vIL-10-overexpressing human MSCs modulate naïve and activated T lymphocytes following induction of collagenase-induced osteoarthritis

Stem Cell Res Ther. 2016 May 18;7(1):74. doi: 10.1186/s13287-016-0331-2.

Abstract

Background: Recent efforts in osteoarthritis (OA) research have highlighted synovial inflammation and involvement of immune cells in disease onset and progression. We sought to establish the in-vivo immune response in collagenase-induced OA and investigate the ability of human mesenchymal stem cells (hMSCs) overexpressing viral interleukin 10 (vIL-10) to modulate immune populations and delay/prevent disease progression.

Methods: Eight-week-old male C57BL/6 mice were injected with 1 U type VII collagenase over two consecutive days. At day 7, 20,000 hMSCs overexpressing vIL-10 were injected into the affected knee. Control groups comprised of vehicle, 20,000 untransduced or adNull-transduced MSCs or virus alone. Six weeks later knees were harvested for histological analysis and popliteal and inguinal lymph nodes for flow cytometric analysis.

Results: At this time there was no significant difference in knee OA scores between any of the groups. A trend toward more damage in animals treated with hMSCs was observed. Interestingly there was a significant reduction in the amount of activated CD4 and CD8 T cells in the vIL-10-expressing hMSC group.

Conclusions: vIL-10-overexpressing hMSCs can induce long-term reduction in activated T cells in draining lymph nodes of mice with collagenase-induced OA. This could lead to reduced OA severity or disease progression over the long term.

Keywords: Cell therapy; Collagenase-induced osteoarthritis; Gene therapy; Mesenchymal stem cell; Xenogeneic; vIL-10.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviruses, Human / genetics
  • Adenoviruses, Human / metabolism
  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / pathology
  • Cell- and Tissue-Based Therapy / methods
  • Collagenases
  • Gene Expression
  • Genetic Vectors / genetics
  • Genetic Vectors / metabolism
  • Humans
  • Immunomodulation
  • Interleukin-10 / genetics*
  • Interleukin-10 / immunology
  • Knee Joint / immunology
  • Knee Joint / pathology
  • Lymphocyte Activation
  • Male
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Osteoarthritis / chemically induced
  • Osteoarthritis / immunology
  • Osteoarthritis / pathology
  • Osteoarthritis / therapy*
  • Transgenes*

Substances

  • IL10 protein, human
  • Interleukin-10
  • Collagenases