Dual-route administration of adipose tissue-derived mesenchymal stem cells (Ad-MSCs) for the treatment of spinal cord injury in a dog: a case report https://doi.org/10.12982/VIS.2026.086
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Abstract
Spinal cord injuries (SCIs) often lead to permanent neurological deficits and decreased quality of life for animals. While using traditional surgical and medical treatment is standard, using regenerative medicine, especially the use of mesenchymal stem cells (MSCs), is the therapeutic alternative. This case report illustrates a novel dual route of adipose derived-MSCs (Ad-MSCs) treatment approach to therapeutic outcome. A 5-year-old male French bulldog presented with sensory and motor incomplete signs, resulting in an inability to regulate both hindlimbs, urinary and defecation systems due to an injury to the thoracolumbar region of the spinal cord. Allogeneic Ad-MSCs, characterized according to established MSC criteria, were administered via a peripheral nerve route at a dose of 5x106 cells per each side for nerves and an intravenous route at a dose of 3x107 cells on day 133 after injury. An improvement in the paresis grade was observed after dual administration of Ad-MSCs. Within 4 weeks, the dog regained voluntary motor function, deep and superficial pain sensation, and the ability to stand up for defecation. No complications were observed during the follow-up period. This case suggests that the dual administration of Ad-MSCs is a safe and potentially effective treatment for spinal cord injuries in dogs.
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References
Al-Ameri, S., Zedan, Z., Al-Maliki, N., Hasan, A., 2026. Induced differentiation of adipose-derived stem cells into neuron-like cells to promote regeneration after sciatic nerve injury. J. Anim. Health Prod. 14(2), 428-434.
Bach, F.S., Rebelatto, C.L.K., Fracaro, L., Senegaglia, A.C., Fragoso, F.Y.I., Daga, D.R., Brofman, P.R.S., Pimpão, C.T., Engracia Filho, J.R., Montiani-Ferreira, F., 2019. Comparison of the efficacy of surgical decompression alone and combined with canine adipose tissue-derived stem cell transplantation in dogs with acute thoracolumbar disk disease and spinal cord injury. Front. Vet. Sci. 6, 450675.
Borodziuk, F., Borodziuk, B., Ciuba, K., Dąbrowska, P., Żuber, M., Bochyński, K., Molenda, K., Dacka, M., Giżewska, K., Białogłowski, K., 2024. Stem Cell Therapies for Spinal Cord Injury-A Review. Qual. Sport. 15, 52258-52258.
Chen, C.C., Yang, S.F., Wang, I.K., Hsieh, S.Y., Yu, J.X., Wu, T.L., Huang, W.J., Su, M.H., Yang, H.L., Chang, P.C., 2022. The long-term efficacy study of multiple allogeneic canine adipose tissue-derived mesenchymal stem cells transplantations combined with surgery in four dogs with lumbosacral spinal cord injury. Cell Transplant. 31.
Cheung, V., Hoshide, R., Bansal, V., Kasper, E., Chen, C.C., 2015. Methylprednisolone in the management of spinal cord injuries: Lessons from randomized, controlled trials. Surg Neurol Int. 6, 142.
Coates, J.R., Kube, S.A., Steinberg, H.S., 2026. Disorders of the canine spine and spinal cord. In: Chris, Z., Janet, B.V.D. (Eds.), Canine sports medicine and rehabilitation, 3rd edition. John Wiley & Sons, Hoboken, New Jersey, pp. 671-715.
Cooney, D.S., Wimmers, E.G., Ibrahim, Z., Grahammer, J., Christensen, J.M., Brat, G.A., Wu, L.W., Sarhane, K.A., Lopez, J., Wallner, C., Furtmüller, G.J., Yuan, N., Pang, J., Sarkar, K., Lee, W.P., Brandacher, G., 2016. Mesenchymal stem cells enhance nerve regeneration in a rat sciatic nerve repair and hindlimb transplant model. Sci. Rep. 6, 31306.
dos Santos Ramalho, B., de Almeida, F.M., Sales, C.M., De Lima, S., Martinez, A.M.B., 2018. Injection of bone marrow mesenchymal stem cells by intravenous or intraperitoneal routes is a viable alternative to spinal cord injury treatment in mice. Neural Regen. Res. 13(6), 1046-1053.
El Masri, J., Fadlallah, H., Al Sabsabi, R., Afyouni, A., Al-Sayegh, M., Abou-Kheir, W., 2024. Adipose-derived stem cell therapy in spinal cord injury. Cells. 13(17), 1505.
Fitch, M.T., Silver, J., 2008. CNS injury, glial scars, and inflammation: Inhibitory extracellular matrices and regeneration failure. Exp. Neurol. 209(2), 294-301.
Fu, X., Liu, G., Halim, A., Ju, Y., Luo, Q., Song, G., 2019. Mesenchymal stem cell migration and tissue repair. Cells. 8(8), 784.
Galea, M.P., Zyl, v.N., Messina, A., 2020. Peripheral nerve dysfunction after spinal cord injury. OBM Neurobiol. 4(4), 075.
