Successful Nerve Regeneration and Persistence of Donor Cells After a Limited Course of Immunosuppression in Rat Peripheral Nerve Allografts

Abstract

Possible clinical use of a limited course of immunosuppression was supported by this demonstration of long term persistence of donor Schwann cells.

Administration of low-dose FK 506 accelerates histomorphometric regeneration and functional outcomes after allograft nerve repair in a rat model

“…Consequently, axonal regeneration is impeded or limited during the first few weeks following grafting. With time, the allograft might be repopulated by recipient-derived Schwann cells migrating from both proximal and distal stumps, thereby providing support and guidance to axons entering from the proximal stump (Katsube et al, 1998;Udina et al, 2003). Thus, as expected, regeneration and target reinnervation were significantly delayed in our allograft groups.…”

“…The results of studies using FK 506 in models normally showing proficient nerve regeneration indicate that high immunosuppressive dosage for extended periods of time might not be justified (Katsube et al, 1998;Gold et al, 1999;Udina et al, 2004). By finding a minimal dose of FK 506 with maximal neurotrophic effect, objections to the dosage of FK 506 need no longer be raised.…”

“…Significant improvement in nerve regeneration rates could minimize denervation changes and improve longterm functional recovery from nerve injuries: the immunosuppressive drug FK 506 has been shown to have neuroprotective and neurotrophic actions in experimental models, increasing neurite elongation and accelerating the rate of nerve regeneration in vitro and in vivo (Lassner et al, 1989;Gold et al, 1995;Wang et al, 1997;Katsube et al, 1998;Doolabh and Mackinnon, 1999;Jost et al, 2000;Lee et al, 2000;Wang et al, 2002;Udina et al, 2002;Hontanilla et al, 2006). Thus, FK 506 could be useful, even clinically, for enhancing regeneration after surgical repair by improving the rate of axonal growth with allografts.…”

Correlation of three sciatic functional indices with histomorphometric findings in a rat sciatic nerve allograft repair model

“…With time, the allograft might be repopulated by recipient-derived Schwann cells migrating from both proximal and distal stumps, thereby providing support and guidance to axons entering from the proximal stump. 42 Therefore, the neurotrophin receptor p75NTR in Schwann cells is essential for promoting the remyelization of axons. 43 Thus, as expected, regeneration and target reinnervation were significantly delayed in our allograft groups.…”

Histomorphological and functional impacts of postoperative motor training in rats after allograft sciatic nerve transplantation under low‐dose FK 506

“…The immunosuppressive drug FK 506 has been shown to have neuroprotective and neurotrophic actions in experimental models by increasing neurite elongation and accelerating the rate of nerve regeneration in vitro and in vivo. 5,10,12,14,16,18,36,37 Hence, FK 506 could potentially enhance regeneration after surgical nerve repair by improving the rate of axonal growth within transplanted allografts. Positive results in nerve regeneration in animals and humans immunosuppressed by FK 506 were reported in various studies.…”