(A, B) Transplantation model with different combinations of syngeneic (white) and mismatched (black) HSCs and BMSCs co-transplanted into BALB/c mice. (B, i–v) (i) Negative control, (ii) mismatched BMSC transplantation, (iii) syngeneic BMSC transplantation, (iv) positive control, and (v) mismatched MSC-depleted WBMT. Excessive fibrosis (deep blue, and ∗) in various organs was observed in mismatched BMSC transplanted mice after 3 weeks. Double arrows indicate epidermal and dermal thickness. The fibrotic areas were assessed as the ratio of the blue-stained area per field. D, duct. Minimal Mallory staining areas (▲) in (iii) and (v) are physiological changes and necessary to support the structure of ducts and intestinal walls. Scale bar, 100 μm (50 μm in liver). (C) HSP47+ fibroblasts in the lacrimal glands were significantly higher following mismatched BMSC transplantation (red) compared to syngeneic BMSC (blue), and BMSC-depleted WBM transplantation (green). The number of HSP47+ cells in negative control (i) (blue), and syngeneic MSC transplantation (iii) (blue), and mismatched MSC transplantation (ii) (red), and positive control (iv) (red), and mismatched MSC-depleted WBMT (green). Data are shown as mean ± SD, #p<0.05, *p<0.01, **p<0.001. (D) Tear volume in the same groups described in (C). Data are shown as mean ± SD, n = 2-5 per group, *p<0.05. (E, F) The degree of fibrosis (blue) in the lacrimal glands of mismatched BMSC recipients was dose dependent. Excessive fibrotic areas are shown in deep blue (∗). Data are shown as mean ± SD, n = 3. Scale bar, 100 μm. *p<0.001. BMSCs, bone marrow stromal/stem cells; HSCs, hematopoietic stem cells; SD, standard deviation.