Designer, injectable gels to prevent transplanted Schwann cell loss during spinal cord injury therapy

Sci Adv. 2020 Apr 1;6(14):eaaz1039. doi: 10.1126/sciadv.aaz1039. eCollection 2020 Apr.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biochemical Phenomena
  • Biomechanical Phenomena
  • Cell Membrane
  • Cell Survival / drug effects
  • Disease Models, Animal
  • Female
  • Fluorescent Antibody Technique
  • Hydrogels* / chemistry
  • Neuroprotective Agents / administration & dosage*
  • Rats
  • Recombinant Proteins / administration & dosage*
  • Schwann Cells / drug effects
  • Schwann Cells / metabolism
  • Schwann Cells / transplantation*
  • Spinal Cord Injuries / etiology
  • Spinal Cord Injuries / rehabilitation
  • Spinal Cord Injuries / therapy*

Substances

  • Hydrogels
  • Neuroprotective Agents
  • Recombinant Proteins