Myoblast-mediated gene therapy via encephalomyosynangiosis--a novel strategy for local delivery of gene products to the brain surface.

Abstract:

:An encephalomyosynangiosis (EMS) is a temporal muscle graft that is placed onto the surface of the brain to serve as a source for collateral vessel growth for brain revascularization in patients with Moyamoya Disease (MMD). To facilitate an EMS in patients with occlusive cerebrovascular diseases other than MMD, the transfer of pro-angiogenic genes via transplantation of retrovirally transduced myoblasts into the temporal muscle may represent an innovative approach to augment collateralization. Thus, we tested whether retrovirally transfected myoblasts can spontaneously fuse with the non-ischemic and uninjured muscle tissue and if a reporter gene can be stably expressed within the temporal muscle of the EMS. Primary mouse myoblasts expressing a reporter gene were implanted into the temporal muscle prior to an EMS being performed on C57/BL6 mice. Three different implantation modalities were evaluated: (a) intramuscular injection, (b) application of a cell pellet and (c) a combination of both techniques. Myoblast implantation resulted in spontaneous fusion with the host muscle fibers and stable reporter gene expression at both the muscle/brain interface and within the non-ischemic and uninjured temporal muscle in all animals. The mean number of fused hybrid myofibers was 59±28 after injection, 37±30 after pellet application and 60±23 after a combination of both techniques. Regardless of the implantation modality, an abundant extracellular expression of the reporter gene was evident at the muscle/brain interface; in the case of myoblast delivery by injection, expression was also observed around the needle tract marking the implantation site. This method could be used in the future to deliver angiogenic growth factors to the muscle/brain interface in order to improve revascularization after an EMS.

journal_name

J Neurosci Methods

authors

Hecht N,Peña-Tapia P,Vinci M,von Degenfeld G,Woitzik J,Vajkoczy P

doi

10.1016/j.jneumeth.2011.07.011

subject

Has Abstract

pub_date

2011-09-30 00:00:00

pages

61-6

issue

1

eissn

0165-0270

issn

1872-678X

pii

S0165-0270(11)00416-X

journal_volume

201

pub_type

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