Musculoskeletal injuries such as equine osteoarthritis, osteoarticular defects, tendonitis/desmitis, and muscular disorders are prevalent among sport horses, with a fair prognosis for returning to exercise or previous performance levels. The field of equine medicine has witnessed rapid and fruitful development, resulting in a diverse range of therapeutic options for musculoskeletal problems. Staying abreast of these advancements can be challenging, prompting the need for a comprehensive review of commonly used and recent treatments. The aim is to compile current therapeutic options for managing these injuries, spanning from simple to complex physiotherapy techniques, conservative treatments including steroidal and non-steroidal anti-inflammatory drugs, hyaluronic acid, polysulfated glycosaminoglycans, pentosan polysulfate, and polyacrylamides, to promising regenerative therapies such as hemoderivatives and stem cell-based therapies. Each therapeutic modality is scrutinized for its benefits, limitations, and potential synergistic actions to facilitate their most effective application for the intended healing/regeneration of the injured tissue/organ and subsequent patient recovery. While stem cell-based therapies have emerged as particularly promising for equine musculoskeletal injuries, a multidisciplinary approach is underscored throughout the discussion, emphasizing the importance of considering various therapeutic modalities in tandem.

Advances in hiPSC isolation and reprogramming and hPSC-CM differentiation have prompted their therapeutic application and utilization for evaluating potential cardiovascular safety liabilities. In this perspective, we showcase key efforts toward the large-scale production of hiPSC-CMs, implementation of hiPSC-CMs in industry settings, and recent clinical applications of this technology. The key observations are a need for traceable gender and ethnically diverse hiPSC lines, approaches to reduce cost of scale-up, accessible clinical trial datasets, and transparent guidelines surrounding the safety and efficacy of hiPSC-based therapies.

BACKGROUND: Regenerative techniques combined with core decompression (CD) are commonly used to treat osteonecrosis of the femoral head (ONFH). However, no consensus exists on regeneration therapy combined with CD that performs optimally. Therefore, we evaluated six regenerative therapies combined with CD treatment using a Bayesian network meta-analysis (NMA).
METHODS: We searched PubMed, Embase, Cochrane Library, and Web of Science databases. Six common regeneration techniques were categorized into the following groups with CD as the control group: (1) autologous bone graft (ABG), (2) autologous bone graft combined with bone marrow aspirate concentrate (ABG + BMAC), (3) bone marrow aspirate concentrate (BMAC), (4) free vascular autologous bone graft (FVBG), (5) expanded mesenchymal stem cells (MSCs), and (6) platelet-rich plasma (PRP). The conversion rate to total hip arthroplasty (THA) and progression rate to femoral head necrosis were compared among the six treatments.
RESULTS: A total of 17 literature were included in this study. In the NMA, two of the six treatment strategies demonstrated higher response in preventing the progression of ONFH than CD: MSCs (odds ratio [OR]: 0.098, 95% confidence interval [CI]: 0.0087-0.87) and BMAC (OR: 0.27, 95% CI: 0.073-0.73). Additionally, two of the six treatment strategies were effective techniques in preventing the conversion of ONFH to THA: MSCs (OR: 0.062, 95% CI: 0.0038-0.40) and BMAC (OR: 0.32, 95% CI: 0.1-0.074). No significant difference was found among FVBG, PRP, ABG + BMAC, ABG, and CD in preventing ONFH progression and conversion to THA (P > 0.05).
CONCLUSIONS: Our NMA found that MSCs and BMAC were effective in preventing ONFH progression and conversion to THA among the six regenerative therapies. According to the surface under the cumulative ranking value, MSCs ranked first, followed by BMAC. Additionally, based on our NMA results, MSCs and BMAC following CD may be necessary to prevent ONFH progression and conversion to THA. Therefore, these findings provide evidence for the use of regenerative therapy for ONFH.

