Effects of different subcutaneous sites on heterotopic autotransplantation of canine ovarian tissue.

Ovarian tissue transplantation makes it possible to restore fertility; however, the success of this technique depends on the transplant region used. Therefore, this study aimed to evaluate the effect of two subcutaneous regions on canine ovarian transplantation, pinna (Pi) and neck (Ne), for 7 and 15 days. Ovaries collected by ovariosalpingohysterectomy were fragmented using a punch device. Fresh fragments were fixed, and the others were immediately grafted onto the animal itself in the Pi and Ne regions for 7 and 15 days. Recovered fragments were evaluated for histology (morphology, development and stromal density), picrosirius (collagen fibers), and immunohistochemistry (fibrosis and cell proliferation). The results showed that follicular normality rates were lower in Pi-7 (78%) vs. control (90%) and Pi-15 (86%), similar in Ne-7 (92%) and superior in Ne-15 (97%) compared to the control, with the effect of the region Ne (94%) superior (P < 0.05) to Pi (82%). Stromal density reduced in both regions vs. control but was similar within 15 days. Fragments from both regions showed higher fibronectin labeling and deposition of type I and lower type III collagen fibers (P < 0.05) vs. control. Proliferation rates in Ne-7 were higher (P < 0.05) than in control, and Pi-15 was higher (P < 0.05) than Ne-15. In conclusion, the pinna may be a region with greater potential than the neck after a 15-day autotransplantation of canine ovarian tissue.

Reconstruction of a partial esophageal defect using tunica vaginalis and buccal mucosa autograft: an experimental study in mongrel dogs.

In veterinary clinics, esophageal reconstruction is essential in many clinical situations. In this study, two autografts, the tunica vaginalis (TV) and the buccal mucosa (BM), were proposed to reconstruct a semi-circumferential cervical esophageal defect in dogs. This study aimed to verify whether these two grafts could successfully patch esophageal defects. Twelve male mongrel dogs were divided into two groups. Following cervical esophagoplasty, the defective area was patched with either a TV or a BM graft. Comprehensive clinical, serum biochemical, and histological analyses were performed to evaluate the two grafts. Throughout the study (120 days), the dogs survived the procedure well with minor complications. The lumen of the patched areas was covered with mucosa, with slight scar retraction. Compared with that of the natural esophagus, the average relative luminal diameter was not significantly decreased. Importantly, the measured cortisol and inflammatory marker levels returned to the preoperative levels after 14 days. Although histological examination revealed that both grafts repaired the esophageal defect with complete re-epithelialization, the BM graft showed a histological structure similar to that of the natural esophagus. Both grafts effectively repaired the esophageal defect with minor complications; therefore, both are recommended as promising low-cost clinical alternatives for cervical esophagoplasty in dogs.

Field Safety Experience With an Autologous Cancer Vaccine in 41 Horses: A Retrospective Study (2019-2021).

Autologous cancer vaccines (ACV) are an emerging option for adjuvant cancer treatment in veterinary medicine. With this form of active immunotherapy, the patient's tumor cells are processed ex vivo and returned to the patient with the goal of stimulating an immune response to unique, patient-specific antigens. The case accession database at Torigen was queried to identify horses that underwent biopsy or surgical resection of their primary tumor and received at least one subcutaneous dose of an adjuvanted whole-cell autologous cancer vaccine. The records were then reviewed for any reported adverse events (AE). Forty-one horses met the inclusion criteria and received 252 doses of Torigen's ACV (ACV-T). There were seven AEs reported in four horses, which were associated with 1.6% of the administered doses of the ACV-T. Of the reported AE, all were characterized as mild. The ACV-T appears to be well tolerated by horses, and may be useful as a treatment option for owners who are concerned about AEs that can occur with other types of adjuvant cancer therapy. Additional studies are warranted to evaluate the efficacy of this ACV in horses with solid tumors.

Use of autologous products for the treatment of joint and soft tissue disease in horses: A systematic review.

