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IGF-1 stimulates axon regeneration in composite tissue allotransplantation
Sami Tuffaha, Timothy W. Ng, Megan Quigley, Komli Atsina, Gerald Brandacher and W.P. Andrew Lee
2010-04-05
Presenter: Sami Tuffaha
Affidavit:
Director Name:
Author Category: Resident/Fellow
Presentation Category: Basic Science Research
Abstract Category: Hand
BACKGROUND:
Composite Tissue Allotransplantation of the upper extremity is now a clinical reality. Although incomplete MHC matching remains a challenge, clinicians must also address functional outcomes in the limb graft. Nerve axons, unfortunately, regenerate at a maximum rate of 2 mm/ day. Due to the length of the human arm, irreversible muscular atrophy may occur before nerves reach their appropriate endplates.
IGF-1 may provide a solution. It is a natural peptide hormone that stimulates cellular growth and prevents apoptosis in almost all body tissues, including nerve.
METHODS:
A completely MHC mismatched, orthotopic hindlimb transplant using Brown Norway (BN) to Lewis rats was performed. Five control animals were created, and treated daily with intraperitoneal (IP) FK506 1 mg/kg/day to maintain the graft. Five experimental animals were treated with IP FK506 (1 mg/kg/day) and subcutaneous IGF-1 (1 mg/kg/day, 4x physiological concentration). Both FK506 and IGF-1 were administered for 21 days post-op.
On the 22nd day post-op, animals the BN graft sciatic nerve was harvested, preserved, and then thin cross-sections were produced and stained. Estimates of nerve density and total axon count were obtained using histomorphometry software.
RESULTS:
IGF-1 treated animals had a threefold increase in nerve density; IGF-1 nerves had ~3000 fibers/mm^2 compared to 1000 fibers/mm^2 controls. Additionally, there was a fourfold increase in overall fiber count; ~4000 fibers in IGF-1 vs. ~1000 in controls. Differences were statistically significant on student's T test.
SUMMARY:
Our study is the first to demonstrate the ability of IGF-1 to increase axonal regeneration in CTA.
