Influence of Different ECM-Like Hydrogels on Neurite Outgrowth Induced by Adipose Tissue-Derived Stem Cells

Abstract

Mesenchymal stem cells (MSCs) have been proposed for spinal cord injury (SCI) applications due to their capacity to secrete growth factors and vesicles—secretome—that impacts important phenomena in SCI regeneration. To improve MSC survival into SCI sites, hydrogels have been used as transplantation vehicles. Herein, we hypothesized if different hydrogels could interact differently with adipose tissue-derived MSCs (ASCs). The efficacy of three natural hydrogels, gellan gum (functionalized with a fibronectin peptide), collagen, and a hydrogel rich in laminin epitopes (NVR-gel) in promoting neuritogenesis (alone and cocultured with ASCs), was evaluated in the present study. Their impact on ASC survival, metabolic activity, and gene expression was also evaluated. Our results indicated that all hydrogels supported ASC survival and viability, being this more evident for the functionalized GG hydrogels. Moreover, the presence of different ECM-derived biological cues within the hydrogels appears to differently affect the mRNA levels of growth factors involved in neuronal survival, differentiation, and axonal outgrowth. All the hydrogel-based systems supported axonal growth mediated by ASCs, but this effect was more robust in functionalized GG. The data herein presented highlights the importance of biological cues within hydrogel-based biomaterials as possible modulators of ASC secretome and its effects for SCI applications.

Intra-Articular Injection of 2 Different Dosages of Autologous and Allogeneic Bone Marrow- and Umbilical Cord-Derived Mesenchymal Stem Cells Triggers a Variable Inflammatory Response of the Fetlock Joint on 12 Sound Experimental Horses

“…Even if only one of the 12 horses (8.3%) in this study (horse 7) exhibited severe signs of pain and inflammation, this kind of reaction could be observed on any client-owned animal participating in a clinical trial. Growing evidence indicates that future clinical applications of stem cell therapies will not aim at injecting MSCs alone or simply diluted in PBS but rather suggests that MSCs would gain therapeutic interest if combined with extracellular matrix substitutes like hydrogels in order to enhance their viability and metabolic activity [23, 38]. Recent studies even indicate that the therapeutic activities of MSCs could be achieved by injecting solely the bioactive secretory factors of MSCs, called secretome, suggesting a future cell-free/cell-based strategy [23, 39, 40].…”

Exploiting the impact of the secretome of MSCs isolated from different tissue sources on neuronal differentiation and axonal growth

“…Briefly, DRGs from cervical and thoracic regions of the spine of neonatal rat pups (P5) were dissected and the remnants of peripheral nerve processes were cleaned. The explants were placed on top of collagen hydrogels, prepared as previously described [34] and incubated with MSC CM for 7 days. DRG cultures in collagen gels in Neurobasal Medium supplemented with B27, L-glutamine, glucose and 1% of P/S was used as control.…”

“…As previously described [34], DRG axonal growth was inferred by the quantification of the area occupied by the neurites within the collagen gels. For that, after confocal imaging, samples (n ¼ 8/ condition) were analyzed by Image J software.…”

Advances in bioinks and in vivo imaging of biomaterials for CNS applications

“…Combining stem cells with biomaterials is very attractive in this context as biomaterial may shield the cells from this unsupportive milieu [10] or even modify the microenvironment by releasing growth or anti-inflammatory factors [11,12]. Studies show that advantages of using cell-biomaterial composites are extensive including the control over the orientation of cells, enhanced cell viability, proliferation, adhesion [13], differentiation [14], directed migratory behavior [15] and even improved retention of their secretome (secreted bioactive molecules) [16], responsible for their beneficial paracrine functions [17]. Moreover, biomaterials can be tailored in terms of their structure, shape, physicochemical properties and biological performance, among others.…”