BACKGROUND: After Alzheimer\'s disease, the second slot for the most common neurodegenerative disease, is occupied by Parkinson\'s disease. The symptoms of Parkinson\'s are classified as motor symptoms and non-motor symptoms. Motor symptoms involve rigidity, tremors, bradykinesia, and postural instability. Non-motor symptoms consist of cognitive dysfunction, salivation, lacrimation, etc. Objectives: The objectives of this study are to find out the most recent treatment options for Parkinson\'s disease.
METHODS: Research and review papers are collected from different databases like Google Scholar, PubMed, Mendeley, Scopus, Science Open, and the Directory of Open Access Journals using different keywords such as \"Parkinson\'s disease, biomarkers, animal models\".
RESULTS: Currently, various novel therapeutics have been emerging for PD. These may include treatments that may control the symptoms without causing any other severe side effects with already available treatments. Better therapies such as gene therapies, cell-based treatments, and regenerative therapies, which may evolve over time, can be a better therapeutic option.
CONCLUSIONS: There is a need for the development of novel and potential therapeutic strategies that offer fewer side effects to patients. Several clinical, biochemical, and imaging markers that are noteworthy in Parkinson\'s disease examination have been discussed here. Current work in the field of Parkinson\'s disease has developed a variety of significant small animal models, such as viral vector models and seeding models, including the insertion of preformed fibrils of alpha-synuclein. The brief concepts regarding risk factors, pathogenesis, clinical diagnosis, and emerging treatments of PD are discussed in this review article.

Aural hematoma is a common pathological condition in veterinary practice with a high incidence rate in dogs. Drainage, corticosteroid injections, and surgical approaches represent the common treatments in these clinical cases. However, surgery leaves visible signs and is usually correlated with recurrence, scars, and deformation of the treated pinna. For this reason, more effective and less invasive methods have been proposed over the years. Platelet-Rich Plasma (PRP) is one of the most promising options due to its pro-regenerative properties and capability to modulate the inflammatory state. The present work reports 12 cases of canine aural hematoma treated with PRP. The PRP treatment was combined with an ultrasound evaluation of the pinna to detect and treat all involved septa. The results show that relatively large volumes (2 mL) of PRP associated with an ultrasound guide are safe and efficacious in the treatment of canine aural hematoma requiring a maximum of two infiltrations, both in acute and chronic conditions. All the patients recovered their normal ear thickness (compared with the controlateral one) without relapses, averaging 38.5 days from their first treatment (10-90 days; SD: 24.7). The key role of PRP combined with a tailored diagnosis process carried out by the veterinarian, which included using an ultrasound system and the proper bandage, suggests that this approach may represent a valid alternative to surgery and corticosteroids.

Spinal cord injury (SCI) can lead to severe neurological dysfunction. Despite scientific and medical advances, clinically effective regenerative therapies including stem cells are lacking for SCI.
This paper discusses translational challenges related to the safe, effective use of stem cells for SCI, with a focus on mesenchymal stem cells (MSCs), neural stem cells (NSCs), Schwann cells (SCs), olfactory ensheathing cells (OECs), oligodendrocyte precursor cells (OPCs), embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs). We discuss approaches to enhance the efficacy of cell-based strategies by i) addressing patient heterogeneity and enhancing patient selection; ii) selecting cell type, cell source, cell developmental stage, and delivery technique; iii) enhancing graft integration and mitigating immune-mediated graft rejection; and iv) ensuring availability of cells. Additionally, we review strategies to optimize outcomes including combinatorial use of rehabilitation and discuss ways to mitigate potential risks of tumor formation associated with stem cell-based strategies.
Basic science research will drive translational advances to develop stem cell-based therapies for SCI. Genetic, serological, and imaging biomarkers may enable individualization of cell-based treatments. Moreover, combinatorial strategies will be required to enhance graft survival, migration and functional integration, to enable precision-based intervention.