BACKGROUND: Soft tissue injuries and joint disease are the predominate causes of lameness in the equine athlete and these pathologies carry a guarded prognosis for a return to previous performance. Recently the use of autologous products has become more widespread as a treatment in equine sports medicine. However, the efficacy of these products is yet to be fully established. OBJECTIVE: To evaluate the current published evidence base regarding the efficacy of autologous products in soft tissue injuries and joint disease. METHODS: A systematic review of English articles using MEDLINE, EMBASE and Web of Science databases from 1980 to 2017. The search strategy identified 1594 papers for review. RESULTS: Fifty-eight papers were included in this review, 28 of which were randomised controlled trials. Significant benefit was reported under several parameters, most notably in the use of autologous chondrocytes in artificially induced cartilage defects on histology. One paper documented a significant clinical response under lameness examination. CONCLUSION: The current literature shows that the treatment of soft tissue injury and cartilage disease with autologous products is safe and that the use of some products can give significant benefit on some outcome measures. True clinical significance is yet to be demonstrated with any product.

Autologous lamellar keratoplasty for the treatment of feline corneal sequestrum: A retrospective study of 35 eyes (2012-2020).

OBJECTIVE: To evaluate the use of autologous lamellar keratoplasty for the treatment of feline corneal sequestrum (FCS). PROCEDURE: The medical records of cats diagnosed with FCS that underwent autologous lamellar keratoplasty between 2012 and 2020 with a minimum of 2 months of follow-up were reviewed. After keratectomy of FCS, a button adjacent to the corneal limbus was harvested on the same eye and sutured to the recipient bed. A nictitating membrane flap was left in place until the first recheck except for one patient. Postoperative treatment with topical and systemic antibiotics and systemic nonsteroidal anti-inflammatory medications was prescribed. Follow-up examinations were carried out 2 weeks, 1 month and 2 months post-operatively and consisted of a complete ophthalmic examination. RESULTS: A total of 35 cats (35 eyes) were included. The median follow-up time was 3.2 months (range, 2-59 months). Brachycephalic cats were overrepresented (85.7%). The mean graft size was 6.5 mm (range, 6-9 mm). Minor complications consisting of melting and partial integration of the graft occurred in 2/35 eyes (5.7%). Recurrence was observed in 1/35 eyes (2.9%) and was managed by a superficial keratectomy. A good visual outcome was achieved in all eyes, and a faint or mild corneal opacification occurred in 15/35 (42.9%). CONCLUSIONS: Autologous lamellar keratoplasty is an effective treatment for FCS, providing good tectonic support to the affected cornea and resulting in good visual and cosmetic outcomes. These results should be verified in future prospective studies that include a larger number of cases and longer-term follow-up.

Heterotopic autotransplantation of equine ovarian tissue using intramuscular versus subvulvar grafting sites: Preliminary results.

Ovarian tissue transplantation (OTT) is a technique well established and successfully applied in humans using mainly orthotopic or heterotopic transplantation sites. In livestock, OTT is still in its infancy and, therefore, different aspects of the technique, including the efficiency of different heterotopic OTT sites as well as the potential effect of age (i.e., young vs. old mares) in the ovarian graft quality, need to be investigated. The present study investigated the efficacy of the intramuscular (IM) or the novel subvulvar mucosa (SV) heterotopic autotransplantation sites to maintain the survivability of the grafts for 3 and 7 days post-OTT. Ovarian biopsy fragments were obtained in vivo and distributed to the following treatments: Fresh control group (ovarian fragments immediately fixed), SV-3, IM-3, SV-7, and IM-7. During and after graft harvesting, the macroscopic characteristics of the grafts (i.e., adherence, morphology, and bleeding) were scored, and the percentages of morphologically normal and developing preantral follicles as well as the follicular and stromal cell densities of the grafts were evaluated. The results were that similar (P > 0.05) macroscopic scores were observed between both transplantation sites 7 days post-OTT, with positive correlations (P < 0.01) found among adherence, morphology, and bleeding of the grafts. A lower (P < 0.05) percentage of morphologically normal follicles was found 7 days post-OTT in the SV site (82%) compared with the Fresh control group (99%) and IM site (95%); however, the percentages of developing follicles were similar (P > 0.05) between both transplantation sites 7 days post-OTT (30-43%). Although similar (P > 0.05) follicular densities were found in both transplantation sites in young and old mares at 3 and 7 days post-OTT, large individual variation in the follicular depletion rate was observed regardless of transplantation site. The Fresh control group and SV-7 treatments had higher (P < 0.05) stromal cell densities in young and old mares compared with both IM-7 treatments. When comparing transplant sites between young and old mares, the follicular density in old mares and the stromal cell density in young mares were greater (P < 0.05) in the SV than in the IM site. In conclusion, even though the transplantation sites differentially affected some end points, overall comparable findings of the OTT technique using both heterotopic autotransplantation sites (i.e., IM and SV) for equine ovarian tissue were observed.

