Bone marrow derivation of pericryptal myofibroblasts in the mouse and human small intestine and colon

Abstract

Background and aims: In order to establish whether extraintestinal cells contribute to the turnover and repair of gastrointestinal tissues, we studied the colons and small intestines of female mice that had received a male bone marrow transplant, together with gastrointestinal biopsies from female patients that had developed graft versus host disease after receiving a bone marrow transplant from male donors. Methods: Using in situ hybridisation to detect Y chromosomes and immunohistochemistry, we demonstrated that cells derived from injected bone marrow frequently engrafted into the intestine and differentiated into pericryptal myofibroblasts. Results: In the human intestine, we confirmed by combining in situ hybridisation with immunostaining for smooth muscle actin that the bone marrow derived cells within the intestine exhibited a myofibroblast phenotype. In female mouse recipients of male bone marrow grafts, we observed colocalisation of Y chromosomes and clusters of newly formed marrow derived myofibroblasts. While few of these were present at seven days after bone marrow transplantation, they were numerous at 14 days, and by six weeks entire columns of pericryptal myofibroblasts could be seen running up the sides of crypts in both the small intestine and colon. These columns appeared to extend into the villi in the small intestine. Within the intestinal lamina propria, these Y chromosome positive cells were negative for the mouse macrophage marker F4/80 antigen and CD34. Conclusions: Bone marrow derived pericryptal myofibroblasts were present in the mouse intestine following irradiation and bone marrow transplant, and in the intestines of human patients suffering graft versus host disease following a bone marrow transplant. Our data indicate that bone marrow cells contribute to the regeneration of intestinal myofibroblasts and epithelium after damage, and we suggest that this could be exploited therapeutically.

Inflammation, atrophy, and gastric cancer

“…Although studies have focused on well-defined immune cell types, recently it has been recognized that chronic inflammation - in addition to inducing the loss of parietal cells and chief cells in the glandular gastric mucosa - stimulates the recruitment of progenitor cell populations to the stomach and their subsequent engraftment. Numerous reports have demonstrated that chronic inflammation leads to the recruitment of bone marrow-derived endothelial progenitors and bone marrow-derived myofibroblasts in mouse models of colitis and hepatitis (82)(83)(84). Similar cell populations are recruited to the stomach in Helicobacter-induced gastritis (T.C.…”

In Vivo Characterization of Bone Marrow–Derived Fibroblasts Recruited into Fibrotic Lesions

“…For reprints contact: Reprints@AlphaMedPress.com 700 Bone Marrow-Derived Fibroblasts Recruited into Fibrotic Lesions transplantation of bone marrow (BM), hematopoietic stem cells or nonhematopoietic mesenchymal stem cells, muscle [7][8][9][10][11], heart [12][13][14], liver [15][16][17][18][19], vascular cells [20,21], and other mesenchymal cells [22][23][24] of donor origin have been detected. Investigators revealed that BM-derived cells can be progenitors for tissue fibroblasts that are recruited through the circulation to populate peripheral organs [25][26][27][28][29]. During renal fibrosis, a small number of fibroblasts were BM origin using BM chimera and transgenic reporter mice [25].…”

“…We previously reported that cancer-induced stroma generated by the human pancreatic cancer cell line consist of BM-derived fibroblasts and that BM-derived fibroblasts become a major component of cancer-induced stromal cells in the later stage of tumor development [26]. Furthermore, BM-derived fibroblasts were engrafted into multiple organs, and it was found that these cells are recruited into injured tissue [27,28]. However, the phenotype and functional roles of BM-derived fibroblasts have not been fully understood.…”

E-/P-selectins and colon carcinoma metastasis: first in vivo evidence for their crucial role in a clinically relevant model of spontaneous metastasis formation in the lung

“…Endogenous alkaline phosphatase (AP) was blocked with 20% acetic acid in 150 ml methanol for 3 min at room temperature (Brittan et al, 2002). After one further wash in lectin buffer, the sections were incubated for 30 min at room temperature with rabbit normal serum (no.…”