Abstract
BackgroundIt is currently unknown if the intrathecal administration of a high dose of allogeneic mesenchymal stem cells (MSCs) is safe, how MSCs migrate throughout the vertebral canal after intrathecal administration, and whether MSCs are able to home to a site of injury. The aims of the study were: 1) to evaluate the safety of intrathecal injection of 100 million allogeneic adipose-derived MSCs (ASCs); 2) to assess the distribution of ASCs after atlanto-occipital (AO) and lumbosacral (LS) injection in healthy horses; and 3) to determine if ASCs homed to the site of injury in neurologically diseased horses.MethodsSix healthy horses received 100 × 106 allogeneic ASCs via AO (n = 3) or LS injection (n = 3). For two of these horses, ASCs were radiolabeled with technetium and injected AO (n = 1) or LS (n = 1). Neurological examinations were performed daily, and blood and cerebrospinal fluid (CSF) were evaluated prior to and at 30 days after injection. Scintigraphic images were obtained immediately postinjection and at 30 mins, 1 h, 5 h, and 24 h after injection. Three horses with cervical vertebral compressive myelopathy (CVCM) received 100 × 106 allogeneic ASCs labeled with green fluorescent protein (GFP) via AO injection and were euthanized 1–2 weeks after injection for a full nervous system necropsy. CSF parameters were compared using a paired student’s t test.ResultsThere were no significant alterations in blood, CSF, or neurological examinations at any point after either AO or LS ASC injections into healthy horses. The radioactive signal could be identified all the way to the lumbar area after AO ASC injection. After LS injection, the signal extended caudally but only a minimal radioactive signal extended further cranially. GFP-labeled ASCs were not present at the site of disease at either 1 or 2 weeks following intrathecal administration.ConclusionsThe intrathecal injection of allogeneic ASCs was safe and easy to perform in horses. The AO administration of ASCs resulted in better distribution within the entire subarachnoid space in healthy horses. ASCs could not be found after 7 or 15 days of injection at the site of injury in horses with CVCM.
Highlights
It is currently unknown if the intrathecal administration of a high dose of allogeneic mesenchymal stem cells (MSCs) is safe, how Mesenchymal stem cell (MSC) migrate throughout the vertebral canal after intrathecal administration, and whether Mesenchymal stem cells (MSCs) are able to home to a site of injury
High-dose intrathecal administration of Adipose-derived mesenchymal stem cell (ASC) does not alter cerebrospinal fluid (CSF) parameters There were no statistical differences between AO and LS CSF parameters prior to or after ASC administration; as such, the groups were combined for further analysis
Data from this exploratory study suggest that the intrathecal administration of relatively high doses of allogeneic, culture-expanded ASCs is well tolerated in healthy horses regardless of whether the cells are administered at the AO or LS space
Summary
It is currently unknown if the intrathecal administration of a high dose of allogeneic mesenchymal stem cells (MSCs) is safe, how MSCs migrate throughout the vertebral canal after intrathecal administration, and whether MSCs are able to home to a site of injury. The aims of the study were: 1) to evaluate the safety of intrathecal injection of 100 million allogeneic adipose-derived MSCs (ASCs); 2) to assess the distribution of ASCs after atlanto-occipital (AO) and lumbosacral (LS) injection in healthy horses; and 3) to determine if ASCs homed to the site of injury in neurologically diseased horses. Site selection could depend on neuroanatomical localization of lesions (the administration site preferred closest to the lesion), the clinician’s expertise, patient cooperation, and pharmacological protocol (e.g., sedation versus general anesthesia) [31] It is currently unknown whether MSCs administered intrathecally would be able to migrate throughout the subarachnoid space and home to a diseased site. Developing protocols to administer allogeneic MSCs would permit immediate cell therapy in acute and subacute neurological diseases and would eliminate variation in ex vivo expansion that can hinder autologous cell use, especially in older animals and humans [32]
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