TITLE:
Treatment of a mouse model of collagen antibody-induced arthritis with human adipose-derived secretions
AUTHORS:
Sinead P. Blaber, Rebecca A. Webster, Edmond J. Breen, Graham Vesey, Benjamin R. Herbert
KEYWORDS:
Collagen Antibody-Induced Arthritis (CAIA); Stromal Vascular Fraction (SVF); Adipocytes; Co-Culture; Secretions; Cytokines; Growth Factors; Bio-Plex; Rheumatoid Arthritis
JOURNAL NAME:
Open Journal of Regenerative Medicine,
Vol.2 No.3,
September
10,
2013
ABSTRACT: The use of
adipose-derived cells as a treatment for a variety of diseases is becoming
increasingly common. These therapies include the use of cultured mesenchymal stem
cells (MSCs) and freshly isolated stromal vascular fraction (SVF) alone, or in
conjunction with other cells such as adipocytes. There is a substantial amount
of literature published on the therapeutic properties of MSCs and their
secretions as the main driver of their therapeutic effect. However, there is
little data available on the therapeutic potential of secretions from SVF,
either with or without adipocytes. We investigated the ability of secretions
from human adipose SVF alone and the SVF co-cultured with adipocytes as a proxy
for cell therapy, to ameliorate an inflammatory disorder. This ethics approved
study involved the treatment of collagen antibody-induced arthritis (CAIA) in
mice with secretions from SVF, SVF co-cultured with adipocytes, or a vehicle
control via both intravenous (IV) and intramuscular (IM) routes. Treatment
outcome was assessed by paw volume, ankle size and clinical arthritis score
measurements. Serum samples were obtained following euthanasia and analysed for
a panel of 32 mouse cytokines and growth factors. The dose and timing regime
used for the IM administration of both human secretion mixtures did not
significantly ameliorate arthritis in this model. The IV administration of SVF
adipocyte co-culture secretions reduced the paw volume, and significantly
reduced the ankle size and clinical arthritis score when compared to the IV vehicle
control mice. This was a superior therapeutic effect than treatment with SVF
secretions. Furthermore, treatment with SVF adipocyte coculture secretions
resulted in a significant reduction in serum levels of key cytokines, IL-2 and
VEGF, involved in the pathogenesis of rheumatoid arthritis. Therefore, the SVF cocultured
with adipocytes is an attractive therapeutic for inflammatory conditions.