In this study, we identified a unique MSC population residing in the mouse sclera, which we have termed SSPCs. SSPCs posses the capacity for self-renewal and multipotent differentiation. The isolation and characterization of SSPCs may provide a new tool for the study of basic biology of the sclera.
The sclera exhibits low cellularity compared with most vascularized tissues. It was considered that sclera cells are quiescence residents between fibrous layers.23
Cell-based studies of the sclera often use explants to obtain cell cultures.24–26
Approximately 10 to 14 days after explantation, the cells, termed sclerocytes, rapidly transform into active “scleral fibroblasts.” These characteristics of cell proliferation and transformation hint at the possibility that stem/progenitor cells reside in the sclera. These scleral fibroblasts or part of them may be stem/progenitor cells that have not been identified.
SSPCs failed to undergo osteogenic differentiation when cultured in osteoinductive medium or after in vivo transplantation. It has been reported that gingival stem/progenitor cells also cannot form mineralized tissue in vivo.27
SSPCs may need additional supplemental growth factors, such as BMPs, for further induction of osteocytes rather than only osteoinductive medium. The fate of in vivo lineage commitment by MSCs depends on multiple factors such as different tissue origins, the hierarchy of lineage commitment, cell culture conditions, local growth factors, and transplantation conditions (carriers and recipients).28,29
Seko et al.13
showed that explants from human scleral tissue possessed a chondrogenic lineage potential. They described how the sclera of certain vertebrates, such as birds and fish, is composed of hyaline cartilage. Although the human sclera is not a cartilaginous tissue, the human sclera has maintained chondrogenic potential throughout evolution. In addition, they directly explain the enigma of why the sclera and the joint cartilage are common targets of inflammatory cells in rheumatic arthritis. These cells may play a role in inflammatory and immune response of scleritis. Further study for the relationship between SSPCs and immune response is worth performing.
SSPCs may be a resource for the bioengineering of artificial scleras and for cell-based therapy. Myopia has become a public health issue worldwide.30–34
High myopia is associated with an increased risk for several ocular diseases such as cataract, glaucoma, retinal detachment, myopic retinal degeneration, visual impairment, and blindness.35–38
The detailed mechanism of myopia development is unknown. Scleral tissue may be responsible for myopia development due to its significant structure alteration in myopia.39
SSPCs may help to clarify the pathogenesis of developmental diseases such as childhood myopia and remain a source for further studies.
A mouse model of myopia was established in 2008,40
and as a result of the recent complete genomic sequence disclosure, the mouse eye has become a very important model for research on eye growth and myopia. In addition, sclera diseases such as refractory scleritis and scleromalacia are also difficult to cure and lead to blindness. Scleritis is often the initial or only indication of severe and life-threatening systemic autoimmune diseases such as rheumatoid arthritis, Wegener's granulomatosis, systemic lupus erythematosus, and relapsing polychondritis.41,42
An autoimmune dysregulation in a genetically predisposed host is presumed to cause scleritis. Recently, mesenchymal stem cells were reported to have abilities and functions in immunomodulation,43–45
and we propose that SSPCs may play an important role in the development of scleritis. Identification of a multipotent stem cell in the sclera is an important first step in developing future cell-based studies and/or treatments for myopia, scleritis and other scleral disease.
We present a concept that the mouse sclera contains a unique group of multipotent mesenchymal stem cells. This finding may provide a tool to help clarify mechanisms of ocular development and disease and will allow us to investigate the possible role of this group of cells in further studies.