Intra-osseous plasma rich in growth factors enhances cartilage and subchondral bone regeneration in rabbits with acute full thickness chondral defects: Histological assessment.

Background: Intra-articular (IA) combined with intra-osseous (IO) infiltration of plasma rich in growth factors (PRGF) have been proposed as an alternative approach to treat patients with severe osteoarthritis (OA) and subchondral bone damage. The aim of the study is to evaluate the efficacy of IO injections of PRGF to treat acute full depth chondral lesion in a rabbit model by using two histological validated scales (OARSI and ICRS II). Methodology: A total of 40 rabbits were included in the study. A full depth chondral defect was created in the medial femoral condyle and then animals were divided into 2 groups depending on the IO treatment injected on surgery day: control group (IA injection of PRGF and IO injection of saline) and treatment group (IA combined with IO injection of PRGF). Animals were euthanized 56 and 84 days after surgery and the condyles were processed for posterior histological evaluation. Results: Better scores were obtained in treatment group in both scoring systems at 56- and 84-days follow-up than in control group. Additionally, longer-term histological benefits have been obtained in the treatment group. Conclusions: The results suggests that IO infiltration of PRGF enhances cartilage and subchondral bone healing more than the IA-only PRGF infiltration and provides longer-lasting beneficial effects.

Multilineage-Differentiating Stress-Enduring Cells (Muse Cells): The Future of Human and Veterinary Regenerative Medicine.

In recent years, several studies have been conducted on Muse cells mainly due to their pluripotency, high tolerance to stress, self-renewal capacity, ability to repair DNA damage and not being tumoral. Additionally, since these stem cells can be isolated from different tissues in the adult organism, obtaining them is not considered an ethical problem, providing an advantage over embryonic stem cells. Regarding their therapeutic potential, few studies have reported clinical applications in the treatment of different diseases, such as aortic aneurysm and chondral injuries in the mouse or acute myocardial infarction in the swine, rabbit, sheep and in humans. This review aims to describe the characterization of Muse cells, show their biological characteristics, explain the differences between Muse cells and mesenchymal stem cells, and present their contribution to the treatment of some diseases.

Corrigendum: Evaluation of a Standardized Protocol for Plasma Rich in Growth Factors Obtention in Cats: A Prospective Study.

[This corrects the article DOI: 10.3389/fvets.2022.866547.].

Evaluation of a Standardized Protocol for Plasma Rich in Growth Factors Obtention in Cats: A Prospective Study.

Introduction: Platelet-rich plasma (PRP) is an autologous plasma with platelet (PLT) concentration above that of whole blood (WB). PLTs contain growth factors (GFs) that promote tissular repair. Objectives: To determine and compare the concentrations of PLT, red blood cells (RBC) and white blood cells (WBC) between WB samples, PRP and platelet poor plasma (PPP) samples; and to analyze the concentrations of platelet-derived growth factor BB (PDGF-BB) and transforming growth factor ß1 (TGF-ß1) in the PRP and PPP of healthy adult cats using a standardized protocol with PRGF®-Endoret® characteristics. Material and Methods: WB was collected from 30 cats. PRP was obtained following three centrifugation protocols using PRGF®-Endoret® technology: 255, 260, and 265 g for 10 min each. The cellular components, RBC, WBC, PLT, and the concentrations of PDGF-BB and TGF-ß1 in the PRP and PPP fractions were determined for each protocol. Results: PLTs in the PRP fraction were statistically higher than WB, with no statistical differences between PPP and WB. In PRP fraction, PLT concentration was increased 1.4 times on average at 255 g; 1.3 times at 260 g and, 1.5 times at 265 g without statistical differences among them. The mean platelet volume (MPV) was significantly higher in WB compared to PRP and PPP fractions without significant differences between protocols. Compared to WB, the number of RBCs and WBCs was reduced by 99% and by more than 95% in PRP and PPP respectively, without significant differences between protocols. PDGF-BB concentrations were statistically higher in PRP than in PPP fractions, however, TGF-ß1 concentrations did not vary between fractions at 260 g. Comparing the three protocols within PRP and PPP fractions, no differences in PDGF-BB and TGF-ß1 concentrations were observed. Clinical Relevance: The study shows scientific evidence regarding the obtention of PRP in cats using the PRGF®-Endoret® technology for the quantification of PDGF-BB and TGF-ß1. At 265 g for 10 min, PLT concentration was increased 1.5 times with unnoticeable erythrocytes and leukocytes in the samples. These results clearly show that the PRGF®-Endoret® methodology is suitable to obtain PRP in cats. Further studies are needed to determine the clinical efficacy of the obtained PGRF in the treatment of different pathologies in cats.

