Evaluation of Neurosecretome from Mesenchymal Stem Cells Encapsulated in Silk Fibroin Hydrogels

Abstract

Physical and cognitive disabilities are hallmarks of a variety of neurological diseases. Stem cell-based therapies are promising solutions to neuroprotect and repair the injured brain and overcome the limited capacity of the central nervous system to recover from damage. It is widely accepted that most benefits of different exogenously transplanted stem cells rely on the secretion of different factors and biomolecules that modulate inflammation, cell death and repair processes in the damaged host tissue. However, few cells survive in cerebral tissue after transplantation, diminishing the therapeutic efficacy. As general rule, cell encapsulation in natural and artificial polymers increases the in vivo engraftment of the transplanted cells. However, we have ignored the consequences of such encapsulation on the secretory activity of these cells. In this study, we investigated the biological compatibility between silk fibroin hydrogels and stem cells of mesenchymal origin, a cell population that has gained increasing attention and popularity in regenerative medicine. Although the survival of mesenchymal stem cells was not affected inside hydrogels, this biomaterial format caused adhesion and proliferation deficits and impaired secretion of several angiogenic, chemoattractant and neurogenic factors while concurrently potentiating the anti-inflammatory capacity of this cell population through a massive release of TGF-Beta-1. Our results set a milestone for the exploration of engineering polymers to modulate the secretory activity of stem cell-based therapies for neurological disorders.

Biomimetic microenvironmental preconditioning enhance neuroprotective properties of human mesenchymal stem cells derived from Wharton's Jelly (WJ-MSCs)

“…It was proved that regeneration of bone and cartilage after application of MSCs combined with biomaterials takes place due to tissue replacement 44 – 46 . In case of neurological disorders, replacement mechanism of regeneration is disputable, however neuro-therapeutic potential of MSCs applied within hydrogel was observed due to their secretory properties, such as production of immunomodulatory or neurogenic factors 47 .…”

Silk Fibroin: An Ancient Material for Repairing the Injured Nervous System

“…It has been found that SF polymer concentrations greater than 2% considerably reduced the viability of MSC in the interior of SF hydrogels, probably due to an excessive compartmentalization [ 63 ]. In addition, this combination of MSC and 2% SF hydrogels induced functional recovery in a stroke mouse model [ 62 ], probably due to the anti-inflammatory properties of MSC, which were strongly stimulated after encapsulation [ 91 ]. The analysis of SF hydrogels in concentrations higher than 2% has been done in composites with gelatin—glycidyl methacrylate.…”

Biotechnology and Biomaterial-Based Therapeutic Strategies for Age-Related Macular Degeneration. Part II: Cell and Tissue Engineering Therapies

“…A very promising biomaterial is silkworm silk fibroin, because it fulfills all the above requirements. The encapsulation of mesenchymal stem cells in silk fibroin hydrogels promotes a substantial release of anti-inflammatory and anti-oxidant molecules with marked neuroregenerative and neuroprotective properties that could be used in AMD treatment ( Martín-Martín et al, 2019 ; Jemni Damer et al, 2020 ).…”