González-Casacuberta Ingrid, Vilas Dolores, Pont-Sunyer Claustre, Tobías Ester, Cantó-Santos Judith, Valls-Roca Laura, García-García Francesc Josep, Garrabou Glòria, Grau-Junyent Josep Maria, Martí Maria Josep, Cardellach Francesc, Morén Constanza
Cellex-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Faculty of Medicine and Health Science, University of Barcelona, Spain.
Internal Medicine Department, Hospital Clínic of Barcelona, Barcelona, Spain.
PLoS One. 2022 Mar 15;17(3):e0265256. doi: 10.1371/journal.pone.0265256. eCollection 2022.
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.
神经退行性疾病,如帕金森病,是具有多因素性质的异质性疾病,涉及生物能量代谢受损。干细胞再生医学和生物能量学已被提议作为神经领域有前景的治疗靶点。本研究的基本原理是评估人源脂肪干细胞(hASC)向神经元样细胞(NhASC和神经球)转分化的潜力,并探索hASC的生物能量学特征。通过神经基础培养基和暴露于分化因子来进行hASC的神经元转分化。评估了高分辨率呼吸测定法。发现神经元诱导后MAP-2神经元标记蛋白表达增加(未分化的hASC与分化28 - 36天相比,p<0.05),以及神经元诱导后βIII-微管蛋白神经元标记蛋白表达增加(未分化的hASC与分化6 - 28 - 36天相比,p<0.05)。通过高分辨率呼吸测定法可检测到hASC的生物能量学特征,但在健康或临床诊断为帕金森病的hASC中未导致氧化能力速率的差异。我们证实了源自人类受试者前臂的hASC向神经元样特征转分化的能力,并对其生物能量学特征进行了表征。发现帕金森病患者存在次优的最大呼吸能力趋势。导致神经元蛋白表达标记呈阳性的神经元诱导是一个相关问题,这鼓励了NhASC模型在神经退行性变研究中的适用性。
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