Biomechanical analysis of accessory tendon graft augmentation for primary gastrocnemius tendon reconstruction in dogs.

OBJECTIVE: To evaluate the effect of accessory tendon graft (ATG) augmentation as an adjunct to a core locking-loop (LL) and epitendinous suture (ES) repair in a gastrocnemius tendon (GT) model. STUDY DESIGN: Randomized, ex vivo, biomechanical. POPULATION: Twenty-two canine GT musculotendinous constructs. METHODS: GT repair constructs were randomly divided into two groups (n = 10/group). After transection, paired GT were repaired with LL + ES alone or with concurrent ATG augmentation. Yield, peak and failure loads, tensile loads required to create 1 and 3 mm gapping, and failure modes were evaluated. Four GT were used as intact controls for validation of testing methodology. ATG constructs were compared to LL + ES and control specimens. RESULTS: Yield (p < .0001), peak (p = .0001) and failure loads (p = .0003) were greater when ATG was used for repair. Greater force was required to cause 1 mm (p = .0001) and 3 mm (p = .0002) gap formation in the ATG group, however, the frequency of gap formation did not differ between groups. All repaired constructs failed exclusively by suture pull-through. CONCLUSION: Autologous ATG augmentation as an adjunct to primary GT repair increased yield, peak and failure forces by approximately 1.6×, 1.9×, 1.8× respectively and required 2.1× greater force to cause 1 and 3 mm formation respectively compared to LL + ES repairs alone. CLINICAL SIGNIFICANCE: ATG augmentation should be considered as an autologous method to support and strengthen the primary GT repair. These results justify studies to determine the effect of ATG on clinical function following graft harvest in dogs.

Efficacy of autologous bone marrow mononuclear cell transplantation in dogs with chronic spinal cord injury.

Background: Spinal cord injury (SCI) is relatively common in dogs and is a devastating condition involving loss of sensory neurons and motor neurons. However, the main clinical protocol for the management of SCI is surgery to decompress and stabilize the vertebra. Cell transplantation therapy is a very promising strategy for the treatment of chronic SCI, but extensive preclinical and clinical research work remains. Aim: The aim of this study is to confirm the effect of bone marrow-derived mononuclear cell (BM-MNC) transplantation for chronic SCI in dogs. Methods: We tested the treatment efficiency of chronic SCI in 12 dogs using BM-MNC transplantation. Neurological evaluation used the Texas Spinal Cord Injury Scale (TSCIS). Concurrently, we characterized the transplanted cells by evaluation using quantitative real-time polymerase chain reaction, flow cytometry, and enzyme-linked immunosorbent assay. Result: All dogs had a pre-transplantation TSCIS score of 0. Two animals did not show any improvement in their final TSCIS scores. The remaining 10 dogs (83.4%) achieved improvement in the final TSCIS scores. Five of them (41.7%) regained ambulatory function with a TSCIS score greater than 10. We determined that canine BM-MNCs expressed hepatocyte growth factor (HGF) mRNA at higher levels than other cytokines, with significant increases in HGF levels in cerebrospinal fluid within 48 hours after autologous BM-MNC transplantation into the subarachnoid space of the spinal dura matter in dogs. Conclusions: BM-MNC transplantation may be effective for at least some cases of chronic SCI.

