1. Investigación

Osteoarthritis (OA) is the most common articular disease in adults and has a current prevalence of 12% in the population over 65 years old. This chronic disease causes damage to articular cartilage and synovial joints, causing pain and leading to a negative impact on patients’ function, decreasing quality of life. There are many limitations regarding OA conventional therapies—pharmacological therapy can cause gastrointestinal, renal, and cardiac adverse effects, and some of them could even be a threat to life. On the other hand, surgical options, such as microfracture, have been used for the last 20 years, but hyaline cartilage has a limited regeneration capacity. In recent years, the interest in new therapies, such as cell-based and cell-free therapies, has been considerably increasing. The purpose of this review is to describe and compare bioregenerative therapies’ efficacy for OA, with particular emphasis on the use of mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP). In OA, these therapies might be an alternative and less invasive treatment than surgery, and a more effective option than conventional therapies.

Traditionally, canine degenerative lumbosacral stenosis (DLS) has been defined as a multifactorial syndrome characterized by lumbosacral pain triggered by the compression of the nerve rootlets of the cauda equina. There is still no consensus on the treatment of this condition, probably because there are a plethora of possible causes. In addition to compression, inflammation is a very important factor in the physiopathology of the disorder. Platelet-rich plasma (PRP) consists of an increased concentration of autologous platelets suspended in a small amount of plasma. Platelets are a source of several growth factors. Growth factors were shown to help in wound healing and biological processes, such as chemotaxis, neovascularization and synthesis of extracellular matrix, and growth factors were used to improve soft tissue healing and bone regeneration. PRP also facilitates the restoration of the structural integrity of the affected anatomy. Fourteen dogs diagnosed with DLS were treated with three epidural injections of PRP on days 0, 15 and 45. All dogs showed clinical improvement 3 months after the initial treatment. Gait was also objectively assessed by means of the use of force platform analysis before and after treatment, showing significant improvement. The results show that PRP may provide a good alternative to other nonsurgical treatments, such as prednisolone epidural injection.

Osteoarthritis (OA) is one of the most significant joint diseases worldwide. There are di erent therapies for OA treatment, and a relatively new strategy is the use of plasma rich in growth factors (PRGF), a platelet rich plasma (PRP) derivative. The objective of this study was to objectively assess the e cacy and duration of the e ect of an intraarticular injection of PRGF and a combination of PRGF + physical therapy. The objective assessment was provided using a force platform. The obtained parameters were peak vertical force (PVF) and vertical impulse (VI). A total of 24 dogs with lameness and pain associated to OA attributable to bilateral hip dysplasia were included in the study. Animals were divided into two study groups and evaluated at baseline and at 30, 90, and 180 days after intraarticular PRGF or PRGF + physical therapy. Significant di erences were observed at every checkpoint with respect to basal time in both groups. However, after 180 days, the PRGF group showed a decrease in PVF and VI with respect to the values obtained at 90 days. However, the PRGF + physical therapy group maintained increased values of both PVF and VI values during the 180-day study period.

The role of platelet-rich plasma (PRP) in promoting the healing of bone fractures has notyet been clearly stated. The aim of this prospective clinical study was to evaluate the effectiveness ofplasma rich in growth factors (PRGF, a PRP derivate) in the treatment of naturally-occurring bonefractures in dogs. With this objective, sixty-five dogs with radius/ulna or tibia/fibula bone fractureswere randomly divided into two groups (PRGF and saline solution (SS) groups) and checked atdays 0, 7, 14, 21, 28, 35, 42, 49, 56, 60, 63, 70, 120, and 180. All the fractures were treated with anexternal skeletal fixation, and pain was controlled with Carprofen. Healing was evaluated by physicalexamination, limb function, radiography, and by a Likert-type owner satisfaction questionnaire.A faster fracture healing was observed in the PRGF group, with statistically significant differenceswith respect to the SS group. Swelling at the fracture site was significantly greater at day 14 and28 in animals injected with PRGF, and more pain on palpation was found in the area at day 28.The injection of PRGF in acute bone fractures accelerates bone healing.

The aim of this study was to evaluate the use of serum type II collagen cleavage epitope and serum hyaluronic acid as biomarkers for treatment monitoring in osteoarthritic dogs. For this purpose, a treatment model based on mesenchymal stem cells derived from adipose tissue combined with plasma rich in growth factors was used. This clinical study included 10 dogs with hip osteoarthritis. Both analytes were measured in serum at baseline, just before applying the treatment, and 1, 3, and 6 months after treatment. These results were compared with those obtained from force plate analysis using the same animals during the same study period. Levels of type II collagen cleavage epitope decreased and those of hyaluronic acid increased with clinical improvement objectively verified via force plate analysis, suggesting these two biomarkers could be effective as indicators of clinical development of joint disease in dogs.

