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Platelet rich plasma and losartan for the treatment of muscle injuries

Grant number: 11/09687-3
Support Opportunities:Regular Research Grants
Start date: August 01, 2011
End date: January 31, 2014
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Rene Jorge Abdalla
Grantee:Rene Jorge Abdalla
Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Associated researchers: Priscila Martins Andrade Denapoli ; Roberta Sessa Stilhano Yamaguchi ; Sang Won Han ; Sheila Jean McNeill Ingham

Abstract

Muscle injuries account for a large number of all injuries sustained by participants in sports and constitute between 10% and 55% of all injuries. Although muscles can undergo regeneration after injury, the healing process is slow and often culminates in incomplete functional recovery and fibrosis. The formation of dense scar tissue can impair muscle function and lead to muscle contracture and chronic pain. Despite the considerable medical need, there has been relatively little progress in the development of therapeutic approaches to enhance healing following muscle injury. One of the new treatments tried in the clinical setting is the use of platelet rich plasma (PRP) that can be defined as a fraction of the blood plasma that has a higher platelet concentration than normal blood. Nonetheless, as PRP contains TGF-b, a known pro-fibrotic agent, its use could lead to a higher degree of fibrosis during muscle healing.Aim #1 of this study is to evaluate muscle healing in a murine model after a contusion injury and treatement with PRP and with PRP after TGF-b is bloqued. We hipothesize that animals that receive PRP with TGF-b blockade will present with better healing. For this, the animals will be submitted to a previously described contusion injury and the TGF-b will be removed from the PRP with the use of magnetic beads with anti- TGF-b antibodies or the animals will receive losartan, an agiotenin II receptor blocker that also acts as a TGF-b blocker. The outcomes evaluated will be: muscle strength, histology and immuno-histochemistry.Aim #2 of this study is to evaluate, in vitro, the angiogenic activity and fibrosis of PRP, PRP with the TGF-b removed and PRP + losartan. For this cells will be grown in these different media and factor expression will be measured by RT-PCR. We hipothesize that the cells with PRP will have a greater expression of angiogenic and fibrotic factors while the cells grown in the media with PRP and no TGF-b will only show an increase in angiogenic factors. (AU)

Articles published in Agência FAPESP Newsletter about the research grant:
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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
STILHANO, ROBERTA SESSA; ANDRADE DENAPOLI, PRISCILA MARTINS; GALLO, CAMILA CONGENTINO; SAMOTO, VIVIAN YOCHIKO; MCNEILL INGHAM, SHEILA JEAN; ABDALLA, RENE JORGE; KOH, TIMOTHY JON; HAN, SANG WON. Regenerative effect of platelet-rich plasma in the murine ischemic limbs. Life Sciences, v. 284, . (15/20206-8, 11/09687-3)
ANDRADE DENAPOLI, PRISCILA MARTINS; STILHANO, ROBERTA SESSA; MCNEILL INGHAM, SHEILA JEAN; HAN, SANG WON; ABDALLA, RENE JORGE. Platelet-Rich Plasma in a Murine Model: Leukocytes, Growth Factors, Flt-1, and Muscle Healing. AMERICAN JOURNAL OF SPORTS MEDICINE, v. 44, n. 8, p. 1962-1971, . (11/09687-3)