Biomedical Engineering Reference
In-Depth Information
NP tissue [ 129 ]. Thus, the use of a healthy alternative human NP cell source
in conjunction with an appropriate scaffold may be the most beneficial approach
to NP TE.
9 Animal Models of IDD
Animal models make possible the study of etiological mechanisms associated with
IDD while allowing for the investigation of the efficacy of potential therapeutic
approaches. Numerous animal models have been investigated that reflect the
biochemical, radiological, and histological changes observed within degenerating
human IVDs. Although these models provide important clues towards developing
treatment strategies, the selection of model and interpretation of results must be
approached cautiously due to intrinsic differences between animal species and
humans (e.g., IVD size and aspect ratio, anatomical variation in adjacent spinal
structures, variations in disc cell populations and metabolism, biochemical compo-
sition, biomechanics) [ 130 , 131 ].
Animal models of IDD can be broadly classified into two categories: naturally
occurring and experimentally induced. Macaques, beagles, and sand rats are a few
examples of animals that appear to naturally develop evidence of IDD over the
course of their lives [ 132 - 134 ]. One of the most widely investigated animal models
of induced degeneration includes lumbar disc puncture models. Masuda et al. found
that using 16G and 18G needles to penetrate through the AF into the NP of
New Zealand white rabbits resulted in a mild and reproducible model of disc
degeneration, as indicated by reductions in disc height, histological staining for
proteoglycan, and MRI signal intensity [ 135 ]. Degenerative changes were observed
as early as 2 weeks post-puncture with progression of degeneration through the
8 week study. Similar results were attained by Sobajima et al. who observed a
progressive loss in NP area and MRI signal intensity as early as 3 weeks, which
progressed over the 24-week study [ 136 ]. Degenerative findings included a
decrease in the number of notochordal cells, fluctuating numbers of NP cells,
formation of a fibrocartilagenous NP, osteophyte formation, and end-plate sclerosis
[ 136 ]. Annular stab models using scalpels have also been performed in Sprague-
Dawley rats, sheep, and pigs resulting in similar outcomes [ 137 , 138 ].
Other forms of induced degeneration include axial overloading of the disc to
stimulate degeneration [ 139 , 140 ], intradiscal injection of an apoptotic (campto-
thecin) [ 141 ], and chemonucleolytic agents such as chondroitinase ABC [ 142 ].
Zhou et al. showed that intradiscal injection of bromodeoxyuridine (BrdU), a
known mutagen that incorporates into DNA in place of thymidine, created a cellular
senescence/aging model of degeneration in sheep IVDs [ 143 ].
Choice of the ideal animal model to test tissue engineered strategies has to
balance cost and relevance. The naturally occurring macaque model would be a
primary choice; however, the costs may be prohibitive, especially for the academic
arena. Other large animals such as goats and sheep may also pose cost limitations
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