Stem Cell Therapy and Neurorehabilitation in Degenerative Myelopathy: A New Hope for Dogs

Degenerative myelopathy (DM) remains one of the most challenging neurodegenerative diseases affecting dogs, largely because no definitive cure currently exists. As the disease progresses, affected dogs gradually lose mobility due to spinal cord degeneration, often resulting in euthanasia within months of diagnosis^1,2. However, advances in regenerative medicine and neurorehabilitation are beginning to reshape the therapeutic landscape for canine DM. 

Regenerative medicine focuses on repairing damaged tissues and restoring function through cellular therapies, particularly stem cell-based approaches. Mesenchymal stem cells (MSCs), which are multipotent cells isolated from mature tissues, have attracted considerable attention because of their ability to modulate inflammation, promote tissue healing, and support neural regeneration^1,3,4. 

Why Stem Cells Matter in DM 

Recent studies have shown that MSC transplantation may provide neuroprotective benefits in neurodegenerative diseases such as ALS and DM^1,5,6. Rather than directly replacing damaged neurons, MSCs exert much of their therapeutic effect through paracrine signaling. These cells release bioactive molecules, including cytokines, growth factors, chemokines, glycoproteins, microvesicles, and exosomes, collectively known as the secretome⁷. 

These secreted factors support neural tissue repair by promoting neurogenesis, angiogenesis, remyelination, and axonal growth. Neurotrophic factors such as brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), nerve growth factor (NGF), fibroblast growth factor (FGF), neurotrophin-1 (NT-1), and neurotrophin-3 (NT-3) have all been associated with improved neuronal survival and reduced neurodegeneration¹. 

In veterinary medicine, MSC therapies have already been explored in spinal cord injuries, osteoarthritis, dermatitis, cartilage regeneration, chronic superficial keratitis, and other musculoskeletal disorders in dogs, showing promising regenerative effects¹. 

The Role of Intrathecal Stem Cell Administration¹ 

A recent prospective controlled blinded cohort clinical study conducted in Portugal between 2015 and 2023 evaluated dogs with DM undergoing intensive neurorehabilitation combined with intrathecal stem cell transplantation. The study included 13 dogs diagnosed through exclusion testing and confirmation of homozygous SOD1 gene mutation (DM/DM). 

The researchers specifically used synovial membrane-derived mesenchymal stem cells delivered intrathecally through the cerebrospinal fluid (CSF). This technique allows stem cells to bypass the blood-brain barrier and avoid pulmonary entrapment, enabling direct therapeutic action within the central nervous system. 

The results were encouraging. Dogs receiving intensive neurorehabilitation combined with stem cell transplantation demonstrated improved neurological function and significantly longer survival times compared to dogs undergoing rehabilitation alone. The mean survival time in the combined therapy group reached 438 days, compared to 274 days in the control rehabilitation group. One dog survived as long as 791 days. 

Improved Mobility and Quality of Life 

One of the most remarkable findings of the study was the improvement in ambulation. Most dogs in the intensive neurorehabilitation and stem cell protocol group achieved Open Field Scores (OFS) of 11 or higher, indicating functional walking ability^1,8. Significant improvements were observed between treatment phases, particularly after stem cell transplantation (p = 0.039). 

The benefits likely result from the combined effect of rehabilitation-induced neuroplasticity and the trophic support provided by MSCs. Researchers believe stem cells may help delay Wallerian degeneration, reduce inflammatory responses, recruit oligodendrocyte precursors, and stimulate surviving neural pathways to regain partial functionality¹. 

The study also highlighted the role of MSCs in potentiating aquaporin 1 and CXCR4 expression, two membrane proteins involved in cell migration and homing mechanisms that may improve therapeutic targeting within the nervous system¹. 

Conclusion 

Stem cell therapy is rapidly emerging as one of the most promising supportive approaches for degenerative myelopathy in dogs. Although further large-scale studies are still needed, the combination of MSC transplantation and intensive neurorehabilitation appears capable of improving neurological recovery, prolonging survival, and enhancing quality of life. Importantly, these findings may also contribute to broader advancements in regenerative medicine and neurodegenerative disease research relevant to both veterinary and human medicine. 

Reference 

1. Gouveia D, Correia J, Cardoso A, Carvalho C, Oliveira AC, Almeida A, Gamboa Ó, Ribeiro L, Branquinho M, Sousa A, Lopes B. Intensive neurorehabilitation and allogeneic stem cells transplantation in canine degenerative myelopathy. Frontiers in Veterinary Science. 2023 Jul 13;10:1192744. https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2023.1192744/pdf 

2. Kobatake Y, Nakata K, Sakai H, Sasaki J, Yamato O, Takashima S, Nishii N, Maeda S, Islam MS, Kamishina H. The long-term clinical course of canine degenerative myelopathy and therapeutic potential of curcumin. Veterinary sciences. 2021 Sep 12;8(9):192. https://www.mdpi.com/2306-7381/8/9/192 

3. Ratajczak MZ, Ratajczak J, Kucia M. Very small embryonic-like stem cells (VSELs) an update and future directions. Circulation Research. 2019 Jan 18;124(2):208-10. https://www.ahajournals.org/doi/pdf/10.1161/CIRCRESAHA.118.314287 

4. Mocchi M, Dotti S, Del Bue M, Villa R, Bari E, Perteghella S, Torre ML, Grolli S. Veterinary regenerative medicine for musculoskeletal disorders: can mesenchymal stem/stromal cells and their secretome be the new frontier?. Cells. 2020 Jun 11;9(6):1453. https://www.mdpi.com/2073-4409/9/6/1453 

5. Chudickova M, Vackova I, Machova Urdzikova L, Jancova P, Kekulova K, Rehorova M, Turnovcova K, Jendelova P, Kubinova S. The effect of Wharton jelly-derived mesenchymal stromal cells and their conditioned media in the treatment of a rat spinal cord injury. International journal of molecular sciences. 2019 Sep 12;20(18):4516. https://www.mdpi.com/1422-0067/20/18/4516 

6. Andrzejewska A, Lukomska B, Janowski M. Concise review: mesenchymal stem cells: from roots to boost. Stem cells. 2019 Jul 1;37(7):855-64. https://stemcellsjournals.onlinelibrary.wiley.com/doi/pdfdirect/10.1002/stem.3016 

7. Műzes G, Sipos F. Mesenchymal stem cell-derived secretome: a potential therapeutic option for autoimmune and immune-mediated inflammatory diseases. Cells. 2022 Jul 26;11(15):2300. https://www.mdpi.com/2073-4409/11/15/2300 

8. Lewis MJ, Jeffery ND, Olby NJ, Canine Spinal Cord Injury Consortium (CANSORT-SCI). Ambulation in dogs with absent pain perception after acute thoracolumbar spinal cord injury. Frontiers in veterinary science. 2020 Aug 26;7:560. https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2020.00560/pdf