vivo both in BM and in peripheral blood, suggested their potential in tissue repair therapies. Regarding this, we have now found that treatment with IMT504, the prototype of PyNTTTTGT ODNs, resulted in considerable improvement of three disease models in rats: neuropathic pain, osteoporosis and multiply organ failure associated to sepsis. In a neuropatic pain model induced by sciatic nerve crush, we evaluated the development of mechanical and thermal allodynia. Animals receiving IMT504 or MSC treatment did not develop mechanical allodynia and presented a significantly lower number of nociceptive responses when compared to controls. In an osteoporosis model of ovariectomyzed rats, we evaluated the progressive bone loss of the trabecular bone density. Treatment with IMT504 considerably improves bone quality and formation. In a sepsis model induced by bacterial administration, IMT504-treatment improved the organ conditions and drop off factors related to the disseminated intravascular coagulation, frequently associated with the septic shock. These multiple activities of IMT504 suggest their action on a vital center of homeostatic maintenance which coordinates not only the immunological defense against the aggression but also the subsequent tissue repair process stimulated by the damage produced by the aggression itself and/or by the associated defensive inflammatory process. Clinical trials will soon asses the possibility of its medical use. Por este trabajo se me otorgo el "ISSCR Junior Scientific Travel Award 2007"