Abstract
In the mid-1980s we produced and characterised several monoclonal antibodies ‘mAbs 3-B-3(−); 4-C-3, 6-C-3 & 7-D-4) that recognised unique native sulphation motifs in chondroitin sulphate (CS) glycosaminoglycan (GAG) chains on connective tissue proteoglycans (PGs).
These antibodies were shown to specifically locate CS-PGs in the pericellular regions surrounding putative sites where haemopoietic stem cells were undergoing lymphopoiesis in the Bursa of Fabricius of embryonic chicks. In later studies, we also observed immunostaining for some of these mAbs ‘3-B-3(-) & 7-D-4’ in chondrocyte clusters present in tissue sections from late-stage osteoarthritic cartilage from canine and human patients. In a recent study ‘Hayes et al (2008), J. Histochem Cytochem. 56: 125–128’ we have used these anti-CS sulphation motif mAbs to specifically identify stem/chondroprogenitor cells in the surface/superficial zone of hyaline articular cartilage. Furthermore, we used these mAbs in FACS analyses to sort and isolate chondroprogenitor cells for potential pluripotent cell enrichment in tissue engineering/tissue regeneration technologies. We have also used several of these mAbs to identify stem/progenitor cells in different anatomical and functional regions of the tendon; i.e. where the tendon wraps around bone in compressed regions where the cells exhibit a more chondrogenic phenotype and also in the outer zones of the tendon surrounding pericytes where vascularisation occurs. In the developing intervertebral some of these mAbs specifically recognise stem/progenitor cells at the interzone between the outer and inner anulus an also the boundary of the nucleus with the inner annulus, these results indicating their use for stem/progenitor cell identification and isolation in other musculoskeletal tissues. Interestingly, these mAbs also immunostained the pericellular environment (stem cell niche) in the crypts of the gut and the limbus of the eye where stem cells reside. Collectively, this data strongly suggests that these mAbs recognising CS sulphation motifs can be used as biomarkers to identify stem cell niches in numerous tissues of the body and that they can be used for stem/progenitor cell isolation for use in tissue engineering/regeneration procedures.
This work was supported by BBSRC and ARC funding.
Correspondence should be addressed to Dr Roger Bayston, Division of Orthopaedic and Accident Surgery, Queen’s Medical Centre, Nottingham, NG7 2UH, England.
