Regenerative Medicine for Tendon/Ligament Injuries: De Novo Equine Tendon/Ligament Neotissue Generation and Application
Doctor of Philosophy (PhD)
Veterinary Clinical Sciences
Tendon and ligament injuries are debilitating conditions across species. Poor regenerative capacities of these tissues limit restoration of original functions. The first study evaluated the effect of cellular administration on tendon/ligament injuries in horses using meta-analysis. The cellular administration was effective in restoring ultrasonographic echogenicity and increasing vascularity during early phase of healing. Additionally, it improved microstructural organization of healed tissue in terms of cellularity and fiber alignment. However, the study did not support its use for increasing rate of return to performance, expression/deposition of tendon-specific genes/proteins, or mechanical properties.
The findings led to the second study that engineered implantable de novo tendon neotissue using equine adipose-derived multipotent stromal cells and collagen type I. Neotendon cultured in tenogenic medium using custom-designed bioreactor contained highly proliferative tenoblast-like cells that matured and progressively deposited abundant extracellular matrix over 21-day culture period, forming embryonic tendon-like tissue, whereas neotissue cultured in stromal medium contained non-proliferative sparse spherical cells loosely attached to template throughout the culture period.
The neotendon was evaluated for its biocompatibility and therapeutic potential in the third study using immunocompetent and immunocompromised rat bilateral calcaneal tendon elongation model. Neotendon was demonstrated to be biocompatible in immunocompetent rats, and pre-implantation differentiation was essential to maintain phenotype, as neotissue cultured in stromal medium formed amorphous tissue. And the role immune cells play on aberrant tissue formation of non-differentiated neotissue was suggested to be critical.
The fourth study investigated the therapeutic effects of neotendon in surgically-induced non-terminal equine accessory ligament of deep digital flexor tendon injury model. The model rendered minimum morbidity with impaired limb use until 9 weeks post-injury. Lesion recapitulated naturally-occurring injuries ultrasonographically and clinically. Implanted neotendon led to formation of pre-mature tendon tissue that integrated with native tissue within lesion, demonstrating robust healing potential.
Collectively, the work in this dissertation systematically analyzed the effects of cellular therapies to treat tendon/ligament injuries and identified the limitations. Following development of novel neotendon represents a potential breakthrough to overcome these limitations. Further evaluation of neotendon on its therapeutic efficacies is likely to contribute to improved healing of tendon and ligament in equine and other species.
Taguchi, Takashi, "Regenerative Medicine for Tendon/Ligament Injuries: De Novo Equine Tendon/Ligament Neotissue Generation and Application" (2023). LSU Doctoral Dissertations. 6138.
Lopez, Mandi J
Available for download on Thursday, April 25, 2030
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