Induced Pluripotent Stem Cell (iPS) Derived Schwann Cells to Enhance Functional Recovery Following Nerve Injury and Limb Allotransplantation.

B. Kern,¹ K. Sarhane,² Z. Ibrahim,² B. Mukherjee-Clavin,³ J. Budihardjo,² C. Cashman,³ K. Krick,⁴ S. Schneeberger,¹ W. Lee,² H.-Q. Mao,⁴ G. Lee,³ G. Brandacher.²

¹Operative Medicine, Innsbruck Medical University, Innsbruck, Austria
²Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
³Neurology and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD
⁴Materials Science and Engineering, Johns Hopkins University School of Medicine, Baltimore, MD

Meeting: 2017 American Transplant Congress

Abstract number: D5

Keywords: Growth factors, Outcome, Stem cells, Tissue-specific

Session Information

Session Name: Poster Session D: Cellular & Bone Marrow Transplantation Session II

Session Type: Poster Session

Date: Tuesday, May 2, 2017

Session Time: 6:00pm-7:00pm

Presentation Time: 6:00pm-7:00pm

Location: Hall D1

Background Stem cell therapies have provided new aspects for functional recovery. A novel cell-based approach utilizing human induced Pluripotent Stem Cell-derived Schwann Cells (iPSC-SCs) supported by the effect of nerve growth factors was investigated to improve functional recovery in a rodent model.

Materials & Methods Experiments were conducted in a chronic denervation and rat hindlimb model. Human iPSC-SCs were generated through dual SMAD inhibition and isolated by FACS. For Schwann cell differentiation, CD49d+ cells were isolated. Growth factor delivery systems were constructed using fibrin gel containing growth factor GDNF with or without chondroitinase.

Results Figure 1 shows derivation of Schwann Cells Precursors (SCPs); cells assume a typical SCs long fusiform bipolar morphology (A), stain positive to S100 (B), and were successfully transfected with a green fluorescent protein (GFP) adenovector (C). Histomorphometry demonstrated a significant increase in the number of regenerating myelinated axons in the GDNF+chondroitinase group as compared to GDNF, chondroitinase, and negative control groups. Animals treated with iPSC delivery demonstrated significantly greater axonal diameters and myelin thickness. EMG functional testing and Catwalk gait analysis did not show any significant difference, neither at 5 nor at 12 weeks, although there was a positive trend.

Conclusion: Growth factor delivery vehicles and chondritinase result in higher axonal counts. Human iPS cells result in greater axonal diamters and myelin thickness. Further studies are needed to demonstrate functional benefits of cellular therapies for nerve regeneration.

CITATION INFORMATION: Kern B, Sarhane K, Ibrahim Z, Mukherjee-Clavin B, Budihardjo J, Cashman C, Krick K, Schneeberger S, Lee W, Mao H.-Q, Lee G, Brandacher G. Induced Pluripotent Stem Cell (iPS) Derived Schwann Cells to Enhance Functional Recovery Following Nerve Injury and Limb Allotransplantation. Am J Transplant. 2017;17 (suppl 3).

To cite this abstract in AMA style:

Kern B, Sarhane K, Ibrahim Z, Mukherjee-Clavin B, Budihardjo J, Cashman C, Krick K, Schneeberger S, Lee W, Mao H-Q, Lee G, Brandacher G. Induced Pluripotent Stem Cell (iPS) Derived Schwann Cells to Enhance Functional Recovery Following Nerve Injury and Limb Allotransplantation. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/induced-pluripotent-stem-cell-ips-derived-schwann-cells-to-enhance-functional-recovery-following-nerve-injury-and-limb-allotransplantation/. Accessed November 21, 2024.

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