Biomechanical evaluation of an autologous flexor digitorum lateralis graft to augment the surgical repair of gastrocnemius tendon laceration in a canine ex vivo model.

OBJECTIVE: To evaluate the effect of an autologous flexor digitorum lateralis (FDL) graft to augment a three-loop pulley (3LP) core repair in a canine cadaveric gastrocnemius tendon (GT) laceration model. STUDY DESIGN: Ex vivo, biomechanical study. SAMPLE POPULATION: Twenty-six canine cadaveric hind limbs. METHODS: Tendons were divided into two groups (n = 13). After sharp transection, paired GT were repaired with 3LP or 3LP + FDL tendon augmentation. Yield, peak and failure loads, tensile loads required to create 1 and 3-mm gapping, and failure modes were analyzed. Significance was set at P < .05. RESULTS: Yield and failure force (mean ± SD) for 3LP + FDL were 134.9 ± 44.1 N and 205.4 ± 46.4 N, respectively, which were greater than for 3LP alone (67.9 ± 12.2 N and 91.8 ± 9.9 N, respectively, P < .0001). No constructs (0%) formed 1 or 3-mm gaps in the 3LP + FDL graft group compared with 84% and 39% for 3LP, respectively (P < .0001). Failure modes were different between groups (P < .001), with 85% of 3LP + FDL constructs failing by tissue rupture at the myotendinous junction, distant to the repair site. CONCLUSION: Addition of an autologous FDL graft to a core 3LP tendon repair increased yield, peak, and failure forces by twofold, 2.3-fold, and 2.2-fold, respectively, compared with core 3LP alone while preventing the occurrence of gap formation. CLINICAL SIGNIFICANCE: Use of FDL tendon augmentation for GT laceration may increase repair site strength and resist gap formation better than 3LP core suture use alone. Additional studies are required in vivo to determine the effect of FDL graft augmentation on clinical function.

Evaluation of a Single Intra-Articular Injection of Autologous Adipose Tissue for the Treatment of Osteoarthritis: A Prospective Clinical Study in Dogs.

OBJECTIVE: The aim of this study was to investigate the safety, feasibility and clinical efficacy of a single intra-articular injection of autologous and purified micro-fragmented adipose tissue for the treatment of osteoarthritis (OA) in dogs. STUDY DESIGN: Twenty-one client-owned dogs with radiographically confirmed OA were recruited into this prospective study. Lameness and discomfort were evaluated by physical examination at day 0 and then 14, 30, 60 and 180 days after injection. Kinetic data and temporospatial parameters were obtained using a pressure-sensing walkway. Peak vertical force, vertical impulse and percentages of body weight distribution were determined. Owner perception data regarding their own dog's physical activity were also collected using the Canine Brief Pain Inventory. RESULTS: Radiographic scores for OA from days 0 to 180 were similar, except in two dogs. No major side effects were noted after injection. Lameness and Canine Brief Pain Inventory scores were significantly lower at all time points compared with day 0. Post-injection results demonstrated gradual improvement of kinetic data up to day 180 compared with pre-treatment values: vertical impulse (>2.25%), peak vertical force (>5.32%) and percentages of body weight distribution (>3.6%). In dogs with elbow OA, gait analysis values significantly increased at all time points compared with day 0. CONCLUSION: Regenerative autologous adipose tissue injection therapy is a promising alternative to traditional analgesics treatment in patients with OA, associated with significant reductions in pain and lameness, delayed disease progression and improved quality of life.

