Modern Concepts in Regenerative Therapy for Ischemic Stroke: From Stem Cells for Promoting Angiogenesis to 3D-Bioprinted Scaffolds Customized via Carotid Shear Stress Analysis

Abstract

Ischemic stroke is associated with a tremendous economic and societal burden, and only a few therapies are currently available for the treatment of this devastating disease. The main therapeutic approaches used nowadays for the treatment of ischemic brain injury aim to achieve reperfusion, neuroprotection and neurorecovery. Therapeutic angiogenesis also seems to represent a promising tool to improve the prognosis of cerebral ischemia. This review aims to present the modern concepts and the current status of regenerative therapy for ischemic stroke and discuss the main results of major clinical trials addressing the effectiveness of stem cell therapy for achieving neuroregeneration in ischemic stroke. At the same time, as a glimpse into the future, this article describes modern concepts for stroke prevention, such as the implantation of bioprinted scaffolds seeded with stem cells, whose 3D geometry is customized according to carotid shear stress.

Advances in Tissue Engineering and Innovative Fabrication Techniques for 3-D-Structures: Translational Applications in Neurodegenerative Diseases

“…Limitations with these approaches included the non-homogeneity of the scaffold and the need for vascularization [ 222 , 224 , 225 ]. Another scaffolding approach used for the treatment of AIS is 3-D bioprinting [ 228 ]. In the case of AIS, biomaterials can favor cellular integration and reduce the immune response [ 228 , 229 , 230 ].…”

“…Another scaffolding approach used for the treatment of AIS is 3-D bioprinting [ 228 ]. In the case of AIS, biomaterials can favor cellular integration and reduce the immune response [ 228 , 229 , 230 ].…”

“…There is a need to develop a strategy to correctly implant hydrogels, and also in this case, as reported for ALS, an MRI-guided approach could be adopted [ 225 , 246 ]. It is very interesting to report that in the case of AIS, bio-scaffolds could also serve as a preventive tool, especially in cases where atherosclerotic plaques are already present and represent a strong risk factor for AIS insurgence [ 228 ]. Although no trials have yet been done, the combination of computational fluid dynamics based on patients’ imaging and scaffolds with a patient-specific 3-D geometry could allow first the testing and then the implantation of devices able to correct the arterial flow [ 228 ].…”

Monocyte Transmodulation: The Next Novel Therapeutic Approach in Overcoming Ischemic Stroke?

“…However, few patients with ischemic stroke onset can be served timely with thrombolytic treatment, which mainly focuses on the rapid reperfusion, from the acute phase of occlusion. Therefore, to overcome the limitations, strategies ultimately promoting neurorecovery have been investigated (178). As a part of these therapeutic strategies, bioprinting, an emerging modern technology mixing cells related with tissue regeneration, such as stem cells, with biomaterials that are designed with high precision in order to obtain high compatibility with host tissues, has been developed (179,180).…”

Circular RNA circPHC3 Promotes Cell Death and Apoptosis in Human BMECs After Oxygen Glucose Deprivation via miR-455-5p/TRAF3 Axis in vitro

“…But only a few patients could benefit from timely initiation of reoxygenation/reperfusion. 27 Thus, we focus on in vitro OGD model in this study. Besides, reoxygenation after OGD will be investigate in our future work.…”