Mesenchymal stem cells and insulin-like growth factor-I gene-enhanced mesenchymal stem cells improve structural aspects of healing in equine flexor digitorum superficialis tendons.
Tendinitis remains a catastrophic injury among athletes. Mesenchymal stem cells (MSCs) have recently been investigated for use in the treatment of tendinitis. Previous work has demonstrated the value of insulin-like growth factor-I (IGF-I) to stimulate cellular proliferation and tendon fiber deposition in the core lesion of tendinitis. This study examined the effects of MSCs, as well as IGF-I gene-enhanced MSCs (AdIGF-MSCs) on tendon healing in vivo. Collagenase-induced bilateral tendinitis lesions were created in equine flexor digitorum superficialis tendons (SDFT). Tendons were treated with 10 x 10(6) MSCs or 10 x 10(6) AdIGF-MSCs. Control limbs were injected with 1 mL of phosphate-buffered saline (PBS). Ultrasound examinations were performed at t = 0, 2, 4, 6, and 8 weeks. Horses were euthanized at 8 weeks and SDFTs were mechanically tested to failure and evaluated for biochemical composition and histologic characteristics. Expression of collagen types I and III, IGF-I, cartilage oligomeric matrix protein (COMP), matrix metalloproteinase-3 (MMP-3), matrix metalloproteinase-13 (MMP-13), and aggrecanase-1 (ADAMTS-4) were similar in MSC and control tendons. Both MSC and AdIGF-MSC injection resulted in significantly improved tendon histological scores. These findings indicate a benefit to the use of MSCs and AdIGF-MSCs for the treatment of tendinitis.
Comparative Orthopaedics Laboratory, Department of Clinical Sciences, C3-187 Veterinary Medical Center, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA.
Lauren V
LV
Schnabel
Maureen E
ME
Lynch
Marjolein C H
MC
van der Meulen
Amy E
AE
Yeager
Matthew A
MA
Kornatowski
Alan J
AJ
Nixon
D051722:ADAM Proteins / Q000378:metabolism; D000071121:ADAMTS4 Protein; D000818:Animals; D001696:Biomechanical Phenomena; D064987:Cell- and Tissue-Based Therapy / Q000379:methods / Q000662:veterinary*; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D015316:Genetic Therapy / Q000379:methods / Q000662:veterinary*; D006023:Glycoproteins / Q000378:metabolism; D006734:Horse Diseases / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D006736:Horses; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D008297:Male; D064235:Matrilin Proteins; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods / Q000662:veterinary*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D011348:Procollagen N-Endopeptidase / Q000378:metabolism; D052256:Tendinopathy / Q000378:metabolism / Q000628:therapy / Q000662:veterinary*; D013710:Tendons / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D014463:Ultrasonography
D024042:Collagen Type I; D024061:Collagen Type III; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D064235:Matrilin Proteins; D007334:Insulin-Like Growth Factor I; D051722:ADAM Proteins; D053509:Matrix Metalloproteinase 13; D011348:Procollagen N-Endopeptidase; D019278:Matrix Metalloproteinase 3; D000071121:ADAMTS4 Protein