Treatment of a femoral septic nonunion in a dog with interlocking nail stabilization associated to corticospongious bone autograft and greater omentum flap: case report / Tratamento de não união séptica femoral em cão com estabilização com haste intramedular bloqueada associada a autoenxerto de osso corticoesponjoso e retalho do omento maior: relato de caso

Chronic septic bone nonunion requires a well-designed therapeutic planning, demanding a multimodal treatment to achieve bone consolidation and elimination of infection. A successful case of an association of the major omentum flap with surgical stabilization with an interlocking nail for treatment of a femoral septic nonunion in dog is reported. The patient had partial functional return of the limb 30 days after surgery, negative bacterial culture with radiographic signs of bone healing and total functional return of the limb at 90th days after the surgical procedure.(AU)

Não uniões ósseas associadas à osteomielite crônica necessitam de um planejamento terapêutico muito bem realizado, demandando tratamento multimodal para conseguir atingir a consolidação óssea e eliminar a infecção. Relatou-se um caso de sucesso do uso da associação de retalho do omento maior com estabilização cirúrgica com haste intramedular bloqueada para tratamento de uma não união séptica de fêmur em cão. O paciente apresentou retorno funcional parcial do membro com 30 dias após a cirurgia, cultura bacteriana estéril com sinais radiográficos de consolidação óssea e retorno funcional total do membro aos 90 dias de pós-operatório.(AU)

Efficacy of frozen autograft treated with liquid nitrogen in limb-sparing surgery in feline scapular osteosarcoma: A case report.

In recent years, a novel technique of limb preservation has been used in human medicine that involves frozen autograft treated with liquid nitrogen. In this case, frozen autograft treatment along with shoulder joint reconstruction was performed in an 11-year-old cat with osteosarcoma of the distal scapula. Surgical site infection, shoulder dislocation, local recurrence, and pulmonary metastases were not reported for 24 months after surgery. Moreover, the patient was able to bear weight on the operated limb after 2 months of surgery, and excellent limb function without lameness was demonstrated after 15 months. The frozen autograft technique is advantageous because it is inexpensive, simple, and retains its initial strength after treatment, and could be a novel treatment in feline osteosarcoma.

Pyroptosis is involved in cryopreservation and auto-transplantation of mouse ovarian tissues and pyroptosis inhibition improves ovarian graft function.

The aim of this study was to investigate the role of pyroptosis in the cryopreservation and transplantation of mouse ovarian tissues; the effects of pyroptosis inhibitior on the ovarian graft function were also explored. ICR (institute of cancer research) mice were randomly divided into control group and experimental groups (n = 10 per group). The experimental groups included fresh graft group (autograft), cryopreserved graft group (cryopreservation + autograft), and pyroptosis inhibition group (cryopreservation + autograft + pyroptosis inhibitor). At the third day after auto-transplantation, caspase-1 and NLRP3 protein expression in grafts were assessed by Western blot; in the meantime, serum concentration of IL-1ß was examined by ELISA. After 28 days of auto-transplantation, estradiol concentrations and follicular densities of grafts were evaluated. The caspase-1 and NLRP3 protein expression in grafts from all the experimental groups were significantly higher than that from control group respectively; moreover, there was a significant increase in serum concentrations of IL-1ß in all experimental groups compared with control group. The concentration of estradiol and follicular densities of grafts in pyroptosis inhibition group were significantly higher than that in cryopreserved graft group. Pyroptosis is involved in cryopreservation and auto-transplantation of mouse ovarian tissues, and pyroptosis inhibition can improve the ovarian graft function.

Hübner's eyelid reconstruction using a free tarsomarginal autograft in eight dogs. A retrospective study.

OBJECTIVE: The aim of our work was to study the potential of tarsomarginal grafting technique, in canine. ANIMAL STUDIED: All dogs included in this study had tumors of the upper or lower eyelid. Furthermore, resection of the tumor necessitated excision of the eyelid margin comprising 1/4 and 2/3. PROCEDURE: Harvesting of the graft with the length of half the length of the tumor, including its free margins was performed via a full-thickness incision on the ipsilateral healthy eyelid. The cutaneous layer and all of the muscle fibers of the transplant were meticulously removed except a 3 mm strip along the free lid margin. A full-thickness tumor excision was then performed. The graft was sutured at the level of the defect to be reconstructed. A sliding H flap was generated. The resulting nourishing myocutaneous flap was then sutured along the free margin of the tarso-conjunctivo-marginal graft. The lateral edges of the advancement flap were sutured to the edges of the receiving sites. RESULTS: The average size of the reconstructed area was 17.8 mm. The resulting stretched lid fissure length after surgery was shortened over 7 to 11 mm. This technique for grafting was used to reconstruct an eyelid that had lost tissue measuring between 1/4 and 2/3 of its length. The few complications that were encountered were mainly the occurrence of keratitis or suture dehiscence. CONCLUSIONS: This tarsomarginal grafting technique has yielded encouraging results in dogs. This technique can fill large lid defects with a physiologic lid margin but is shortening the stretched lid fissure length.

