Immunosuppressive properties of mesenchymal stromal cell cultures derived from the limbus of human and rabbit corneas

Bray, Laura J., Heazlewood, Celena F., Munster, David J., Hutmacher, Dietmar W., Atkinson, Kerry and Harkin, Damien G. (2014) Immunosuppressive properties of mesenchymal stromal cell cultures derived from the limbus of human and rabbit corneas. Cytotherapy, 16 1: 64-73. doi:10.1016/j.jcyt.2013.07.006


Author Bray, Laura J.
Heazlewood, Celena F.
Munster, David J.
Hutmacher, Dietmar W.
Atkinson, Kerry
Harkin, Damien G.
Title Immunosuppressive properties of mesenchymal stromal cell cultures derived from the limbus of human and rabbit corneas
Journal name Cytotherapy   Check publisher's open access policy
ISSN 1465-3249
1477-2566
Publication date 2014-01-01
Year available 2013
Sub-type Article (original research)
DOI 10.1016/j.jcyt.2013.07.006
Volume 16
Issue 1
Start page 64
End page 73
Total pages 10
Place of publication Oxford, United Kingdom
Publisher Elsevier
Language eng
Formatted abstract
Background aims
Mesenchymal stromal cells (MSCs) cultivated from the corneal limbus (L-MSCs) provide a potential source of cells for corneal repair. In the present study, we investigated the immunosuppressive properties of human L-MSCs and putative rabbit L-MSCs to develop an allogeneic therapy and animal model of L-MSC transplantation.

Methods
MSC-like cultures were established from the limbal stroma of human and rabbit (New Zealand white) corneas using either serum-supplemented medium or a commercial serum-free MSC medium (MesenCult-XF Culture Kit; Stem Cell Technologies, Melbourne, Australia). L-MSC phenotype was examined by flow cytometry. The immunosuppressive properties of L-MSC cultures were assessed using mixed leukocyte reactions. L-MSC cultures were also tested for their ability to support colony formation by primary limbal epithelial (LE) cells.

Results
Human L-MSC cultures were typically CD34, CD45 and HLA-DRand CD73+, CD90+, CD105+ and HLA-ABC+. High levels (>80%) of CD146 expression were observed for L-MSC cultures grown in serum-supplemented medium but not cultures grown in MesenCult-XF (approximately 1%). Rabbit L-MSCs were approximately 95% positive for major histocompatibility complex class I and expressed lower levels of major histocompatibility complex class II (approximately 10%), CD45 (approximately 20%), CD105 (approximately 60%) and CD90 (<10%). Human L-MSCs and rabbit L-MSCs suppressed human T-cell proliferation by up to 75%. Conversely, L-MSCs from either species stimulated a 2-fold to 3-fold increase in LE cell colony formation.

Conclusions
L-MSCs display immunosuppressive qualities in addition to their established non-immunogenic profile and stimulate LE cell growth in vitro across species boundaries. These results support the potential use of allogeneic L-MSCs in the treatment of corneal disorders and suggest that the rabbit would provide a useful pre-clinical model.
Keyword Cell therapy
Corneal limbus
Immunosuppression
Mesenchymal stromal cells
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
 
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