Page 931 - Adams and Stashak's Lameness in Horses, 7th Edition

Principles of Therapy for Lameness 897

be heterogeneous with regard to cell type. A small con- groups as compared with the saline‐treated controls.
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trolled study using adipose‐derived cells in a collagenase Studies now need to be performed comparing the effi-
VetBooks.ir of crimp pattern. Another study reported a return to derived MSCs.
model of tendon injury reported some benefit in terms
cacy of TDPC with bone marrow‐derived and adipose‐
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athleticism in 14 out of 16 horses with SDF tendonitis
with no comment on reinjury rate. Up until now, no
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head‐to‐head comparison studies of adipose‐derived to BLOOD‐DERIVED BIOLOGICS: PLATELET‐RICH
bone marrow‐derived MSCs have been performed in PLASMA, AUTOLOGOUS CONDITIONED SERUM,
clinical cases of naturally occurring disease. AUTOLOGOUS PROTEIN SOLUTION, AND BONE
The culture‐expanded bone marrow‐derived MSC MARROW ASPIRATE
therapy involves aspirating bone marrow from the ster-
num or tuber coxae, transferring to a laboratory for cul- Platelet‐rich plasma (PRP) has been used for treat-
ture and expansion, and then implanting the cell ment of soft tissue injuries and bone healing and has
population (approximately 10–50 × 10 ) under ultra- been investigated for regeneration of bone, cartilage,
6
sound guidance. Continued investigation of tissue tendon, and ligament. The reason behind the use of PRP
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uptake of these cells has shown retention of the stem comes from the knowledge that growth factors are
cells within the lesion for up to 9 weeks when injected released from platelet α‐granules including platelet‐
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intralesionally. This technique has been widely used in derived growth factor (PDGF), transforming growth
the United States, the United Kingdom, Europe, and factor‐β (TGF‐β), fibroblastic growth factor (FGF), vas-
Australia. cular endothelial growth factor (VEGF), insulin‐like
Currently, long‐term follow‐up is encouraging. In a growth factor‐I (IGF‐I), and epidermal growth factor
2008 study, over 168 racehorses undergoing this regi- (EGF). Many animal models have demonstrated positive
men were shown to have an 18% reinjury rate. This is effects of these growth factors, both alone and in con-
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in contrast to a 56% reinjury rate for horses receiving cert with each, in enhancing cellular migration and pro-
no intralesional therapy. Two smaller‐scale studies one liferation, angiogenesis and matrix deposition in tendon
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in research horses and one in 11 racehorses also and wound healing and repair. 1,3,38
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reported improved tendon repair. In a more recent study Current studies report beneficial effects of PRP on
by Godwin et al., 141 racehorses with overstrain inju- equine ligament and tendon both in vitro and in
ries of the SDFT were treated intralesionally with bone vivo. 30,42,44 In vitro studies support the belief that PRP
marrow‐derived MSC and followed with repeat ultra- supplies high levels of growth factors and the presence
sonography. A re‐injury rate of 27.4% was reported for of these growth factors results in higher type I collagen
this population after a 2‐year period. No adverse and cartilage oligomeric matrix protein (COMP) and
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effects were reported in these studies other than ultra- reduced levels of inflammatory mediators such as
sonographic evidence of needle tracks. matrix metalloproteinases (MMP) 3 and 13. A recent in
The efficacy of administering stem cells via regional vivo study reported improved repair of the SDFT when
limb perfusion (RLP) has also been evaluated via tech- core lesions were induced mechanically. When lesions
5
netium‐99m‐labeled cells, which has shown a homing that were injected with PRP were compared with lesions
effect to the region of injury. Additionally, the efficacy injected with saline, tendons had better mechanical
10
of intra‐arterial administration of MSCs has recently characteristics as well as higher collagen, glycosamino-
been investigated. Technetium‐labeled MSCs injected glycan, and cellularity. These findings correlate with the
into the median artery via ultrasound guidance were in vitro effects reported. A more recent randomized
shown to perfuse into the entire distal limb via scinti- controlled study was performed using intralesional
graphic imaging. Longer‐term evaluation of tissue injection of either PRP or saline in 20 horses with natu-
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uptake when administered via RLP or intra‐arterially rally occurring tendinopathies. At 12‐month follow‐up,
has yet to be investigated. 80% of the PRP‐treated horses had reached their previ-
In addition to autologous stem cell usage, in which a ous or a higher level of performance as compared with
sample is harvested from the patient, cultured, and rein- 50% in the control. However, after 24 months only
jected intralesionally, investigation of the safety of allo- 60% of the treated horses and 40% of the control were
genic stem cell use has been reported. In a retrospective still used at this level. Additionally, in a retrospective
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study of 164 horses receiving bone marrow‐derived review of 127 National Hunt racehorses, intralesional
stem cells from a single donor, 10/230 injection sites PRP was not superior to other treatments in the studied
were reported to have adverse reactions which is not population, which included controlled exercise and bar
dissimilar to allogeneic administration. Adverse reac- firing. 45
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tions were defined as pain, swelling, heat, or lameness PRP is also commonly used in conjunction with
associated with the injection site. Seven of these reac- extracorporeal shockwave therapy (ESWT) (see section
tions were in soft tissue injections. 43 on topical/local). An in vitro study showed that concen-
Tendon‐derived progenitor cells (TDPC) have also trations of TGF‐β and PDGF‐ββ were significantly
1
been investigated in recent years as an alternative to increased when PRP was exposed to ESWT; however
bone marrow or stem cell therapies. Cells are harvested this model has not been validated in vivo. 40
from a donor tendon site, such as the lateral digital Autologous conditioned serum (ACS) has become
extensor tendon, and then cultured for intralesional popular for its anecdotal anti‐inflammatory effects and
injection. In a recent study model using collagenase‐ rapid improvement in lameness. ACS is similar to PRP in
induced tendon lesions, improved tensile strength and its rapid processing and ease of acquisition. Whole blood
fiber alignment were shown in the TDPC‐treated is processed via exposure to glass beads, which stimulates