eCM (Eur Cell Mater / e Cells & Materials) Not-for-Profit Open Access
Created by Scientists, for Scientists
 ISSN:1473-2262         NLM:100973416 (link)         DOI:10.22203/eCM

2020   Volume No 40 – pages 160-171

Title: Effects of FK506 on the healing of diaphyseal, critical size defects in the rat femur

Authors: RE De la Vega, MJ Coenen, SA Müller, CV Nagelli, NP Quirk, C Lopez de Padilla, CH Evans

Address: Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

E-mail: Evans.christopher at

Abstract: There is much interest in understanding the influence of the immune system on bone healing, including a number of reports suggesting a beneficial effect of FK506 (tacrolimus) in this regard. The influence of FK506 in a rat, femoral, critical size defect was examined using locally implanted, recombinant, human (rh) BMP-2 and adenovirally-transduced, autologous, adipose-derived mesenchymal stromal cells (AD-MSCs) expressing BMP-2. FK506 was delivered systemically using an implanted osmotic pump. Empty defects and those implanted with unmodified AD-MSCs did not heal in the presence or absence of FK506. Defects treated with rhBMP-2 healed with a large callus containing thin cortices and wispy trabeculae; this, too, was unaffected by FK506. A third of defects implanted with adenovirally-transduced AD-MSCs healed, but this improved to 100 % in the presence of FK506. New bone formed in response to BMP-2 synthesised endogenously by the genetically modified cells had a slimmer callus than those healed by rhBMP-2, with improved cortication and advanced reconstitution of marrow. These results suggest that FK506 may have had little effect on the intrinsic biology of bone healing, but improved healing in response to adenovirally-transduced cells by inhibiting immune responses to the first-generation adenovirus used here. Because the genetically modified cells produced bone of higher quality at far lower doses of BMP-2, this approach should be explored in subsequent research.

Key Words: Immunosuppression, bone healing, gene therapy, adenovirus, rat, BMP-2.

Publication date: October 6th 2020

Article download: Pages 160-171 (PDF file)

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