Brittan M, Hunt T, Jeffery R, Poulsom R, Forbes S J, Hodivala-Dilke K, Goldman J, Alison M R, Wright N A
Histopathology Unit, Cancer Research UK, London, UK.
Gut. 2002 Jun;50(6):752-7. doi: 10.1136/gut.50.6.752.
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.
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.
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.
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.
为了确定肠外细胞是否有助于胃肠道组织的更新和修复，我们研究了接受雄性骨髓移植的雌性小鼠的结肠和小肠，以及接受来自男性供体的骨髓移植后发生移植物抗宿主病的女性患者的胃肠道活检组织。
通过原位杂交检测Y染色体和免疫组化，我们证明注射的骨髓来源的细胞经常植入肠道并分化为隐窝周围肌成纤维细胞。
在人类肠道中，我们通过将原位杂交与平滑肌肌动蛋白免疫染色相结合证实，肠道内的骨髓来源细胞表现出肌成纤维细胞表型。在接受雄性骨髓移植的雌性小鼠受体中，我们观察到Y染色体与新形成的骨髓来源的肌成纤维细胞簇共定位。虽然这些细胞在骨髓移植后7天很少，但在14天时数量众多，到6周时，在小肠和结肠的隐窝两侧都可以看到完整的隐窝周围肌成纤维细胞柱。这些柱似乎延伸到小肠的绒毛中。在肠固有层内，这些Y染色体阳性细胞对小鼠巨噬细胞标志物F4/80抗原和CD34呈阴性。
照射和骨髓移植后，小鼠肠道中存在骨髓来源的隐窝周围肌成纤维细胞，骨髓移植后发生移植物抗宿主病的人类患者的肠道中也存在。我们的数据表明，骨髓细胞有助于损伤后肠道肌成纤维细胞和上皮的再生，我们认为这可用于治疗。
