Introduction: Stroke is a leading cause of adult disability, with a limited process of neural repair. Induced pluripotent glial progenitor cells (iPS-GEPs) have not been previously studied in cortical stroke but may be a promising therapeutic intervention due to their ability to differentiate into immature astrocytes. We have previously described a hydrogel suspension made up of a hyaluronic backbone with nanoparticles embedded with VEGF (hCv), engineered to serve as a tissue scaffold to promote progenitor cell survival and differentiation (1-4).

Methods: We combined the novel use of human iPS-GEP cells with an injectable hydrogel (hCv) in a murine model of cortical stroke. We transplanted iPS-GEP cells embedded in a hydrogel to adult mice at a subacute time point (7 days) after a photothrombotic stroke. Additional groups included iPS-GEP cells without hydrogel, iPS-neural progenitor cells (iPS-NPC), and iPS-NPC with injectable hydrogel (hCv). Exploratory forelimb use and foot fault behavior tasks were used to assess motor recovery at baseline, 1 week (subacute), 1 month, 2 month, and 3 month (chronic) time points.

Results: All mice displayed a significant motor deficit at 1 week with a gradual improvement to baseline levels over 3 months. While transplantation with hydrogel did result in a relative behavioral improvement at 1 month, at a 3 month time point there was no difference in between groups that had received hydrogel and those that had not. The transplantation of neural progenitor cells versus glial enriched progenitor cells had no differential effect on motor recovery after stroke. Cellular transplantation did provide a significant behavior improvement versus hydrogel alone.

Conclusions: The results from this study are important in further characterizing the role of glial and neural progenitor cells in motor recovery after cortical stroke and highlighting the potential role for a structural hydrogel in this process.

Patient Care: Cortical stroke is a prevalent illness that results in long-term disability. There are currently no therapies available in the subacute and chronic time points for these patients. The development of induced pluripotent stem cell lines that result in behavioral improvement would be a critical finding that could be translated into human clinical trials and a viable therapy for these patients.

Learning Objectives: By the conclusion of this session, participants should be able to: 1) Describe the process of endogenous neural repair after stroke 2) Discuss the differentiation, migration, and behavioral recovery after stem cell implantation in cortical stroke 3) Identify the novel uses of glial progenitor cells and hydrogels in stroke

References: 1. Moshayedi P, Nih LR, Llorente IL, Berg AR, Cinkornpumin J, Lowry WE, et al. Systematic optimization of an engineered hydrogel allows for selective control of human neural stem cell survival and differentiation after transplantation in the stroke brain. Biomaterials [Internet]. 2016;105:145–155. Available from: http://dx.doi.org/10.1016/j.biomaterials.2016.07.028 2. Lam J, Lowry WE, Carmichael ST, Segura T. Delivery of iPS-NPCs to the Stroke Cavity within a Hyaluronic Acid Matrix Promotes the Differentiation of Transplanted Cells. Adv Funct Mater [Internet]. 2014;24:7053–7062. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26213530 3. Nih LR, Carmichael ST, Segura T. Hydrogels for brain repair after stroke: An emerging treatment option. Curr. Opin. Biotechnol. [Internet]. 2016;40:155–163. Available from: http://dx.doi.org/10.1016/j.copbio.2016.04.021 4. Moshayedi P, Carmichael ST. Hyaluronan, neural stem cells and tissue reconstruction after acute ischemic stroke. Biomatter [Internet]. 2013;3:e23863. Available from: http://www.tandfonline.com/doi/abs/10.4161/biom.23863