Cortical Transplantation of Brain-Mimetic Glycosaminoglycan Scaffolds and Neural Progenitor Cells Promotes Vascular Regeneration and Functional Recovery after Ischemic Stroke in Mice

• Authors: Myles R McCrary, Emory University; Kaleena Jesson, Emory University; Zheng Zachory Wei, Emory University; Meghan Logun, University of Georgia; Christopher Lenear, University of Georgia; Stephen Tan, Emory University; Xiaohuan Gu, Emory University; Michael Q Jiang, Emory University; Lohitash Karumbaiah, University of Georgia; Shan Ping Yu, Emory University; Ling Wei, Emory University
• Journal Title: ADVANCED HEALTHCARE MATERIALS
• Volume: Volume 9, Number 5
• Publisher: WILEY | 2020-01-24, Pages e1900285-e1900285
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1002/adhm.201900285
• Subjects: Biology, Neuroscience; Health Sciences, Rehabilitation and Therapy
• Keywords: Science & Technology; Technology; Engineering, Biomedical; Nanoscience & Nanotechnology; Materials Science, Biomaterials; Engineering; Science & Technology - Other Topics; Materials Science; hydrogels; neural progenitor cells; neural regeneration; stroke; CHONDROITIN SULFATE GLYCOSAMINOGLYCANS; STEM-CELLS; INCREASES REGENERATION; THERAPEUTIC BENEFITS; INTRANASAL DELIVERY; CEREBRAL-ISCHEMIA; HEPARAN-SULFATE; HYDROGEL; DIFFERENTIATION; PROLIFERATION

Abstract

Stroke causes significant mortality and morbidity. Currently, there are no treatments which can regenerate brain tissue lost to infarction. Neural progenitor cells (NPCs) are at the forefront of preclinical studies for regenerative stroke therapies. NPCs can differentiate into and replace neurons and promote endogenous recovery mechanisms such as angiogenesis via trophic factor production and release. The stroke core is hypothetically the ideal location for replacement of neural tissue since it is in situ and develops into a potential space where injections may be targeted with minimal compression of healthy peri-infarct tissue. However, the compromised perfusion and tissue degradation following ischemia create an inhospitable environment resistant to cellular therapy. Overcoming these limitations is critical to advancing cellular therapy. In this work, the therapeutic potential of mouse-induced pluripotent stem cell derived NPCs is tested encapsulated in a basic fibroblast growth factor (bFGF) binding chondroitin sulfate-A (CS-A) hydrogel transplanted into the infarct core in a mouse sensorimotor cortex mini-stroke model. It is shown that CS-A encapsulation significantly improves vascular remodeling, cortical blood flow, and sensorimotor behavioral outcomes after stroke. It is found these improvements are negated by blocking bFGF, suggesting that the sustained trophic signaling endowed by the CS-A hydrogel combined with NPC transplantation can promote tissue repair.