Long-Term Effects of Fibrin Conduit with Human Mesenchymal Stem Cells and Immunosuppression after Peripheral Nerve Repair in a Xenogenic Model

Aleksandra M McGrath; Maria Brohlin; Rebecca Wiberg; Paul J Kingham; Lev N Novikov; Mikael Wiberg; Liudmila N Novikova

doi:10.1177/2155179018760327

Long-Term Effects of Fibrin Conduit with Human Mesenchymal Stem Cells and Immunosuppression after Peripheral Nerve Repair in a Xenogenic Model

Cell Med. 2018 May 31:10:2155179018760327. doi: 10.1177/2155179018760327. eCollection 2018.

Authors

Aleksandra M McGrath^{1

2}, Maria Brohlin^{1

3}, Rebecca Wiberg^{1

2}, Paul J Kingham¹, Lev N Novikov¹, Mikael Wiberg^{1

2}, Liudmila N Novikova¹

Affiliations

¹ Department of Integrative Medical Biology, Section for Anatomy, Umeå University, Umeå, Sweden.
² Department of Surgical and Perioperative Science, Section for Hand and Plastic Surgery, Norrland's University Hospital, Umeå, Sweden.
³ Department of Clinical Microbiology, Infection and Immunology, Umeå University, Umeå, Sweden.

Abstract

Introduction: Previously we showed that a fibrin glue conduit with human mesenchymal stem cells (hMSCs) and cyclosporine A (CsA) enhanced early nerve regeneration. In this study long term effects of this conduit are investigated.

Methods: In a rat model, the sciatic nerve was repaired with fibrin conduit containing fibrin matrix, fibrin conduit containing fibrin matrix with CsA treatment and fibrin conduit containing fibrin matrix with hMSCs and CsA treatment, and also with nerve graft as control.

Results: At 12 weeks 34% of motoneurons of the control group regenerated axons through the fibrin conduit. CsA treatment alone or with hMSCs resulted in axon regeneration of 67% and 64% motoneurons respectively. The gastrocnemius muscle weight was reduced in the conduit with fibrin matrix. The treatment with CsA or CsA with hMSCs induced recovery of the muscle weight and size of fast type fibers towards the levels of the nerve graft group.

Discussion: The transplantation of hMSCs for peripheral nerve injury should be optimized to demonstrate their beneficial effects. The CsA may have its own effect on nerve regeneration.

Keywords: gastrocnemius muscle; human mesenchymal stem cells; immunosuppression; peripheral nerve injury; spinal motoneurons.