Changes in Hematological and Biochemical Profiles in Ovariohysterectomized Bitches Using an Alfaxalone-Midazolam-Morphine-Sevoflurane Protocol.

The aim of this study was to monitor hematochemical changes during and after OHE in bitches. Twenty-four females were anesthetized with alfaxalone, midazolam, morphine and sevoflurane. Blood samples were taken before anesthesia (T0), at 30 (T1), and 60 min (T2), at 3 (T3), 6 (T4), 12 (T5), and 24 h (T6), and at 3 (T7) and 7 days (T8) from the start of surgery. Red blood cells (RBC) and packed cell volume (PCV) decreased significantly from T1 to T5 and hemoglobin (HB) concentration from T4 to T6. Both the white blood cell (WBC) and neutrophil (NFS) count increased significantly from T3 to T6, monocyte (MON) from T2 to T5, and eosinophil (EOS) at T5. Platelet (PLT) and plateletcrit (PCT) significantly decreased at T5 and increased from T6 to T8; platelet distribution width (PDW) increased significantly from T3 to T6. Creatine kinase (CK) activity increased significantly from T5 to T7. Glucose (GLU) concentrations increased significantly at T2 and P from T2 to T3. TG levels decreased from T2 to T4 and blood urea nitrogen (BUN) levels from T1 to T7, subsequently increasing until T8. Changes possibly resulting from stress and surgical trauma, as well as hemodilution and splenic storage, are due to anesthesia and surgery. In healthy bitches, these changes tend to gradually stabilize after the ending of OHE. A post-operative follow-up is essential to detect possible post-operative complications.

Treating Full Depth Cartilage Defects with Intraosseous Infiltration of Plasma Rich in Growth Factors: An Experimental Study in Rabbits.

OBJECTIVE: Intraarticular (IA) administration of platelet-rich plasma (PRP) has been proposed as a new strategy to halt osteoarthritis (OA) progression. In patients with severe OA, its potential is limited because it is unable to reach the subchondral bone, so a new strategy is needed, and intraosseous (IO) infiltration has been suggested. The purpose is to assess the impact of IA together with IO infiltration of plasma rich in growth factors (PRGF) in serum hyaluronic acid (HA) and type II collagen cleavage neoepitope (C2C) levels. DESIGN: A total of 32 rabbits were included in the study and randomly divided into 2 groups: control and treatment. A 4-mm chondral defect was created in the medial femoral condyle and IA followed by IO infiltration were performed. Serum C2C and HA levels were measured using enzyme-linked immunosorbent assay (ELISA) tests before infiltration and 28, 56, and 84 days post-infiltration. RESULTS: Significant lower C2C serum levels were obtained in treatment group (IA + IO infiltration of PRGF) at 84 days post-infiltration than in control group (IA infiltration of PRGF + IO infiltration of saline solution), while no significant differences between groups were reported at any other study times. Regarding HA, at 56 days post-infiltration, greater significant levels were seen in the treatment group. However, at 84 days post-infiltration, no significant differences were obtained, although lower levels were reported in the treatment group. CONCLUSIONS: Despite inconclusive, the results suggest that the combination of IA and IO infiltration with PRGF may enhance cartilage and subchondral bone regeneration, but further studies are needed.

