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Stem cell research & therapy2018; 9(1); 96; doi: 10.1186/s13287-018-0849-6

Safety and tracking of intrathecal allogeneic mesenchymal stem cell transplantation in healthy and diseased horses.

Abstract: 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. Six healthy horses received 100 × 10 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 × 10 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. There 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. The 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.
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Publication Date: 2018-04-10 PubMed ID: 29631634PubMed Central: PMC5891950DOI: 10.1186/s13287-018-0849-6Google Scholar: Lookup
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  • Clinical Trial
  • Veterinary
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research paper assesses the safety and tracking of intrathecal administration of allogeneic mesenchymal stem cells in both healthy and diseased horses, their migration through the vertebral canal, and whether they can position themselves at the site of an injury.

Research Objectives

  • The research was conducted with three main objectives. Firstly, it aimed to determine the safety of injecting a high dose (100 million) of allogeneic adipose-derived mesenchymal stem cells (ASCs) intrathecally.
  • Secondly, the study aimed to observe how these ASCs are distributed after being injected in either the atlanto-occipital (AO) or the lumbosacral (LS) area in healthy horses.
  • Finally, the purpose of the study was to ascertain whether the ASCs hone towards the site of injury in horses suffering from neurological diseases.

Study Design and Methods

  • In the research, a total of six healthy horses were injected with the allogeneic ASCs. For two out of these six horses, the ASCs were labeled with technetium before being injected either at AO or LS.
  • Post this, daily neurological examinations were conducted and the blood and cerebrospinal fluid (CSF) were evaluated before and 30 days post-injection.
  • The distribution of these cells was then assessed through scintigraphic images obtained at different intervals after the injection.
  • Additionally, three diseased horses suffering from cervical vertebral compressive myelopathy (CVCM) were injected with green fluorescent protein (GFP) labeled ASCs and observed for one to two weeks before being euthanized for a complete nervous system examination.

Results and Findings

  • The study concluded that the injection of allogeneic ASCs was safe as there were no significant changes in blood, CSF, or neurological conditions in any of the horses.
  • Furthermore, the study found that the radioactive signal of ASCs could be traced to the lumbar area after an AO injection but only minimally after an LS injection.
  • However, the ASCs, labeled with GFP, could not be found at the site of disease in diseased horses even after a week or two weeks post-injection, indicating that the ASCs did not necessarily home to the site of injury.
  • The paper also noted that the intrathecal injection of ASCs was found to be easily performed in horses and that the AO administration of ASCs led to better distribution within the entire subarachnoid space in healthy horses.

Conclusions

  • The research concludes that the intrathecal injection of allogeneic ASCs seems to be safe and can be easily performed in horses.
  • However, although ASCs were well distributed within the subarachnoid space in healthy horses after AO administration, ASCs could not be found at the site of injury in horses with CVCM, suggesting that they may not home to the site of injury.

Cite This Article

APA
(2018). Safety and tracking of intrathecal allogeneic mesenchymal stem cell transplantation in healthy and diseased horses. Stem Cell Res Ther, 9(1), 96. https://doi.org/10.1186/s13287-018-0849-6

Publication

Stem cell research & therapy
ISSN: 1757-6512
NlmUniqueID: 101527581
Country: England
Language: English
Volume: 9
Issue: 1
Pages: 96
PII: 96

Researcher Affiliations

MeSH Terms

  • Adipose Tissue / cytology
  • Animals
  • Cell Movement
  • Cells, Cultured
  • Cerebrospinal Fluid / cytology
  • Female
  • Horse Diseases / therapy
  • Horses
  • Mesenchymal Stem Cell Transplantation / adverse effects
  • Mesenchymal Stem Cell Transplantation / methods
  • Mesenchymal Stem Cell Transplantation / veterinary
  • Mesenchymal Stem Cells / physiology
  • Random Allocation
  • Spinal Cord Compression / therapy
  • Spinal Cord Compression / veterinary
  • Transplantation, Homologous

Conflict of Interest Statement

ETHICS APPROVAL: The protocol (#18785, #18801) was reviewed and approved by the UC Davis IACUC on 2 June 2015. CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER’S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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