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  • Designer, injectable gels to prevent transplanted Schwann cell loss during spinal cord injury therapy. Science advances Marquardt, L. M., Doulames, V. M., Wang, A. T., Dubbin, K., Suhar, R. A., Kratochvil, M. J., Medress, Z. A., Plant, G. W., Heilshorn, S. C. 2020; 6 (14): eaaz1039

    Abstract

    Transplantation of patient-derived Schwann cells is a promising regenerative medicine therapy for spinal cord injuries; however, therapeutic efficacy is compromised by inefficient cell delivery. We present a materials-based strategy that addresses three common causes of transplanted cell death: (i) membrane damage during injection, (ii) cell leakage from the injection site, and (iii) apoptosis due to loss of endogenous matrix. Using protein engineering and peptide-based assembly, we designed injectable hydrogels with modular cell-adhesive and mechanical properties. In a cervical contusion model, our hydrogel matrix resulted in a greater than 700% improvement in successful Schwann cell transplantation. The combination therapy of cells and gel significantly improved the spatial distribution of transplanted cells within the endogenous tissue. A reduction in cystic cavitation and neuronal loss were also observed with substantial increases in forelimb strength and coordination. Using an injectable hydrogel matrix, therefore, can markedly improve the outcomes of cellular transplantation therapies.

    View details for DOI 10.1126/sciadv.aaz1039

    View details for PubMedID 32270042

  • Stem cell therapies for acute spinal cord injury in humans: a review NEUROSURGICAL FOCUS Jin, M. C., Medress, Z. A., Azad, T. D., Doulames, V. M., Veeravagu, A. 2019; 46 (3): E10

    Abstract

    Recent advances in stem cell biology present significant opportunities to advance clinical applications of stem cell-based therapies for spinal cord injury (SCI). In this review, the authors critically analyze the basic science and translational evidence that supports the use of various stem cell sources, including induced pluripotent stem cells, oligodendrocyte precursor cells, and mesenchymal stem cells. They subsequently explore recent advances in stem cell biology and discuss ongoing clinical translation efforts, including combinatorial strategies utilizing scaffolds, biogels, and growth factors to augment stem cell survival, function, and engraftment. Finally, the authors discuss the evolution of stem cell therapies for SCI by providing an overview of completed (n = 18) and ongoing (n = 9) clinical trials.

    View details for DOI 10.3171/2018.12.FOCUS18602

    View details for Web of Science ID 000460130200010

    View details for PubMedID 30835679

  • Induced Pluripotent Stem Cell Therapies for Cervical Spinal Cord Injury. International journal of molecular sciences Doulames, V. M., Plant, G. W. 2016; 17 (4)

    Abstract

    Cervical-level injuries account for the majority of presented spinal cord injuries (SCIs) to date. Despite the increase in survival rates due to emergency medicine improvements, overall quality of life remains poor, with patients facing variable deficits in respiratory and motor function. Therapies aiming to ameliorate symptoms and restore function, even partially, are urgently needed. Current therapeutic avenues in SCI seek to increase regenerative capacities through trophic and immunomodulatory factors, provide scaffolding to bridge the lesion site and promote regeneration of native axons, and to replace SCI-lost neurons and glia via intraspinal transplantation. Induced pluripotent stem cells (iPSCs) are a clinically viable means to accomplish this; they have no major ethical barriers, sources can be patient-matched and collected using non-invasive methods. In addition, the patient's own cells can be used to establish a starter population capable of producing multiple cell types. To date, there is only a limited pool of research examining iPSC-derived transplants in SCI-even less research that is specific to cervical injury. The purpose of the review herein is to explore both preclinical and clinical recent advances in iPSC therapies with a detailed focus on cervical spinal cord injury.

    View details for DOI 10.3390/ijms17040530

    View details for PubMedID 27070598

    View details for PubMedCentralID PMC4848986

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