Effects of Allogeneic Bone Marrow Derived Mesenchymal Stromal Cell Therapy on Voiding Function in a Rat Model of Parkinson Disease

Effects of Allogeneic Bone Marrow Derived Mesenchymal Stromal Cell Therapy on Voiding Function in a Rat Model of Parkinson Disease

Author Campeau, Lysanne Google Scholar
Soler, Roberto Autor UNIFESP Google Scholar
Sittadjody, Sivanandane Google Scholar
Pareta, Rajesh Google Scholar
Nomiya, Masanori Google Scholar
Zarifpour, Mona Google Scholar
Opara, Emmanuel C. Google Scholar
Yoo, James J. Google Scholar
Andersson, Karl-Erik Google Scholar
Institution Wake Forest Univ
NYU
Universidade Federal de São Paulo (UNIFESP)
Fukushima Med Univ
Abstract Purpose: Cellular therapy induced transient urodynamic improvement in a rat model of Parkinson disease in which bladder dysfunction was noted after unilateral injection of 6-hydroxydopamine into the medial forebrain bundle. We sought to prolong the effect by injecting allogeneic rat bone marrow mesenchymal stromal cells before and after microencapsulation into the substantia nigra pars compacta.Materials and Methods: Female rats underwent unilateral stereotactic injection of 6-hydroxydopamine in the medial forebrain bundle. Injection was performed in the ipsilateral substantia nigra pars compacta using vehicle alone or vehicle with nonmicroencapsulated or microencapsulated rat bone marrow derived mesenchymal stromal cells. Rats were evaluated by cystometry 7, 14, 28 and 42 days after treatment. Brains were extracted for immunostaining.Results: At 42 days the nonmicroencapsulated group had lower threshold and intermicturition pressure, spontaneous activity and AUC than vehicle treated animals. Rats that received microencapsulated cells had lower threshold pressure at 28 days and lower spontaneous activity at 42 days than vehicle treated rats. Microencapsulated and nonmicroencapsulated rat bone marrow derived mesenchymal stromal cells were noted in the substantia nigra pars compacta up to 42 days after transplantation. At 42 days tyrosine hydroxylase positive neurons were more numerous in the substantia nigra pars compacta of the nonmicroencapsulated group, followed by the microencapsulated and vehicle treated groups.Conclusions: Urodynamic effects of the 6-hydroxydopamine lesion persisted up to 42 days after vehicle injection. Transplantation of nonmicroencapsulated rat bone marrow derived mesenchymal stromal cells improved urodynamic pressure by 42 days after treatment more markedly than microencapsulated cells. This was associated with more tyrosine hydroxylase positive neurons in the treated substantia nigra pars compacta of the nonmicroencapsulated group, suggesting that functional improvement requires a juxtacrine effect.
Keywords urinary bladder, neurogenic
Parkinson disease
mesenchymal stromal cells
urodynamics
substantia nigra
Language English
Sponsor American Urological Association Foundation
American Urological Association Southeastern Section Research Scholar Endowment Fund
Date 2014-03-01
Published in Journal of Urology. New York: Elsevier B.V., v. 191, n. 3, p. 850-859, 2014.
ISSN 0022-5347 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 850-859
Origin http://dx.doi.org/10.1016/j.juro.2013.08.026
Access rights Closed access
Type Article
Web of Science ID WOS:000331123400096
URI http://repositorio.unifesp.br/handle/11600/37493

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