The Constantly Highly Expression of Limbal Stromal Cells Compared to the Bone Marrow Mesenchymal Stromal Cells, Adipose-Derived Mesenchymal Stromal Cells and Foreskin Fibroblasts

Human cornea on the front surface of eye is very critical for vision. The corneal transparency, continuous regeneration and functionality of corneal epithelium play an important role in refraction of light on to the retina. Corneal epithelium is regenerated by unique population of stem cells called limbal epithelial stem cells (LESC) that are located in the basal region of limbus. LESC differ from the corneal epithelium due to the lack of corneospecific differentiation keratins (K3/K12) expression [1-3], connexin 43mediated gap junction intercellular communication [4-6], p63 nuclear transcription factor [7,8], cell cycle duration [9], and label retaining property [10]. The limbalstroma provides a unique stem cell niche or microenvironment which is important for the modulation of stemness as it is heavily pigmented, highly innervated and vascularized. Clinically, destruction of LESC or the limbal stromal niche can lead to a pathological stage of LESC deficiency with severe loss of vision [11]. Chronic inflammation in the limbal deficient stroma is sufficient to cause detrimental damage to the conjunctivallimbalautograft transplanted to patients or experimental rabbits [12]. These findings suggest that the limbal stromal niche is critical in regulating the self-renewal and the fate of LESC. Although the mechanism remains elusive, modulation of epithelial proliferation, differentiation, proliferation and apoptosis by the limbalstroma has been reported to favor stemness [13]. Limbal stromal (LS) cells are very important component of limbal stromal niche that helps in self renewal of LESC. Recently, LS cells were shown to have multilineage differentiation potential [14-17]. In one of the studies, an ABCG2expressing FACS sorted side population cells from limbalstroma were able to differentiate into chondrocytes and neurons following differentiation induction [14]. In other studies, multipotent cells were also found in corneal stroma [15] and limbalstroma [16-17]. Earlier, we have reported that an ex vivo expanded LS cells possess multipotent differentiation potential towards adipocytes, osteocytes and chondrocytes [18]. Other stromal cells such as mesenchymal stem/stromal cells (MSC) can also be isolated and expanded in vitro for tissue regeneration applications [19-22]. MSC were first identified from bone marrow aspirates [23,24] and subsequently in Wharton's jelly of human umbilical cords [25], adipose tissue [26], dental tissues [27,28] and skin [29]. Most of the stromal cells derived from various sources expressed the markers of MSCs such as CD44, CD73, CD90, CD105, STRO1 and do not express markers of hematopoietic lineage such as CD14, CD34, CD45 and HLA-DR [30].