ABSTRACT
Ensuring the safety of mesenchymal stem cell (MSC) therapy is a fundamental requirement in clinical practice. This study aimed to assess the safety of using gonadal tissue-derived MSCs (n = 10) compared to the commonly utilized adipose tissue-derived MSCs (n = 9) in geriatric dogs with chronic diseases. All participants received allogeneic MSC therapy, and no allergic reactions due to allogeneic cell immunogenicity were noted. Both groups showed no adverse changes in physical exams or hematological parameters before and after therapy. Importantly, there were no instances of tumor formation or growth post-treatment in either group. The findings demonstrated that dogs treated with gonadal tissue-derived MSCs experienced no clinical adverse effects. However, clinical adverse effects were reported in one case of adipose tissue-derived MSC therapy. Despite limitations in monitoring beyond one year and constraints due to a small and diverse patient group, this pioneering study validates the safe use of gonadal tissue-derived MSCs in aged companion animals. It underscores the potential of utilizing tissues from neutering procedures to advance regenerative medicine and expand cell banks and therapy options for companion animals.
ABSTRACT
Mesenchymal stem cell (MSC) therapy has been actively applied in veterinary regenerative medicine to treat various canine and feline diseases. With increasing emphasis on safe cell-based therapies, evaluations of their tumorigenic potential are in great demand. However, a direct confirmation of whether tumors originate from stem cells or host cells is not easily achievable. Additionally, previous studies evaluating injections of high doses of MSCs into nude mice did not demonstrate tumor formation. Recent research focused on optimizing MSC-based therapies for veterinary patients, such as MSC-derived extracellular vesicles in treating different diseases. This progress also signifies a broader shift towards personalized veterinary medicine, where treatments can be tailored to individual pets based on their unique genetic profiles. These findings related to different treatments using MSCs emphasize their future potential for veterinary clinical applications. In summary, because of lower tumor-associated risk of MSCs as compared to embryonic and induced pluripotent stem cells, MSCs are considered a suitable source for treating various canine and feline diseases.
ABSTRACT
A 13-year-old neutered male Korean short-hair cat presented with anorexia, lethargy, and a severely distended abdomen, suggestive of ascites. Abdominocentesis yielded serosanguineous fluid. A subsequent diagnostic workup, including blood tests, ascitic fluid analysis, imaging studies [radiography, ultrasound, and computed tomography (CT)], and histopathological examination, was performed to identify the underlying cause. Imaging studies revealed characteristics of encapsulating peritoneal sclerosis (EPS) such as peritoneal thickening, fat stranding, and calcification. During laparotomy, fibrous membranes encapsulating the abdominal organs and ascites were observed, and multiple calcified regions were detected on the abdominal wall. Histopathological analysis confirmed the diagnosis of poorly differentiated invasive malignant neoplasms, which were further classified as carcinomatosis based on positive cytokeratin and negative vimentin immunohistochemistry results. To our knowledge, this is the first report of sclerosing peritoneal carcinomatosis with osseous metaplasia in a cat.
ABSTRACT
Canine mammary tumors (CMTs) are commonly observed in old and unspayed female dogs. Recently, dogs have been increasingly spaying at a young age to prevent mammary tumors. These CMTs require extensive local excision and exhibit a high probability of metastasis to the regional lymph nodes and lungs during malignancy. However, the molecular and biological mechanisms underlying CMT development have not been fully elucidated, and research in this area is limited. Therefore, in this study, we established new CMT cell lines by isolating cells from tumor tissues and investigated phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), a target for human breast cancer. PIK3CA mutations were observed at a similar loci as in the human PIK3CA gene in half of all canine samples. Furthermore, we investigated whether alpelisib, a PIK3CA inhibitor approved by the U.S. Food and Drug Administration for human breast cancer treatment, along with fulvestrant, is effective for CMT treatment. Alpelisib exerted stronger anticancer effects on cell lines with PIK3CA mutations than on the wild-type cell lines. In conclusion, we established new CMT cell lines with PIK3CA mutations and confirmed the efficacy of alpelisib for CMT treatment in vitro.
ABSTRACT
In this study, we document a case of phenobarbital-induced anticonvulsant hypersensitivity syndrome (AHS), which has been rarely reported in veterinary medicine. A 2-year-old, 5.4 kg, neutered male Russian Blue cat was diagnosed with idiopathic epilepsy and started on phenobarbital treatment. Eight days after initiation of phenobarbital treatment, the cat showed tachypnea and hyperthermia. CBC and serum biochemistry were unremarkable. However, the patient showed high serum amyloid A (SAA). On abdominal ultrasonography, generalized enlargement of abdominal lymph nodes and splenic multiple hypo-echoic nodules, which were consistent with reactive lymphadenopathy were found. The cat was diagnosed with AHS, and phenobarbital was discontinued. After 10 days of cessation, the patient had normal SAA, and clinical signs were resolved.