Abstract: Mesenchymal stem cells (MSCs) have emerged as a promising alternative for treating neurological disorders due to their neuroprotective, neuroregenerative, immunomodulatory, anti-inflammatory, and anti-apoptotic properties. The use of allogeneic MSCs offers advantages such as the selection of specific cells and their immediate availability. This study aimed to evaluate the safety and feasibility of intrathecal transplantation of allogeneic equine bone marrow-derived MSCs (EqBM-MSCs) in healthy horses. Ten healthy horses (five-12 years old) were randomly divided into two groups. In the control group (n = 5), phosphate-buffered saline was administered intrathecally, while the MSCs group (n = 5) received 3 × 10 allogeneic EqBM-MSCs. Safety and feasibility were assessed through physical examinations monthly for one year, cerebrospinal fluid (CSF) analysis before and six days after transplantation, and magnetic resonance imaging (MRI) one-year post-transplantation. No significant differences were found between the groups in physical examinations or CSF analysis before and six days after transplantation. Furthermore, MRI showed no changes after one year. Matrix Metalloproteinase-2 (MMP-2) expression was detected in the CSF before and after transplantation but showed no significant differences. These findings suggest that intrathecal transplantation of allogeneic EqBM-MSCs is safe and viable, offering a potential therapeutic approach for neurological disorders in horses.
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Overview
This study investigated the safety and feasibility of injecting allogeneic bone marrow-derived mesenchymal stem cells (MSCs) into the spinal fluid of healthy horses.
The findings indicate that this type of stem cell transplantation is safe, with no adverse effects observed over a year-long follow-up, suggesting potential for treating neurological diseases in horses.
Background
Mesenchymal Stem Cells (MSCs): Multipotent cells capable of differentiating into various cell types.
Therapeutic Properties:
Neuroprotective – helping to protect nerve cells from damage
Neuroregenerative – aiding in the repair and regeneration of nervous tissue
Immunomodulatory – modifying immune system responses
Anti-inflammatory – reducing inflammation
Anti-apoptotic – preventing programmed cell death
Allogeneic MSCs: Cells sourced from a donor rather than the recipient, allowing immediate use and selection of specific cell populations.
Study Design
Subjects: Ten healthy horses, aged 5 to 12 years.
Groups:
Control group (n=5): received intrathecal injection of phosphate-buffered saline (placebo).
MSC group (n=5): received intrathecal injection of 3 × 10^7 allogeneic equine bone marrow-derived MSCs (EqBM-MSCs).
Intrathecal Injection: Injection into the cerebrospinal fluid (CSF) space surrounding the spinal cord.
Duration: One-year follow-up period.
Assessment Methods
Physical Examinations: Conducted monthly to monitor general health and detect any adverse effects.
Cerebrospinal Fluid (CSF) Analysis:
Baseline samples collected before transplantation.
Follow-up samples collected six days post-transplantation to assess changes in CSF composition and inflammation markers.
Magnetic Resonance Imaging (MRI): Performed one year post-transplantation to detect any structural changes or damage in the central nervous system.
Matrix Metalloproteinase-2 (MMP-2) Monitoring: MMP-2, a protein involved in tissue remodeling and inflammation, was measured in CSF to evaluate biochemical responses to transplantation.
Key Findings
Physical Health: No significant differences or adverse effects were observed between treated and control horses over the one-year period.
CSF Analysis:
No significant differences before and six days after transplantation between groups.
MMP-2 levels were present in all horses but did not differ significantly after transplantation, suggesting no increased inflammatory response.
MRI Results: No observable structural changes or damage noted in any horses one year post-transplantation.
Conclusions and Implications
Intrathecal transplantation of allogeneic EqBM-MSCs in healthy horses is safe and feasible with no detectable adverse effects.
This method provides a potential new treatment avenue for equine neurological disorders, given the stem cells’ regenerative and protective properties.
The study supports the practicality of using donor-derived MSCs, which can be prepared and administered promptly without the delay of autologous cell harvesting.
Further studies may be warranted to evaluate efficacy in horses affected by neurological diseases and to optimize dosing and administration protocols.
Cite This Article
APA
de Oliveira Ferreira LV, Maia L, Barberini DJ, Takahira RK, de Vasconcelos Machado VM, Machado GF, de Melo GD, Amorim RM.
(2025).
Feasibility and safety of intrathecal transplantation of allogeneic bone marrow mesenchymal stem cells in horses.
Vet Res Commun, 49(6), 333.
https://doi.org/10.1007/s11259-025-10920-8
Department of Veterinary Clinic, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil.
Center for Translational Research in Regenerative Medicine - Institute of Biotechnology, São Paulo State University, Botucatu, São Paulo, Brazil.
Maia, Leandro
Department of Veterinary Clinic, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil.
Barberini, Danielle Jaqueta
Department of Veterinary Clinic, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil.
Takahira, Regina Kiomi
Department of Veterinary Clinic, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil.
de Vasconcelos Machado, Vânia Maria
Department of Veterinary Surgery and Animal Reproduction, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil.
Machado, Gisele Fabrino
Department of Clinic, Surgery and Animal Reproduction, São Paulo State University (UNESP), Araçatuba, São Paulo, Brazil.
de Melo, Guilherme Dias
Department of Clinic, Surgery and Animal Reproduction, São Paulo State University (UNESP), Araçatuba, São Paulo, Brazil.
Amorim, Rogério Martins
Department of Veterinary Clinic, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil. rogerio.amorim@unesp.br.
Center for Translational Research in Regenerative Medicine - Institute of Biotechnology, São Paulo State University, Botucatu, São Paulo, Brazil. rogerio.amorim@unesp.br.
Declarations. Consent for publication: Not applicable. Conflict of interest: The authors have no relevant financial or non-financial interests to disclose. Ethics approval: All phases of this study were approval from the Ethics Committee on Animal Use of UNESP – Botucatu. According to protocol number 76/2009-CEUA. All procedures were carried out in accordance with international guidelines for the care and use of experimental animals. Consent to participate: Not applicable. Clinical trial number: Not applicable.
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