Gao, J., Dennis, J.E., Muzic, R.F., Lundberg, M., Caplan, A.I., 2001. The dynamic in vivo distribution of bone marrow-derived mesenchymal stem cells after infusion. Cells Tissues Organs. 169(1), 12-20.
Gao, P., Zhou, Y., Xian, L., Li, C., Xu, T., Plunkett, B., Huang, S.-K., Wan, M., Cao, X., 2014. Functional effects of tgf-b1 on mesenchymal stem cell mobilization in cockroach allergen-induced asthma. J. Immunol. 192(10), 4560-4570.
Jamil, F., Ahmed, T., Iqbal, H., Vogt, A., Khan, W., 2025. Adipocyte-derived stem cells in the treatment of spinal cord injuries in animal models: a systematic review. Int. J. Mol. Sci. 26(19), 9330.
Kang, Y., Ding, H., Zhou, H., Wei, Z., Liu, L., Pan, D., Feng, S., 2017. Epidemiology of worldwide spinal cord injury: a literature review. J. Neurorestoratology. 6, 1-9.
Karakaş, N., Bay, S., Türkel, N., Öztunç, N., Öncül, M., Bilgen, H., Shah, K., Şahin, F., Öztürk, G., 2020. Neurons from human mesenchymal stem cells display both spontaneous and stimuli responsive activity. PLoS One. 15(5), e0228510.
Kengkla, P., Panyasing, Y., Thayananuphat, A., Tuntivanich, N., 2024. Effect of subconjunctival injection of canine adipose-derived mesenchymal stem cells on canine spontaneous corneal epithelial defects. Animals. 14(22), 3270.
Kim, Y., Jo, S.h., Kim, W.H., Kweon, O.K., 2015. Antioxidant and anti-inflammatory effects of intravenously injected adipose derived mesenchymal stem cells in dogs with acute spinal cord injury. Stem Cell Res. Ther. 6(1), 229.
Krueger, E., Magri, L.M., Botelho, A.S., Bach, F.S., Rebellato, C.L., Fracaro, L., Fragoso, F.Y., Villanova, J.A., Brofman, P.R., Popović-Maneski, L., 2017. Low-intensity electrical stimulation and stem cells in a dog with acute spinal cord injury. In 13th IASTED International Conference on Biomedical Engineering, Innsbruck, Austria, 20-21 February 2017.
Liau, L.L., Looi, Q.H., Chia, W.C., Subramaniam, T., Ng, M.H., Law, J.X., 2020. Treatment of spinal cord injury with mesenchymal stem cells. Cell Biosci. 10(1), 112.
Lima, R., Monteiro, A., Salgado, A.J., Monteiro, S., Silva, N.A., 2022. Pathophysiology and therapeutic approaches for spinal cord injury. Int. J. Mol. Sci. 23(22), 13833.
Liu, G., Zhao, Z., Wang, H., Hao, C., Wang, W., Zhang, C., Wang, T., Li, X., Xi, J., Li, S., 2022. Therapeutic efficacy of human mesenchymal stem cells with different delivery route and dosages in rat models of spinal cord injury. Cell Transplant. 31.
Mili, B., Buragohain, L., Ralte, L., Chutia, T., Gogoi, A., Barman, U., 2022. Application of mesenchymal stem cells for treating spinal cord injury in dogs: Mechanisms and their therapeutic efficacy. Indian J. Anim. Sci. 92(7), 806-813.
Mili, B., Choudhary, O.P., 2024. Advancements and mechanisms of stem cell-based therapies for spinal cord injury in animals. Int. J. Surg. 110(10), 6182-6197.
Morita, T., Sasaki, M., Kataoka-Sasaki, Y., Nakazaki, M., Nagahama, H., Oka, S., Oshigiri, T., Takebayashi, T., Yamashita, T., Kocsis, J.D., 2016. Intravenous infusion of mesenchymal stem cells promotes functional recovery in a model of chronic spinal cord injury. Neurosci. 335, 221-231.
Olby, N., 2010. The pathogenesis and treatment of acute spinal cord injuries in dogs. Vet. Clin. North Am. Small. Anim. Pract. 40(5), 791-807.
Olby, N., Levine, J., Harris, T., Muñana, K., Skeen, T., Sharp, N., 2003. Long-term functional outcome of dogs with severe injuries of the thoracolumbar spinal cord: 87 cases (1996-2001). J. Am. Vet. Med. Assoc. 222(6), 762-769.
Olsen, A., Johnson, V., Webb, T., Santangelo, K.S., Dow, S., Duerr, F.M., 2019. Evaluation of intravenously delivered allogeneic mesenchymal stem cells for treatment of elbow osteoarthritis in dogs: a pilot study. Vet. Comp. Orthop. Traumatol. 32(03), 173-181.
Osaka, M., Honmou, O., Murakami, T., Nonaka, T., Houkin, K., Hamada, H., Kocsis, J.D., 2010. Intravenous administration of mesenchymal stem cells derived from bone marrow after contusive spinal cord injury improves functional outcome. Brain Res. 1343, 226-235.
Oyinbo, C., 2011. Secondary injury mechanisms in traumatic spinal cord injury: a nugget of this multiply cascade. Acta Neurobiol. Exp. 71(2), 281-299.
