Neuronal induction and bioenergetics characterization of human forearm adipose stem cells from Parkinson's disease patients and healthy controls.

Ingrid González-Casacuberta,Laura Valls-Roca,Maria Josep Martí,Ester Tobías,Glòria Garrabou,Francesc Cardellach,Claustre Pont-Sunyer,Dolores Vilas,Josep Maria Grau-Junyent,Judith Cantó-Santos,Constanza Morén,Francesc Josep García-García,Gianpaolo Papaccio

doi:10.1371/journal.pone.0265256

Abstract

Neurodegenerative diseases, such as Parkinson’s disease, are heterogeneous disorders with a multifactorial nature involving impaired bioenergetics. Stem-regenerative medicine and bioenergetics have been proposed as promising therapeutic targets in the neurologic field. The rationale of the present study was to assess the potential of human-derived adipose stem cells (hASCs) to transdifferentiate into neuronal-like cells (NhASCs and neurospheres) and explore the hASC bioenergetic profile. hASC neuronal transdifferentiation was performed through neurobasal media and differentiation factor exposure. High resolution respirometry was assessed. Increased MAP-2 neuronal marker protein expression upon neuronal induction (p<0.05 undifferentiated hASCs vs. 28–36 days of differentiation) and increased bIII-tubulin neuronal marker protein expression upon neuronal induction (p<0.05 undifferentiated hASCs vs. 6-28-36 days of differentiation) were found. The bioenergetic profile was detectable through high-resolution respirometry approaches in hASCs but did not lead to differential oxidative capacity rates in healthy or clinically diagnosed PD-hASCs. We confirmed the capability of transdifferentiation to the neuronal-like profile of hASCs derived from the forearms of human subjects and characterized the bioenergetic profile. Suboptimal maximal respiratory capacity trends in PD were found. Neuronal induction leading to positive neuronal protein expression markers is a relevant issue that encourages the suitability of NhASC models in neurodegeneration.

Highlights

Neurodegenerative diseases, including Parkinson’s disease (PD), Alzheimer’s disease, or amyotrophic lateral sclerosis (ALS), are heterogeneous disorders with multifactorial pathogenesis and etiologies
BIII tubulin neuronal marker staining in undifferentiated human-derived adipose stem cells (hASCs) did not lead to a detectable signal (Fig 1 bottom left panel), whereas the signal was present in hASC-exposed neurobasal differentiation media after 20 days of differentiation (Fig 1, bottom middle panel)
Despite the lack of significant differences in respirometry measurements, trends toward suboptimal maximal respiration capacity in PD hASCs were confirmed in both oxygraphs compared with the healthy control hASC lines

Summary

Introduction

Neurodegenerative diseases, including Parkinson’s disease (PD), Alzheimer’s disease, or amyotrophic lateral sclerosis (ALS), are heterogeneous disorders with multifactorial pathogenesis and etiologies. Their prevalence is increasing with the rise of global population and lifespan. Even though many therapeutic approaches have been tested, there are currently no effective preventive or precise treatment options. The multifactorial nature of such disorders includes different molecular pathways related to impaired bioenergetics. Mitochondrial dysfunction, directly implicated in cell bioenergetics, is emerging as a key feature in the etiopathogenesis of these age-related neurodegenerative diseases. Previous findings of our group demonstrated suboptimal bioenergetic profiles in fibroblast models derived from different genetic forms of PD patients [1–3]

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Conclusion