One therapeutic intervention for neurotrauma and neurodegenerative disease could involve cell replacement with neural progenitor cells that can differentiate and directly aid in reconnection of neuronal circuits and/or replenish lost neurotrophic/neuromodulatory substances. Use of human embryonic stem cells (hESC) and neural stem cells (NSC) from adult or embryonic tissue have been proposed as sources of neural tissue for neurorestorative therapies, yet their widespread clinical use may be limited by logistical and ethical constraints. Additional sources of neural progenitor cells need to be identified and if found in adult peripheral tissues these could be proliferated and used for autologous transplantation. An easily accessible and ample source of progenitor cell with neural characteristics resides in adult adipose; thus the overall goal of this research plan is to explore whether Adipose-Derived Adult Progenitor cells (ADAPs) possess cellular and physiological characteristics that would make them suitable for neurorestorative therapies. This exploratory proposal aims: (1) To characterize (a) the expression profile of neural and glial cellular markers and transcription factors in heterogeneous and clonal populations of ADAPs grown in culture under defined growth-factor supplemented neural differentiation media; (b) the proliferative and transformation potential of ADAPs; and (c) the stability of ADAP neural phenotypes and intracellular calcium responses to depolarizing stimuli. (2) To investigate the survival, migration, and differentiation in vivo of ADAPs after transplantation into rat midbrain or spinal cord using non-invasive bioluminescent imaging tools and ICC; and (3) to assess whether transplants of undifferentiated or neurally differentiated ADAPs can contribute toward functional locomotor recovery of hemi-parkinsonian or spinal cord-lesioned rats. Successful completion of these studies should provide new and critical information to evaluate the potential therapeutic value of this novel neural progenitor population in cell replacement strategies.
| Wrage, Philip C; Tran, Thi; To, Khai et al. (2008) The neuro-glial properties of adipose-derived adult stromal (ADAS) cells are not regulated by Notch 1 and are not derived from neural crest lineage. PLoS One 3:e1453 |
| McCoy, Melissa K; Martinez, Terina N; Ruhn, Kelly A et al. (2008) Autologous transplants of Adipose-Derived Adult Stromal (ADAS) cells afford dopaminergic neuroprotection in a model of Parkinson's disease. Exp Neurol 210:14-29 |