Evaluation of Quadratus Lumborum Block as Part of an Opioid-Free Anaesthesia for Canine Ovariohysterectomy.

Quadratus lumborum block (QLB) is used to provide analgesia for abdominal surgery in humans. The aim of this study was to assess an anaesthetic protocol involving the QLB for canine ovariohysterectomy. Ten dogs were included. Anaesthetic protocol consisted of premedication with IM medetomidine (20 µg kg-1) and SC meloxicam (0.1 mg kg-1), induction with propofol to effect, and maintenance with sevoflurane in oxygen/medical air. QLB was performed injecting 0.4 mL kg-1 of 0.25% bupivacaine/iohexol per side. Computed Tomography (CT) was performed before and after surgery. Fentanyl was administered as rescue analgesia during surgery. The Short Form of The Glasgow Composite Pain Scale and thermal threshold (TT) at the level of the elbow, T10, T13 and L3 were assessed before premedication and every hour postoperatively. Methadone was given as rescue analgesia postoperatively when pain score was >3. A Yuen's test on trimmed means for dependent samples was used to analyse the data (p < 0.05). CT images showed spreading of the contrast/block for a median (range) of 3 (2-5) vertebrae, without differences between preoperative and postoperative images. One dog needed rescue analgesia during surgery. Pain score was less than 4/24 in all the animals during the first 4 h after surgery. TT showed a significant increased signal in all the areas tested, apart from the humerus, 30 min after surgery. The QLB may provide additional analgesia for canine ovariohysterectomy. Further studies are needed to assess the specific contribution of the QLB in abdominal analgesia.

Cell and Cell Free Therapies in Osteoarthritis.

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.

Changes in Acute Phase Proteins in Bitches after Laparoscopic, Midline, and Flank Ovariectomy Using the Same Method for Hemostasis.

Acute phase proteins (APP) are biomarkers of systemic inflammation, which allow monitoring the evolution of diseases, the response to treatments, and post-operative complications. Ovariectomy (OVE) is frequently performed in veterinary medicine and can be a useful model to evaluate surgical trauma and inflammation in the bitch. The objective was to investigate and compare the acute phase response (APR) after applying three different OVE techniques by measuring serum levels of C-reactive protein (CRP), haptoglobin (Hp), albumin (Alb), and paraoxonase-1 (PON-1). Forty-five intact bitches were included in the study, being randomly distributed into three groups: laparoscopic OVE (L), midline OVE (M), and flank OVE (F). Serum CRP, Hp, Alb, and PON-1 were measured before surgery, 1, 24, 72, and 168 h post-intervention. CRP levels increased significantly 24 h post-surgery in the M and F groups, but no significant variation was observed in the L group at any time of the study period. Hp was significantly higher in group L than in group F 72 h post-surgery. Alb and PON-1 showed no statistical difference among groups or among sampling periods. CRP response suggests that the use of laparoscopic procedures produce lower inflammation compared to open conventional approaches when performing OVE in the bitch.

Adipose-Derived Mesenchymal Stem Cells: A Promising Tool in the Treatment of Musculoskeletal Diseases.

Chronic musculoskeletal (MSK) pain is one of the most common medical complaints worldwide and musculoskeletal injuries have an enormous social and economical impact. Current pharmacological and surgical treatments aim to relief pain and restore function; however, unsatiscactory outcomes are commonly reported. In order to find an accurate treatment to such pathologies, over the last years, there has been a significantly increasing interest in cellular therapies, such as adipose-derived mesenchymal stem cells (AMSCs). These cells represent a relatively new strategy in regenerative medicine, with many potential applications, especially regarding MSK disorders, and preclinical and clinical studies have demonstrated their efficacy in muscle, tendon, bone and cartilage regeneration. Nevertheless, several worries about their safety and side effects at long-term remain unsolved. This article aims to review the current state of AMSCs therapy in the treatment of several MSK diseases and their clinical applications in veterinary and human medicine.