Hindawi Publishing Corporation
Stem Cells International
Article ID 421253
Research Article
Alterations in the Secretome of Clinically Relevant
Preparations of Adipose-Derived Mesenchymal Stem Cells
Cocultured with Hyaluronan
Peter Succar,
1,2
Edmond J. Breen,
3
Donald Kuah,
4
and Benjamin R. Herbert
2,5
1
Department of Chemistry and Biomolecular Sciences, Macquarie University, Oice 256, Building E8C, Balaclava Road,
North Ryde, NSW 2109, Australia
2
Royal North Shore Hospital, University of Sydney, St Leonards, NSW 2065, Australia
3
Australian Proteome Analysis Facility, Macquarie University, North Ryde, NSW 2109, Australia
4
Sydney Sports Medicine Centre, 6 Figtree Drive, Sydney Olympic Park, NSW 2127, Australia
5
Regeneus Ltd., 25 Bridge Street, Pymble, NSW 2073, Australia
Correspondence should be addressed to Benjamin R. Herbert; benjamin.herbert@sydney.edu.au
Received 25 February 2015; Revised 10 June 2015; Accepted 11 June 2015
Academic Editor: Tong-Chuan He
Copyright © Peter Succar et al. his is an open access article distributed under the Creative Commons Attribution License, which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Osteoarthritis (OA) can be a debilitating degenerative disease and is the most common form of arthritic disease. here is a
general consensus that current nonsurgical therapies are insuicient for younger OA suferers who are not candidates for knee
arthroplasties. Adipose-derived mesenchymal stem cells (MSCs) therapy for the treatment of OA can slow disease progression
and lead to neocartilage formation. he mechanism of action is secretion driven. Current clinical preparations from adipose tissue
for the treatment of OA include autologous stromal vascular fraction (SVF), SVF plus mature adipocytes, and culture-puriied
MSCs. Herein we have combined these human adipose-derived preparations with Hyaluronan (Hylan G-F 20: Synvisc) in vitro
and measured alterations in cytokine proile. SVF plus mature adipocytes showed the greatest decreased in the proinlammatory
cytokines IL-1, IFN-, and VEGF. MCP-1 and MIP-1 decreased substantially in the SVF preparations but not the puriied MSCs.
he puriied MSC preparation was the only one to show increase in MIF. Overall the SVF plus mature adipocytes preparation
may be most suited of all the preparations for combination with HA for the treatment of OA, based on the alterations of heavily
implicated cytokines in OA disease progression. his will require further validation using in vivo models.
1. Introduction
Osteoarthritis (OA) can be a debilitating degenerative disease
and is the most common form of arthritic disease. Onset is
usually in the third and fourth decade of life and has a gradual
worsening prognosis over time.
OA is most prevalent in weight bearing joints; the highest
incidence of the disease occurs in the knee. It is classiied
as idiopathic and or secondary. Primary clinical interven-
tion currently involves limited systemic pharmacotherapy
such as analgesics and nonsteroidal anti-inlammatory drugs
(NSAIDs). Controlling mechanical overload through weight
loss and supporting braces can be used autonomously or
in combination with physical therapy. Viscosupplementation
can also be used to treat OA. his aims to replace lost
synovial luid in an OA knee with Hyaluronan (HA) to
reduce pain and increase mobility by lubricating the joint.
HA is an endogenous polysaccharide found in all tissues and
body luids of vertebrates. HA is especially abundant in loose
connective tissue and is a major component of cartilage [1]
and the synovium [2]. Aside from its rheological properties,
high molecular weight HA can decrease apoptosis, oxidative
stress, and necrosis [3].
Arthroscopic surgical interventions are used for the
debridement of mechanical cartilage tears, lesions, and
defects, as well as cartilage resurfacing or microfracture to