title: Effects of allogeneic bone marrow derived mesenchymal stromal cell therapy on voiding function in a rat model of Parkinson disease.
abstract: OBJECTIVE
  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.
  
  
  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.
authors: Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina; Department of Urology, New York University, New York, New York. Electronic address: lcampeau@jgh.mcgill.ca.
authors: Lysanne
authors: L
authors: Campeau
authors: Division of Urology, Federal University of São Paulo, São Paulo, Brazil.
authors: Roberto
authors: R
authors: Soler
authors: Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
authors: Sivanandane
authors: S
authors: Sittadjody
authors: Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
authors: Rajesh
authors: R
authors: Pareta
authors: Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina; Department of Urology, Fukushima Medical University School of Medicine, Fukushima City, Japan.
authors: Masanori
authors: M
authors: Nomiya
authors: Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
authors: Mona
authors: M
authors: Zarifpour
authors: Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
authors: Emmanuel C
authors: EC
authors: Opara
authors: Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
authors: James J
authors: JJ
authors: Yoo
authors: Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
authors: Karl-Erik
authors: KE
authors: Andersson
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000503:physiopathology*; D064987:Cell- and Tissue-Based Therapy; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D007150:Immunohistochemistry; D045164:Mesenchymal Stem Cell Transplantation; D018613:Microscopy, Confocal; D016627:Oxidopamine; D010300:Parkinson Disease / Q000503:physiopathology* / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000503:physiopathology; D014563:Urodynamics
chemical_list: D016627:Oxidopamine
keywords: Parkinson disease; mesenchymal stromal cells; neurogenic; substantia nigra; urinary bladder; urodynamics