Participation of Somatic Stem Cells, Recognized by a Unique A3 Antibody, in Mucosal Epithelial Regeneration in Dextran Sulfate Sodium (DSS)–Induced Rat Colonic Lesions

Abstract

A3, generated as a monoclonal antibody against rat malignant fibrous histiocytoma cells, recognizes somatic stem cells in rats. We analyzed the distribution of A3-positive cells in dextran sulfate sodium (DSS)–induced colonic lesions consisting of regenerating mucosa and fibrosis. Male 6-week-old F344 rats were administered 5% DSS in drinking water for 5 to 7 days, and lesions at recovery stage were also examined. In untreated control adult colons, A3-positive cells are localized around the crypts where stem cell niche is formed. Histopathologically, in colons of DSS-administered rats, mucosal atrophy, inflammatory cell infiltration, and fibrosis were observed in the lamina propria; thereafter, mucosal epithelia were desquamated, and crypts were decreased gradually with decrease in surrounding A3-positive cells. At the early recovery stage, crypts showed regeneration with reappearance of A3-positive cells. Interestingly, A3-positive cells aggregated in desquamated mucosa surface of fibrosis. Aggregated A3-positive cells coexpressed with vimentin, Thy-1, and partly CK19 but did not react simultaneously with α-SMA. Likely, aggregated A3-positive cells may be rescue cells with nature of both mesenchymal and epithelial cells to maintain self-renewal after injury in the colon. A3 antibody would become a useful tool to investigate the participation of stem cells in rat colonic lesions.

Participation of Somatic Stem Cells, Labeled by a Unique Antibody (A3) Recognizing Both N-glycan and Peptide, to Hair Follicle Cycle and Cutaneous Wound Healing in Rats

“…The differences in nature of mesenchymal immature cells and epitopes recognized by these antibodies should be investigated further. Interestingly, A3 labeled endothelial cells not only in the bone marrow but, also, in neovascularity such as in granulation tissues in wound healing and in regenerating tissues in colitis [20]. It has been reported that human embryonic stem cells (ES cells) and induced pluripotent stem cells (iPS cells) show direct differentiation to endothelial cells [21,22].…”

“…When the epidermis is disturbed (such as wound), hair follicle-constituting cells contribute to wound regeneration (particularly, re-epithelialization) [29]. In addition, it was reported that A3-positive cells contributed to the tissue regeneration in rat colonic lesions, of which the situation was regarded as a stem cell niche [20]. In colonic lesions, A3-positive cells aggregated beneath the desquamated mucosa, where the re-epithelialization occurred nearby, and the cells reacted simultaneously to CD90, vimentin and CK19 [20].…”

“…In addition, it was reported that A3-positive cells contributed to the tissue regeneration in rat colonic lesions, of which the situation was regarded as a stem cell niche [20]. In colonic lesions, A3-positive cells aggregated beneath the desquamated mucosa, where the re-epithelialization occurred nearby, and the cells reacted simultaneously to CD90, vimentin and CK19 [20]. In this study, the signal intensities to preexisting immature cell markers (as mentioned above) in the hair follicle at the edge of the wound bed were upregulated, as compared with those in the control skin; these positive cells in the present wound healing were corresponding partly to A3-positive cells.…”

Stem cell pathology: histogenesis of malignant fibrous histiocytoma and characterization of myofibroblasts appearing in fibrotic lesions

“…Mesenchymal nestin-positive cells are regarded as stem cells with neural and mesoderm differentiation potentials [ 3 ]. In addition, A3-labeled cells contribute to the tissue regeneration in rat colonic lesions, indicating that they may take part in the stem cell niche for the formation of mucosal epithelial cells [ 61 ]. A3-labeled cells seem to act as rescue cells after injury in colon ulcer [ 61 ].…”

“…In addition, A3-labeled cells contribute to the tissue regeneration in rat colonic lesions, indicating that they may take part in the stem cell niche for the formation of mucosal epithelial cells [ 61 ]. A3-labeled cells seem to act as rescue cells after injury in colon ulcer [ 61 ]. The rescue cells have nature of both mesenchymal and epithelial cells to maintain self-renewal, keeping the barrier from external environment under progress of re-epithelialization after injury.…”