Production of functional sperm by subcutaneous auto-grafting of immature testes in rainbow trout.

Sexually mature individuals are indispensable for breeding programs. Salmonids require a long period before reaching sexual maturity, so we aimed to shorten the period required to obtain functional sperm by grafting immature testicular fragments into mature recipients, which we predicted would allow the grafted testicular fragments to skip the long pre-pubertal period. First, we demonstrated successful subcutaneous auto-grafting of testicular fragments in rainbow trout. Unilateral testectomy was performed, and the isolated immature testicular fragment was auto-grafted into the subcutaneous space along the back of recipient fish. The grafted testicular fragments developed synchronously with the recipients' testis remaining in its body cavity, and both eventually produced functional sperm. Next, immature testicular fragments were auto-grafted into the subcutaneous space of sexually mature males. We achieved this, without immune rejection, by isolating and cryopreserving testes from immature fish, and rearing these unilaterally testectomized fish until sexual maturity. The cryopreserved testes were then auto-grafted into the original, now spermiating fish. The grated immature testicular fragments differentiated and produced functional sperm within 5 months after grafting. By combining this grafting method with a technique to avoid immune rejection, we expect to develop a practical method for producing sperm in a shorter period in salmonids.

Proof of concept of a new autologous skin substitute for the treatment of deep wounds in dogs.

Autologous skin grafts are effective for the repair of large skin wounds, but the availability of large amounts of skin is often limited. Through bioengineering, several autologous skin substitutes have been developed for use in human clinical practice. However, few skin substitutes are available for use in animals. The aim of this study was to develop and assess an engineered autologous skin substitute for the treatment of deep wounds in veterinary medicine. Canine keratinocytes and fibroblasts were isolated after double enzyme digestion from 8mm punch biopsies from four healthy Beagle dogs. Skin substitutes were constructed on a fibrin-based matrix and grafting capacity was assessed by xenografting in six athymic mice. Bioengineered autologous skin was assessed clinically in two dogs with large deep skin wounds. The canine skin construct was ready for use within 12-14days after the initial biopsy specimens were obtained. Grafting capacity in this model was confirmed by successful grafting of the construct in athymic mice. In both dogs, grafts were established and permanent epithelialisation occurred. Histological studies confirmed successful grafting. This full thickness skin substitute developed for the management of large skin defects in dogs appears to be a safe and useful tool for clinical veterinary practice. Further studies are needed to validate its efficacy for the treatment of deep wounds.

Transferência de autoenxerto osteocondral para tratamento de osteocondrite dissecante em côndilo femoral de cão / Osteochondral autograft transfer for treatment of osteochondritis dissecans of the femoral condyle in a dog

Na osteocondrite dissecante (OCD), a articulação do ombro é mais comumente afetada, mas o joelho é ocasionalmente lesionado, o que, muitas vezes, passa desapercebido. O tratamento cirúrgico precoce é indicado para remover cartilagem solta, aliviar a dor e minimizar a artrose. Benefícios putativos da transferência de autoenxerto osteocondral em relação às técnicas convencionais incluem a reconstrução exata do contorno subcondral e articular, recobrimento da superfície com cartilagem hialina e criação de uma barreira imediata entre o líquido sinovial e o osso subcondral. O objetivo deste trabalho é relatar a técnica de transferência de autoenxerto osteocondral para o tratamento da osteocondrite do côndilo femoral. Um cão da raça Bull Terrier foi tratado cirurgicamente por meio da técnica de transferência de autoenxerto osteocondral, após ter sido diagnosticado com OCD do côndilo femoral, apresentando melhora clínica significativa e completa recuperação aos 30 dias de pós-operatório.(AU)

