Bogdan Amuzescu

Extracellular vesicle (EV) preparations have emerged as potentially useful therapeutic tools for various inflammatory or neurodegenerative CNS disorders. Compared to mesenchymal stem cell preparations, they feature enhanced blood–brain barrier permeability and access to injured brain tissue, and better quality assessment and dosing options. A particular case where such therapies may prove beneficial is multiple sclerosis (MS), an autoimmune disease likely triggered by cross-reactivity with some viral antigens, producing an extended demyelinating encephalomyelitis with multiple patchy lesions. Several animal models of MS have been developed, including experimental autoimmune encephalomyelitis (EAE) via injection of myelin oligodendrocyte glycoprotein (MOG) 35–55, inoculation with Theiler’s murine encephalomyelitis virus (TMEV), and the Cuprizone model. Via literature search we retrieved 24 experimental studies on rodent (rat or mouse) MS models with therapeutic administration of native or enhanced EV preparations suitable for this meta-analysis. We found statistically significant mean differences between experimental and control groups for clinical scores (normalized to a 0–5 scale) (−1.21, 95% confidence interval (CI) [−1.49,−0.93] (native EVs); −1.67, CI [−2.28,−1.05] (enhanced EVs)), for pathological scores of inflammation and demyelination, and for several molecular markers of inflammation and myelin repair. These results point to the need for clinical translation of the encouraging preliminary results obtained using such MS animal models.

Hydrogel-based stem cell therapy uses different stem cells and bioactive molecules for wound healing in the treatment of diabetes and chronic burn wounds by accelerating angiogenesis, collagen deposition, and inhibition of inflammatory responses. Artificial vessels have already been used for patients with cardiovascular diseases, but most of them are polymeric, which can cause thrombosis and restenosis. 3D bioprinting combines cells, growth factors, and biomaterials to create a setting in which cells grow and differentiate into native tissue-like structures. The current study aimed to create a model of blood vessels using collagen and hyaluronic acid hydrogel combined with endothelial and muscle progenitor cells derived from amniotic mesenchymal stem cells using 3D bioprinting. A computer-aided design (CAD) software was employed to create the 3D models of a blood vessel model and printed using a 3D bioprinter with two printheads: one with bioink encapsulating endothelial progenitor cells and the second with bioink encapsulating smooth muscle progenitor cells. The blood vessel constructs were characterized morphologically and structurally by Fourier Transform Infrared (FTIR) Spectroscopy, thermogravimetric analysis (TGA), Scanning Electron Microscopy (SEM), immunohistochemistry, water uptake, and enzymatic degradation. Viability, proliferation, oxidative stress, vascular endothelial growth factor (VEGF) and nitric oxide (NO) production were assessed to demonstrate the cytocompatibility of the blood vessel constructs. Our results showed that collagen–hyaluronic acid hydrogels embedded with stem cells can be used for vascular constructs, meeting the desired requirements of biocompatibility and accuracy in reproducing the model created in the CAD software v1.0.