Background: Regenerative medicine using Mesenchymal Stem Cells (MSC) alone or combined with Plasma Rich in Growth Factors (PRGF) is a rapidly growing area of clinical research and is currently also being used to treat osteoarthritis (OA). Force platform analysis has been consistently used to verify and quantify the efficacy of different therapeutic strategies for the treatment of OA in dogs including MSC associated to PRGF, but never with AD-MSC alone. The aim of this study was to use a force platform to measure the efficacy of intraarticular ADMSC administration for limb function improvement in dogs with severe OA. Results: Ten lame dogs with severe hip OA and a control group of 5 sound dogs were used for this study. Results were statistically analyzed to detect a significant increase in peak vertical force (PVF) and vertical impulse (VI) in treated dogs. Mean values of PVF and VI were significantly improved within the first three months post-treatment in the OA group, increasing 9% and 2.5% body weight, respectively, at day 30. After this, the effect seems to decrease reaching initial values. Conclusion: Intraarticular ADMSC therapy objectively improved limb function in dogs with hip OA. The duration of maximal effect was less than 3 months.

Background: Adipose-derived mesenchymal stem cell (ADMSC) therapy in regenerative medicine is a rapidly growing area of research and is currently also being used to treat osteoarthritis (OA). Force platform analysis has been consistently used to verify the efficacy of different therapeutic strategies for the treatment of OA in dogs, but never with AD-MSC. The aim of this study was to use a force platform to measure the efficacy of intraarticular ADMSC administration for limb function improvement in dogs with severe OA. Results: Eight lame dogs with severe hip OA and a control group of 5 sound dogs were used for this study. Results were statistically analyzed to detect a significant increase in peak vertical force (PVF) and vertical impulse (VI) in treated dogs. Mean values of PVF and VI were significantly improved after treatment of the OA groups, reaching 53.02% and 14.84% of body weight, respectively, at day 180, compared with only 43.56% and 12.16% at day 0. Conclusion: This study objectively demonstrated that intraarticular ADMSC therapy resulted in reduced lameness due to OA.

The overall increase of chronic degenerative diseases associated with ageing makes wound care a tremendous socioeconomic burden. Thus, there is a growing need to develop novel wound healing therapies to improve cutaneous wound healing. The use of regenerative therapies is becoming increasingly popular due to the low-invasive procedures needed to apply them. Platelet-rich plasma (PRP) is gaining interest due to its potential to stimulate and accelerate the wound healing process. The cytokines and growth factors forming PRP play a crucial role in the healing process. This article reviews the emerging field of skin wound regenerative therapies with particular emphasis on PRP and the role of growth factors in the wound healing process.

Osteoarthritis (OA) is a major cause of disability in elderly population around the world. More than one-third of people over 65 years old shows either clinical or radiological evidence of OA. There is no effective treatment for this degenerative disease, due to the limited capacity for spontaneous cartilage regeneration. Regarding the use of regenerative therapies, it has been reported that one option to restore degenerated cartilage are adipose-derived mesenchymal stem cells (ASCs). The purpose of this review is to describe and compare the efficacy of ASCs versus other therapies in OA. Methods: Recent studies have shown that ASCs exert paracrine effects protecting against degenerative changes in chondrocytes. According to the above, we have carried out a review of the literature using a combination of osteoarthritis, stem cells, and regenerative therapies as keywords. Results: Conventional pharmacological therapies for OA treatment are considered before the surgical option, however, they do not stop the progression of the disease. Moreover, total joint replacement is not recommended for patients under 55 years, and high tibia osteotomy (HTO) is a viable solution to address lower limb malalignment with concomitant OA, but some complications have been described. In recent years, the use of mesenchymal stem cells (MSCs) as a treatment strategy for OA is increasing considerably, thanks to their capacity to improve symptoms together with joint functionality and, therefore, the patients’ quality of life. Conclusions: ASC therapy has a positive effect on patients with OA, although there is limited evidence and little long-term follow-up.

Low invasiveness is the main goal of modern surgery. The use of platelet-rich plasma (PRP) is known to be effective in a variety of applications, such as oral, maxillofacial, orthopedic, dermatologic and cosmetic surgeries. However, a potential ergogenic and carcinogenic effect of PRP derivatives by means of the insulin-like growth factor-1 (IGF-1) pathway has been suggested. Because of this notion, the purpose of this study is to assess the effect of a commercially available PRP-derivative intramuscular injection in the lumbar muscular tissue (local effect) and to determine the IGF-1 blood concentration (systemic effect) on healthy beagle dogs. Local effect was evaluated by computed tomography (CT) scan and echography, and systemic effect was calculated by blood testing on days 0, 14, 28, 42 and 56. No statistically significant changes were observed; thus, PRGF could be considered safe when using therapeutic doses.