In osteochondritis dissecans (OCD), the shoulder joint is most commonly involved, but the stifle is occasionally involved and often goes unnoticed. Early surgical treatment is indicated to remove loose cartilage and minimize osteoartrosis. Putative benefits of Osteochondral Autograft Transfer (OAT) over conventional techniques include accurate reconstruction of subchondral and articular contour, resurfacing with hyaline or hyaline-like cartilage, and creation of an immediate barrier between synovial fluid and subchondral bone. The purpose of this work is to report the technique of OATs for the treatment of osteochondritis of the femoral condyle. A canine attended the Laboratory of Comparative Orthopedics and Traumatology USP-FMVZ underwent surgery after being diagnosed with OCD of the femoral condyle, with significant clinical improvement at 30 days postoperatively.(AU)

Tissue blood flow to a pedicled jejunal autograft in the dog: A pilot study.

OBJECTIVE: To determine the viability of a pedicled jejunal autograft after ligation of up to 3 jejunal arteries. STUDY DESIGN: Prospective crossover study. ANIMALS: Three adult dogs. METHODS: Dogs were instrumented for measurement of hemodynamic parameters. Two segments of jejunum with 4 arcadial vessels were isolated from the abdomen in each dog. An individual ligature was secured around the 4th, 3rd, and 2nd jejunal artery. The 1st jejunal artery was maintained to serve as the sole blood supply to the pedicled segment of jejunum. Colored microspheres were used to evaluate the effect of each ligation on tissue blood flow. RESULTS: Mean arterial blood pressure (P = .709) and heart rate (P = .905) did not differ between ligation groups. Tissue blood flow to a pedicled segment of jejunum was unchanged after ligation of 3 jejunal arteries. CONCLUSION: Tissue blood flow of an isolated jejunal segment maintained in normal position remains unaffected, when supplied by a single jejunal artery, after ligation of up to 3 concurrent jejunal arteries.

Autologous Bone Marrow-Derived Mesenchymal Stem Cells Modulate Molecular Markers of Inflammation in Dogs with Cruciate Ligament Rupture.

Mid-substance rupture of the canine cranial cruciate ligament rupture (CR) and associated stifle osteoarthritis (OA) is an important veterinary health problem. CR causes stifle joint instability and contralateral CR often develops. The dog is an important model for human anterior cruciate ligament (ACL) rupture, where rupture of graft repair or the contralateral ACL is also common. This suggests that both genetic and environmental factors may increase ligament rupture risk. We investigated use of bone marrow-derived mesenchymal stem cells (BM-MSCs) to reduce systemic and stifle joint inflammatory responses in dogs with CR. Twelve dogs with unilateral CR and contralateral stable partial CR were enrolled prospectively. BM-MSCs were collected during surgical treatment of the unstable CR stifle and culture-expanded. BM-MSCs were subsequently injected at a dose of 2x106 BM-MSCs/kg intravenously and 5x106 BM-MSCs by intra-articular injection of the partial CR stifle. Blood (entry, 4 and 8 weeks) and stifle synovial fluid (entry and 8 weeks) were obtained after BM-MSC injection. No adverse events after BM-MSC treatment were detected. Circulating CD8+ T lymphocytes were lower after BM-MSC injection. Serum C-reactive protein (CRP) was decreased at 4 weeks and serum CXCL8 was increased at 8 weeks. Synovial CRP in the complete CR stifle was decreased at 8 weeks. Synovial IFNγ was also lower in both stifles after BM-MSC injection. Synovial/serum CRP ratio at diagnosis in the partial CR stifle was significantly correlated with development of a second CR. Systemic and intra-articular injection of autologous BM-MSCs in dogs with partial CR suppresses systemic and stifle joint inflammation, including CRP concentrations. Intra-articular injection of autologous BM-MSCs had profound effects on the correlation and conditional dependencies of cytokines using causal networks. Such treatment effects could ameliorate risk of a second CR by modifying the stifle joint inflammatory response associated with cranial cruciate ligament matrix degeneration or damage.