Expandable Sendai-Virus-Reprogrammed Human iPSC-Neuronal Precursors: In Vivo Post-Grafting Safety Characterization in Rats and Adult Pig

Cell Transplant. 2023 Jan-Dec:32:9636897221107009. doi: 10.1177/09636897221107009.

Abstract

One of the challenges in clinical translation of cell-replacement therapies is the definition of optimal cell generation and storage/recovery protocols which would permit a rapid preparation of cell-treatment products for patient administration. Besides, the availability of injection devices that are simple to use is critical for potential future dissemination of any spinally targeted cell-replacement therapy into general medical practice. Here, we compared the engraftment properties of established human-induced pluripotent stem cells (hiPSCs)-derived neural precursor cell (NPCs) line once cells were harvested fresh from the cell culture or previously frozen and then grafted into striata or spinal cord of the immunodeficient rat. A newly developed human spinal injection device equipped with a spinal cord pulsation-cancelation magnetic needle was also tested for its safety in an adult immunosuppressed pig. Previously frozen NPCs showed similar post-grafting survival and differentiation profile as was seen for freshly harvested cells. Testing of human injection device showed acceptable safety with no detectable surgical procedure or spinal NPCs injection-related side effects.

Keywords: cryopreservation; human induced pluripotent stem cells (hiPSCs); human injection device; immunosuppressed adult pig; neural precursor cells (NPCs); spinal cord.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Brain
  • Cell Differentiation / physiology
  • Cellular Reprogramming* / genetics
  • Cellular Reprogramming* / physiology
  • Genetic Vectors / genetics
  • Graft Survival / physiology
  • Humans
  • Induced Pluripotent Stem Cells* / physiology
  • Induced Pluripotent Stem Cells* / transplantation
  • Injections, Spinal* / adverse effects
  • Injections, Spinal* / instrumentation
  • Injections, Spinal* / methods
  • Neural Stem Cells* / physiology
  • Neural Stem Cells* / transplantation
  • Rats
  • Sendai virus
  • Specimen Handling / methods
  • Spinal Cord
  • Stem Cell Transplantation* / adverse effects
  • Stem Cell Transplantation* / instrumentation
  • Stem Cell Transplantation* / methods
  • Swine
  • Tissue and Organ Harvesting / methods
  • Treatment Outcome