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Related Experiment Video

Updated: Jul 12, 2026

Transplantation of Human Stem Cell-Derived GABAergic Neurons into the Early Postnatal Mouse Hippocampus to Mitigate Neurodevelopmental Disorders
05:00

Transplantation of Human Stem Cell-Derived GABAergic Neurons into the Early Postnatal Mouse Hippocampus to Mitigate Neurodevelopmental Disorders

Published on: November 11, 2022

Clinical Relevant Immunosuppressive Drugs Differentially Modulate Axonal Outgrowth from Human Stem Cell-Derived

Gunnar H D Poplawski1,2, C Weinholtz1, G Woodruff3

  • 1Department of Neurosciences, University of California - San Diego, La Jolla, CA, USA.

Biorxiv : the Preprint Server for Biology
|July 11, 2026
PubMed
Summary

Choosing the right immunosuppressant is crucial for spinal cord injury (SCI) repair. Cyclosporine A (CsA) hinders nerve regeneration, while FK-506 (tacrolimus) supports it, improving outcomes for neural stem cell transplantation.

Keywords:
FK-506axon growthcyclosporinehiPSChuman NPCsimmunosuppressionneural graftsregenerationspinal cord injury

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Differentiation of a Human Neural Stem Cell Line on Three Dimensional Cultures, Analysis of MicroRNA and Putative Target Genes

Published on: April 12, 2015

Area of Science:

  • Neuroscience
  • Regenerative Medicine
  • Immunology

Background:

  • Spinal cord injury (SCI) repair strategies often involve neural stem cell (NSC) transplantation.
  • Transplanted cells, including induced pluripotent stem cell (iPSC)-derived grafts, typically require immunosuppression to prevent rejection.
  • The impact of immunosuppressive drugs on critical processes like neurite outgrowth and axonal regeneration remains incompletely understood.

Purpose of the Study:

  • To evaluate the effects of nine clinically relevant immunosuppressants on human iPSC-derived neurons and primary human spinal cord NSCs in vitro.
  • To assess the in vivo impact of selected immunosuppressants (CsA and FK-506) on neural progenitor cell graft integration and axon extension in a rodent SCI model.
  • To determine if immunosuppressant choice influences the success of stem cell-based therapies for SCI.

Main Methods:

  • In vitro testing of nine immunosuppressants (FK-506, CsA, rapamycin, belatacept, etanercept, mycophenolate mofetil, cyclophosphamide, prednisone, azathioprine) on human iPSC-derived neurons and NSCs.
  • Quantification of neurite outgrowth using automated high-content imaging at clinically relevant drug concentrations.
  • In vivo assessment of human neural progenitor cell grafts in a rodent SCI model with host treatment using CsA or FK-506, evaluating graft-derived axon extension.

Main Results:

  • Multiple immunosuppressants, notably Cyclosporine A (CsA), mycophenolate mofetil (CellCept), belatacept (Nulojix), and azathioprine (Imuran), significantly reduced neurite outgrowth in vitro.
  • CsA demonstrated the most robust and consistent inhibition of neurite outgrowth across both cell types.
  • FK-506 (tacrolimus) showed no significant impact on neurite extension in vitro. In vivo, CsA treatment led to reduced graft-derived axon extension compared to FK-506 treatment in the SCI model.

Conclusions:

  • The selection of immunosuppressive agents can profoundly impact neural graft integration and axonal regeneration after spinal cord injury.
  • Cyclosporine A (CsA) inhibits critical regenerative processes, whereas FK-506 (tacrolimus) appears to preserve them.
  • Preclinical evaluation of immunosuppressive regimens is essential, and FK-506 may be a preferable choice over CsA for improving outcomes in future stem cell-based therapies for SCI.