Background and objectives: Cartilage surgery constitutes a standard intervention in foot and ankle procedures. Currently, there is a lack of epidemiological data on its frequency, age distribution, and surgical options for cartilage surgery. This study aimed to investigate the current landscape of cartilage surgery in Germany and identify the most common procedures from an epidemiological standpoint. Materials and methods: Medical billing and reporting data from the Federal Statistical Office of Germany, encompassing the period 2006-2020, was examined, including all foot and ankle cartilage surgical procedures (summarized under OPS codes 5-812 and 5-801). The dataset incorporated information on the affected joint, patient age and sex, and surgery type. Each surgical procedure was categorized as \"debridement\", \"regeneration\" or \"refixation\". Linear and nonlinear regression analyses were employed, with a statistical significance threshold of 0.05. Results: From the total of 136,501 procedures conducted during the study period, the most frequently performed interventions were microfracture (58,252) and chondroplasty (56,135), and thus, debridement procedures were in the leading position. The use of acellular membranes was the most used regenerative technique (n = 11,414). At the ankle joint, interventions were mostly arthroscopic and in men, while foot cartilage surgeries were preferably performed via open surgery and mostly in women. Age distribution analysis revealed two primary peaks: the first in the 20-25-year-old group (ankle and foot) and the second in the 45-50-year-old group (ankle) and 55-60-year-old group (foot). Refixation and regenerative procedures were more frequent among younger individuals, while debriding procedures were more frequent among older individuals. Regenerative procedures, particularly in the ankle, significantly increased over time. Conclusions: Cartilage surgery of the foot and ankle was common, with two primary age groups predominantly affected. Notably, recent years have witnessed a considerable rise in cartilage regenerative procedures.

It is assumed that all species, including sheep, demonstrate significant variation between individuals including the characteristics of their bone marrow-derived mesenchymal stem cells (BM-MSCs). These differences may account for limited success in pre-clinical animal studies and may also impact on treatment strategies that are used within regenerative medicine. This study investigates variations between ovine MSCs (oMSCs) isolated from 13 English Mule sheep donors by studying cell viability, expansion, the cells\' trilineage differentiation potential and the expression of cell surface markers. In addition to the primary objective, this article also compares various differentiation media used for the trilineage differentiation of oMSCs. In this study, a clear individual variation between the sheep donors regarding oMSCs characterization, tri-lineage differentiation potential and marker expression was effectively demonstrated. The results set out to systematically explore the ovine mesenchymal stem cell population derived from multiple donors. With this information, it is possible to start addressing the issues of personalized approaches to regenerative therapies.

Platelet-rich plasma (PRP) therapy is increasingly popular to treat musculoskeletal diseases, including tendinopathies and osteoarthritis (OA). To date, it remains unclear to which extent PRP compositions are determined by the immune cell and cytokine profile of individuals or by the preparation method. To investigate this, we compared leukocyte and cytokine distributions of different PRP products to donor blood samples and assessed the effect of pro-inflammatory cytokines on chondrocytes.
For each of three PRP preparations (ACP®, Angel™, and nSTRIDE® APS), products were derived using whole blood samples from twelve healthy donors. The cellular composition of PRP products was analyzed by flow cytometry using DURAClone antibody panels (DURAClone IM Phenotyping Basic and DURAClone IM T Cell Subsets). The MESO QuickPlex SQ 120 system was used to assess cytokine profiles (V-PLEX Proinflammatory Panel 1 Human Kit, Meso Scale Discovery). Primary human chondrocyte 2D and 3D in vitro cultures were exposed to recombinant IFN-γ and TNF-α. Proliferation and chondrogenic differentiation were quantitatively assessed.
All three PRP products showed elevated portions of leukocytes compared to baseline levels in donor blood. Furthermore, the pro-inflammatory cytokines IFN-γ and TNF-α were significantly increased in nSTRIDE® APS samples compared to donor blood and other PRP products. The characteristics of all other cytokines and immune cells from the donor blood, including pro-inflammatory T cell subsets, were maintained in all PRP products. Chondrocyte proliferation was impaired by IFN-γ and enhanced by TNF-α treatment. Differentiation and cartilage formation were compromised upon treatment with both cytokines, resulting in altered messenger ribonucleic acid (mRNA) expression of collagen type 1A1 (COL1A1), COL2A1, and aggrecan (ACAN) as well as reduced proteoglycan content.
Individuals with elevated levels of cells with pro-inflammatory properties maintain these in the final PRP products. The concentration of pro-inflammatory cytokines strongly varies between PRP products. These observations may help to unravel the previously described heterogeneous response to PRP in OA therapy, especially as IFN-γ and TNF-α impacted primary chondrocyte proliferation and their characteristic gene expression profile. Both the individual\'s immune profile and the concentration method appear to impact the final PRP product.
This study was prospectively registered in the Deutsches Register Klinischer Studien (DRKS) on 4 November 2021 (registration number DRKS00026175).

Cite this article: Bone Joint Res 2023;12(1):5-8.