Designer, injectable gels to prevent transplanted Schwann cell loss during spinal cord injury therapy.
Laura M MarquardtVanessa M DoulamesAlice T WangKaren R DubbinRiley A SuharMichael J KratochvilZachary A MedressGiles W PlantSarah C HeilshornPublished in: Science advances (2020)
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.
Keyphrases
- cell cycle arrest
- cell therapy
- cell death
- spinal cord
- single cell
- spinal cord injury
- induced apoptosis
- hyaluronic acid
- combination therapy
- oxidative stress
- drug delivery
- type diabetes
- endoplasmic reticulum stress
- neuropathic pain
- cell proliferation
- blood brain barrier
- subarachnoid hemorrhage
- bone marrow
- ultrasound guided
- weight loss