Safety and immunomodulatory effects of allogeneic canine adipose-derived mesenchymal stromal cells transplanted into the region of the lacrimal gland, the gland of the third eyelid and the knee joint

Shin Ae Park, Christopher M. Reilly, Joshua Wood, Dai Jung Chung, Danielle D. Carrade, Sarah L. Deremer, Rebecca L. Seraphin, Kaitlin C. Clark, Allison Zwingenberger, Dori L Borjesson, Kei Hayashi, Paul Russell, Christopher J Murphy

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Background aims: Mesenchymal stromal cells (MSCs) have been extensively studied as a cellular therapeutic for various pathologic conditions. However, there remains a paucity of data regarding regional and systemic safety of MSC transplantations, particularly with multiple deliveries of allogeneic cells. The purpose of this study was to investigate the safety and systemic immunomodulatory effects of repeated local delivery of allogeneic MSCs into the region of the lacrimal gland, the gland of the third eyelid and the knee joint in dogs. Methods: Allogeneic adipose tissue-derived canine MSCs were delivered to the regions of the lacrimal gland and the third eyelid gland as well as in the knee joints of six healthy laboratory beagles as follows: six times with 1-week intervals for delivery to the lacrimal gland and the third eyelid gland regions and three to four times with 1- to 2-week intervals for intra-articular transplantations. Dogs were sequentially evaluated by clinical examination. At the conclusion of the study, dogs were humanely euthanized, and a complete gross and histopathologic examination of all organ systems was performed. Mixed leukocyte reactions were also performed before the first transplantation and after the final transplantation. Results: Clinical and pathologic examinations found no severe consequences after repeated MSC transplantations. Results of mixed leukocyte reactions demonstrated suppression of T-cell proliferation after MSC transplantations. Conclusions: This is the first study to demonstrate regional and systemic safety and systemic immunomodulatory effects of repeated local delivery of allogeneic MSCs in vivo.

Original languageEnglish (US)
Pages (from-to)1498-1510
Number of pages13
JournalCytotherapy
Volume15
Issue number12
DOIs
StatePublished - Dec 2013

Keywords

  • Arthritis
  • Dry eye
  • Engraftment
  • Immunomodulation
  • Immunosuppression
  • KCS
  • Keratoconjunctivitis sicca
  • Osteoarthritis
  • Stifle joint
  • Toxicity

ASJC Scopus subject areas

  • Cell Biology
  • Cancer Research
  • Transplantation
  • Genetics(clinical)
  • Oncology
  • Immunology and Allergy
  • Immunology

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