Paśnicki, M., Król, A., Kosson, D., Kołacz, M., 2024. The safety of peripheral nerve blocks: the role of triple monitoring in regional anaesthesia, a comprehensive review. Healthcare. 12(7), 769.
Penha, E.M., Meira, C.S., Guimarães, E.T., Mendonça, M.V.P., Gravely, F.A., Pinheiro, C.M.B., Pinheiro, T.M.B., Barrouin-Melo, S.M., Ribeiro-dos-Santos, R., Soares, M.B.P., 2014. Use of autologous mesenchymal stem cells derived from bone marrow for the treatment of naturally injured spinal cord in dogs. Stem Cells Int. 2014, 437521.
Penn, M.S., 2010. SDF-1: CXCR4 axis is fundamental for tissue preservation and repair. Am. J. Pathol. 177(5), 2166-2168.
Pérez-Merino, E., Usón-Casaús, J., Zaragoza-Bayle, C., Duque-Carrasco, J., Mariñas-Pardo, L., Hermida-Prieto, M., Barrera-Chacón, R., Gualtieri, M., 2015. Safety and efficacy of allogeneic adipose tissue-derived mesenchymal stem cells for treatment of dogs with inflammatory bowel disease: Clinical and laboratory outcomes. Vet. J. 206(3), 385-390.
Rodríguez Sánchez, D.N., de Lima Resende, L.A., Boff Araujo Pinto, G., de Carvalho Bovolato, A.L., Possebon, F.S., Deffune, E., Amorim, R.M., 2019. Canine Adipose-Derived Mesenchymal Stromal Cells Enhance Neuroregeneration in a Rat Model of Sciatic Nerve Crush Injury. Cell Transplant. 28(1), 47-54.
Ryu, H.H., Kang, B.J., Park, S.S., Kim, Y., Sung, G.J., Woo, H.M., Kim, W.H., Kweon, O.K., 2012. Comparison of mesenchymal stem cells derived from fat, bone marrow, Wharton’s jelly, and umbilical cord blood for treating spinal cord injuries in dogs. J. Vet. Med. Sci. 74(12), 1617-1630.
Uccelli, A., Moretta, L., Pistoia, V., 2008. Mesenchymal stem cells in health and disease. Nat. Rev. Immunol. 8(9), 726-736.
van Middendorp, J.J., Hosman, A.J., Doi, S.A., 2013. The effects of the timing of spinal surgery after traumatic spinal cord injury: a systematic review and meta-analysis. J. Neurotrauma. 30(21), 1781-1794.
Vikartovska, Z., Kuricova, M., Farbakova, J., Liptak, T., Mudronova, D., Humenik, F., Madari, A., Maloveska, M., Sykova, E., Cizkova, D., 2020. Stem cell conditioned medium treatment for canine spinal cord injury: pilot feasibility study. Int. J. Mol. Sci. 21(14), 5129.
Vinícius de Oliveira Ferreira, L., Amorim, R.M., 2025. Mesenchymal stem cell-based therapeutic strategies for neurological disorders in dogs. In: Alvites, R.D., Maurício, A.C. (Eds.), Mesenchymal stem cells-biology, Therapeutics, and Beyond, IntechOpen, London.
Voga, M., Adamic, N., Vengust, M., Majdic, G., 2020. Stem cells in veterinary medicine-current state and treatment options. Front. Vet. Sci. 7, 278.
Wang, S., Guo, L., Ge, J., Yu, L., Cai, T., Tian, R., Jiang, Y., Zhao, R.C., Wu, Y., 2015. Excess integrins cause lung entrapment of mesenchymal stem cells. Stem Cells. 33(11), 3315-3326.
Yang, Z., Zheng, C., Zhang, F., Lin, B., Cao, M., Tian, X., Zhang, J., Zhang, X., Shen, J., 2020. Magnetic resonance imaging of enhanced nerve repair with mesenchymal stem cells combined with microenvironment immunomodulation in neurotmesis. Muscle Nerve. 61(6), 815-825.
Yeh, D.C., Chan, T.M., Harn, H.J., Chiou, T.W., Chen, H.S., Lin, Z.S., Lin, S.Z., 2015. Adipose tissue-derived stem cells in neural regenerative medicine. Cell Transplant. 24(3), 487-492.
Zhang, Q., Nguyen, P., Xu, Q., Park, W., Lee, S., Furuhashi, A., Le, A.D., 2017. Neural progenitor-like cells induced from human gingiva-derived mesenchymal stem cells regulate myelination of Schwann cells in rat sciatic nerve regeneration. Stem Cells Transl. Med. 6(2), 458-470.
Zhang, X., Kuang, Q., Xu, J., Lin, Q., Chi, H., Yu, D., 2024. MSC-based cell therapy in neurological diseases: a concise review of the literature in pre-clinical and clinical research. Biomolecules. 14(5), 538.
Zou, C., Song, G., Luo, Q., Yuan, L., Yang, L., 2011. Mesenchymal stem cells require integrin β1 for directed migration induced by osteopontin in vitro. In Vitro Cell Dev. Biol. Animal. 47(3), 241-250.
