Cell secretome based approaches in Parkinson’s disease regenerative medicine

ABSTRACT

Introduction: The available therapeutic strategies for Parkinson’s disease (PD) rely only on the amelioration of the symptomatology of the disease, lacking neuroprotection or neuroregeneration capacities. Therefore, the development of disease modifying strategies is extremely important for the management of PD in the long term.

Areas covered: In this review, the authors provide an overview of the current therapeutic approaches for PD and the emerging use of stem cell transplantation as an alternative. Particularly, the use of the secretome from mesenchymal stem cells (MSCs), as well as some methodologies used for the modulation of their paracrine signaling, will be discussed. Indeed, there is a growing body of literature highlighting the use of paracrine factors and vesicles secreted from different cell populations, for this purpose.

Expert opinion: Secretome from MSCs has shown its potential as a therapy for PD. Nevertheless, in the coming years, research should focus in several key aspects to enable the translation of this strategy from the bench to the bedside.

KEYWORDS:

• Biomaterials
• bioreactors
• dopamine
• dopaminergic neurons
• hypoxia
• mesenchymal stem cells
• neural derived cells
• Parkinson’s disease
• secretome

Article highlights

• The available therapeutic strategies for Parkinson’s disease do not impact disease progression, imposing the need for innovative therapeutic approaches.

• The use of stem cells has emerged as a promising approach for regenerative medicine.

• Cell sources such as embryonic stem cells, induced pluripotent stem cells, neural stem cells, or mesenchymal stem cells are some of the most promising to replacement strategies.

• The secretome of some cell populations is now accepted as their main therapeutic action.

• The secretome can be modulated at intracellular and extracellular levels with the purpose to potentiate its benefits.

• The potential of the secretome in Parkinson’s disease encourages the development of cell-free products over cell transplantation strategies.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This work was supported by Portuguese Foundation for Science and Technology (FCT): Ciência 2007 Program and IF Development Grant [IF/00111/2013] to AJ Salgado, PhD scholarships attributed to C.R. Marques [PD/BDE/127833/2016], A. Marote [PDE/BDE/113598/2015] and B. Mendes-Pinheiro [SFRH/BD/120124/2016] and Post-Doctoral Fellowship to F.G. Teixeira [SFRH/BPD/118408/2016]. This article has been developed under the scope of the project NORTE-01-0145-FEDER-000023, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). This work has been funded by FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through FCT, under the scope of the project [POCI-01-0145-FEDER-007038].