title: Distribution and persistence of technetium-99 hexamethyl propylene amine oxime-labelled bone marrow-derived mesenchymal stem cells in experimentally induced tendon lesions after intratendinous injection and regional perfusion of the equine distal limb.
abstract: BACKGROUND
  Intralesional (i.l.) injection is currently the most commonly used technique for stem cell therapy in equine tendon injury. A comparison of different techniques of injection of mesenchymal stem cells for the treatment of tendon lesions is required.
  
  
  OBJECTIVE
  We hypothesised that vascular perfusion of the equine distal limb with mesenchymal stem cells (MSCs) would result in preferential distribution of MSCs to acute tendon injuries.
  
  
  METHODS
  In vivo experimental study.
  
  
  METHODS
  Lesions were surgically induced in forelimb superficial digital flexor tendons of 8 horses. Three or 10 days after lesion induction, technetium-99 hexamethyl propylene amine oxime-labelled MSCs were injected via i.v. or intra-arterial (i.a.) regional limb perfusion (RLP) at the level of the distal antebrachium and compared to i.l. injection. Mesenchymal stem cell persistence and distribution within the forelimb and tendon lesions was assessed with scintigraphy for 24 h.
  
  
  RESULTS
  Lesion uptake was higher with i.l. injection than with RLP, but MSC persistence decreased similarly over time in all 3 techniques. Intra-arterial RLP resulted in a better distribution of MSCs and a higher uptake at the lesion site than i.v. RLP. Limbs perfused i.a. on Day 10 showed greater accumulation of MSCs in the lesion than limbs perfused on Day 3. Arterial thrombosis occurred in 50% of the i.v. RLP limbs and in 100% of the i.a. RLP limbs, which led to clinical complications in one horse.
  
  
  CONCLUSIONS
  Compared with i.l. injection, RLP results in lower uptake but similar persistence of MSCs at the site of tendon lesions. A time dependent accumulation of MSCs was identified with i.a. RLP. The i.a. RLP appears more advantageous than the i.v. RLP in terms of distribution and uptake. However, the described i.a. technique produced arterial thrombosis and thus cannot currently be recommended for clinical use.
authors.affiliation: Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California, USA.
authors.forename: A
authors.initials: A
authors.lastname: Sole
authors.forename: M
authors.initials: M
authors.lastname: Spriet
authors.forename: K A
authors.initials: KA
authors.lastname: Padgett
authors.forename: B
authors.initials: B
authors.lastname: Vaughan
authors.forename: L D
authors.initials: LD
authors.lastname: Galuppo
authors.forename: D L
authors.initials: DL
authors.lastname: Borjesson
authors.forename: E R
authors.initials: ER
authors.lastname: Wisner
authors.forename: M A
authors.initials: MA
authors.lastname: Vidal
mesh_terms: D000818:Animals; D005260:Female; D005552:Forelimb; D006734:Horse Diseases / Q000000981:diagnostic imaging / Q000628:therapy*; D006736:Horses; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000662:veterinary*; D011877:Radionuclide Imaging / Q000662:veterinary; D019690:Technetium Tc 99m Exametazime / Q000494:pharmacology*; D013708:Tendon Injuries / Q000000981:diagnostic imaging / Q000628:therapy*; D014463:Ultrasonography
chemical_list: D019690:Technetium Tc 99m Exametazime
keywords: HMPAO; experimental injury; horse; mesenchymal stem cell; regional limb perfusion; scintigraphy; superficial digital flexor tendon