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Cortical Transplantation of Brain‐Mimetic Glycosaminoglycan Scaffolds and Neural Progenitor Cells Promotes Vascular Regeneration and Functional Recovery after Ischemic Stroke in Mice
Author(s) -
McCrary Myles R.,
Jesson Kaleena,
Wei Zheng Z.,
Logun Meghan,
Lenear Christopher,
Tan Stephen,
Gu Xiaohuan,
Jiang Michael Q.,
Karumbaiah Lohitash,
Yu Shan Ping,
Wei Ling
Publication year - 2020
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201900285
Subject(s) - transplantation , progenitor cell , neural stem cell , angiogenesis , neuroscience , stroke (engine) , medicine , regeneration (biology) , induced pluripotent stem cell , regenerative medicine , basic fibroblast growth factor , stem cell , biology , microbiology and biotechnology , growth factor , cancer research , surgery , embryonic stem cell , receptor , mechanical engineering , engineering , biochemistry , gene
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.