Feasibility and Safety of Endometrial Injection of Autologous Bone Marrow Mesenchymal Stem Cells in Mares

Abstract

Chronic degenerative endometritis (CDE) is an important cause of fertility problems in older mares. It is estimated that 30% of mares breeding are over 18 years old and the high value of their progeny encourages the use of these animals in assisted reproduction procedures. Currently, cell-based therapies are broadly used in human and veterinary regenerative medicine and have been showed a good effect on the treatment of liver fibrosis. Thus, the present study aimed to evaluate the feasibility and safety of endometrial injection of autologous bone marrow MSCs in mares. Mares were examined by transrectal ultrasound and the endometrial stem cells injections performed during diestrous, using injection needles coupled to a teflon catheter through the biopsy channel of a flexible endoscope. After treatment clinical evaluations (heart reat, respiratory rate, staining of the mucosa, capillary refill time, body temperature and lameness score) were performed daily during seven days. The intrauterine fluid and endometrial edema was evaluated before, 24 and 48 hours after the procedure by ultrasonographic exams and the inflammatory infiltrate (polymorphonuclear cells and mononuclear cells) and degree of fibrosis by histological evaluations before (D0) and 15 (D15), 30 (D30) and 60 (D60) days after endometrial injections. The results were evaluated by Kolmogorov-Smirnov and Kruskal-Wallis test followed by Dunn test and for fertility rates was used Chi-square, considering a 5% significance level. Neither clinical alteration was observed in mares after treatment, as well as, intrauterine fluid and endometrial edema were not detected in any mare before and after cell therapy. After cell therapy, significantly more PMNs were found in D15 biopsies, however, these cells were not observed in D30 and D60 biopsies. No worsening on the histological architecture after treatment was observed in any mare. In conclusion, the results of this study showed that endometrial hysteroscopic injections of stem cells in mares is a safe procedure.

Clinical safety of intratesticular transplantation of allogeneic bone marrow multipotent stromal cells in stallions

“…In both experiments, no clinical abnormalities were found in the application sites of allogeneic MSCs, which demonstrate the safety of this procedure, as reported by Alvarenga et al (), Maia et al (), Ferris et al (), Carradeet al() and Kol et al () using this therapy in other tissues.…”

“…In horses, MSCs therapy focused mainly on osteoarticular, tendinous lesions (Guest, Ousey, & Smith, ; Taylor, Smith, & Clegg, ) and intra‐articular injection (Ferris et al, ), with few reports of their use in other tissues. However, some studies demonstrated therapeutic benefits when MSCs were used in the uterus (Alvarenga et al, ). On the other hand, in equine testicles, there is a complete lack of information concerning MSCs administration.…”

Persistent Breeding-Induced Endometritis in Mares—A Multifaceted Challenge: From Clinical Aspects to Immunopathogenesis and Pathobiology

“…Injection [340] or infusion [341] of MSCs has been described as a possible alternative for the treatment of endometrial fibrosis. Therapy with MSCs can induce an early (7 days) and also a prolonged (60 days) remodeling of the endometrium of mares suffering from chronic-degenerative endometriosis by modulating the expression patterns (e.g., cytokeratin, vimentin, α-smooth muscle actin, and laminin) associated with the development of pathological fibrosis in the horse endometrium, as well as promoting glandular epithelial cells proliferation [341].…”

Methods of diagnosis of endometritis in mares

“…Apesar de a endometriose ser uma patologia degenerativa irreversível, existem estudos que avaliam a eficácia de alguns tratamentos para essa afecção uterina (Alvarenga et al, 2016, Mambelli et al, 2014. Um dos tratamentos para endometriose em éguas mais recentemente que tem sido estudado é com o uso de células tronco mesenquimais.…”