Induction of smooth muscle cell-like phenotype in marrow-derived cells among regenerating urinary bladder smooth muscle cells
Induction of smooth muscle cell-like phenotype in marrow-derived cells among regenerating urinary bladder smooth muscle cells
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DOI：
10.1016/s0002-9440(10)62278-x
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发表时间：
2005-02-01
影响因子：
6
通讯作者：
Ogawa, O
中科院分区：
文献类型：
--
作者：
Kanematsu, A;Yamamoto, S;Ogawa, O
脱细胞基质移植物上的组织再生在治疗性器官重建中具有巨大的潜力。然而，中空器官如膀胱需要平滑肌细胞再生，其机制尚未明确。我们研究了骨髓细胞参与膀胱再生过程中平滑肌形成的机制，使用体内和体外模型系统。将体内表达绿色荧光蛋白的骨髓细胞移植到致死辐射的大鼠中。移植8周后，用膀胱脱细胞基质移植物替代大鼠膀胱穹隆。术后两周，移植的骨髓细胞重新填充移植物，如通过检测荧光染色所证明的。到12周时，他们重建了平滑肌层，天然平滑肌细胞（SMC）浸润移植物。在体外培养条件下，研究了膀胱尿路上皮细胞和膀胱平滑肌细胞所形成的不同生长因子环境对骨髓细胞表型变化的不同影响。首先，将培养的膀胱细胞的上清液用作骨髓细胞的条件培养基。第二，这些条件用外源性生长因子重建。在每种情况下，SMC特有生长因子环境诱导骨髓细胞中的SMC样表型，而尿路上皮细胞则失败。这些结果表明，骨髓细胞分化成平滑肌细胞的无细胞基质移植物在SMC所创造的环境。
Tissue regeneration on acellular matrix grafts has great potential for therapeutic organ reconstruction. However, hollow organs such as the bladder require smooth muscle cell regeneration, the mechanisms of which are not well defined. We investigated the mechanisms by which bone marrow cells participate in smooth muscle formation during urinary bladder regeneration, using in vivo and in vitro model systems. In vivo bone marrow cells expressing green fluorescent protein were transplanted into lethally irradiated rats. Eight weeks following transplantation, bladder domes of the rats were replaced with bladder acellular matrix grafts. Two weeks after operation transplanted marrow cells repopulated the graft, as evidenced by detection of fluorescent staining. By 12 weeks they reconstituted the smooth muscle layer, with native smooth muscle cells (SMC) infiltrating the graft. lit vitro, the differential effects of distinct growth factor environments created by either bladder urothelial cells or bladder SMC on phenotypic changes of marrow cells were examined. First, supernatants of cultured bladder cells were used as conditioned media for marrow cells. Second, these conditions were reconstituted with exogenous growth factors. in each case, a growth factor milieu characteristic of SMC induced an SMC-like phenotype in marrow cells, whereas that of urothelial cells failed. These findings suggest that marrow cells differentiate into smooth muscle on acellular matrix grafts in response to the environment created by SMC.