The role of primed and non-primed MSC-derived conditioned media in neuroregeneration

Nikola Hudakova; Dagmar Mudronova; Dana Marcincakova; Lucia Slovinska; Petra Majerova; Marcela Maloveska; Patricia Petrouskova; Filip Humenik; Dasa Cizkova

doi:10.3389/fnmol.2023.1241432

The role of primed and non-primed MSC-derived conditioned media in neuroregeneration

Front Mol Neurosci. 2023 Nov 2:16:1241432. doi: 10.3389/fnmol.2023.1241432. eCollection 2023.

Authors

Nikola Hudakova¹, Dagmar Mudronova², Dana Marcincakova³, Lucia Slovinska⁴, Petra Majerova⁵, Marcela Maloveska¹, Patricia Petrouskova¹, Filip Humenik¹, Dasa Cizkova^{1

5}

Affiliations

¹ Centre of Experimental and Clinical Regenerative Medicine, University of Veterinary Medicine and Pharmacy in Kosice, Košice, Slovakia.
² Department of Microbiology and Immunology, University of Veterinary Medicine and Pharmacy in Kosice, Košice, Slovakia.
³ Department of Pharmacology and Toxicology, University of Veterinary Medicine and Pharmacy in Kosice, Košice, Slovakia.
⁴ Associated Tissue Bank, Faculty of Medicine, Pavol Jozef Safarik University and Luis Pasteur University Hospital, Košice, Slovakia.
⁵ Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovakia.

Abstract

Introduction: With growing significance in nervous system repair, mesenchymal stem cell-derived conditioned media (MSCCM) have been used in cell-free therapies in regenerative medicine. However, the immunomodulatory and neuroregenerative effects of MSCCM and the influence of priming on these effects are still poorly understood.

Methods: In this study, by various methods focused on cell viability, proliferation, neuron-like differentiation, neurite outgrowth, cell migration and regrowth, we demonstrated that MSCCM derived from adipose tissue (AT-MSCCM) and amniotic membrane (AM-MSCCM) had different effects on SH-SY5Y cells.

Results and discussion: AT-MSCCM was found to have a higher proliferative capacity and the ability to impact neurite outgrowth during differentiation, while AM-MSCCM showed more pronounced immunomodulatory activity, migration, and re-growth of SH-SY5Y cells in the scratch model. Furthermore, priming of MSC with pro-inflammatory cytokine (IFN-γ) resulted in different proteomic profiles of conditioned media from both sources, which had the highest effect on SH-SY5Y proliferation and neurite outgrowth in terms of the length of neurites (pAT-MSCCM) compared to the control group (DMEM). Altogether, our results highlight the potential of primed and non-primed MSCCM as a therapeutic tool for neurodegenerative diseases, although some differences must be considered.

Keywords: IFN-γ; MSC; conditioned medium; neurotrophic effect; priming.

Grants and funding

This study was supported by APVV-19-0193 (DC), VEGA 1/0376/20 (DC), VEGA 2/0129/21 (PM). This work was supported by National Laboratory for Pesticides of the University of Veterinary Medicine and Pharmacy in Kosice, Slovakia.