Bone Marrow‐Derived Cells Implanted into Freeze‐Injured Urinary Bladders Reconstruct Functional Smooth Muscle Layers
Bone Marrow‐Derived Cells Implanted into Freeze‐Injured Urinary Bladders Reconstruct Functional Smooth Muscle Layers
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DOI：
10.1111/j.1757-5672.2010.00066.x
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发表时间：
2010-04
期刊：
影响因子：
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通讯作者：
Tetsuya Imamura;O. Ishizuka;Tokunori Yamamoto;M. Gotoh;O. Nishizawa
中科院分区：
文献类型：
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作者：
Tetsuya Imamura;O. Ishizuka;Tokunori Yamamoto;M. Gotoh;O. Nishizawa
再生医学为因膀胱和尿道不可逆损伤而导致的下尿路功能障碍带来了巨大希望。我们的目标是利用骨髓来源的细胞重建平滑肌层，以治疗不可逆损伤的下尿路。在我们的膀胱再生小鼠模型系统中，约三分之一膀胱的大部分平滑肌层因短暂冷冻而被破坏。受伤三天后，我们植入来自骨髓的培养细胞。植入的骨髓源性细胞存活并分化成分层平滑肌结构，可修复泌尿功能障碍。然而，植入完整的正常膀胱的骨髓来源的细胞不会表现出这些行为。冻伤膀胱壁上存在的大孔可能有助于植入细胞的高存活率。这些孔还可以充当重建组织结构的支架。存活的宿主细胞上调多种生长因子 mRNA，这些生长因子 mRNA 如果被翻译，可以促进平滑肌和其他细胞类型的分化。我们的结论是，骨髓来源细胞的多能性以及微环境提供的支架和合适的生长因子使得我们的膀胱再生模型系统中的组织工程能够成功。在这篇综述中，我们认为再生医学的发展不仅需要更好地了解未分化细胞增殖和靶向分化的要求，还需要进一步了解受体组织内每种独特的微环境。
Regenerative medicine offers great hope for lower urinary tract dysfunctions due to irreversibly damaged urinary bladders and urethras. Our aim is the utilization of bone marrow‐derived cells to reconstruct smooth muscle layers for the treatments of irreversibly damaged lower urinary tracts. In our mouse model system for urinary bladder regeneration, the majority of smooth muscle layers in about one‐third of the bladder are destroyed by brief freezing. Three days after wounding, we implant cultured cells derived from bone marrow. The implanted bone marrow‐derived cells survive and differentiate into layered smooth muscle structures that remediate urinary dysfunction. However, bone marrow‐derived cells implanted into the intact normal urinary bladders do not exhibit these behaviors. The presence of large pores in the walls of the freeze‐injured urinary bladders is likely to be helpful for a high rate of survival of the implanted cells. The pores could also serve as scaffolding for the reconstruction of tissue structures. The surviving host cells upregulate several growth factor mRNAs that, if translated, can promote differentiation of smooth muscle and other cell types. We conclude that the multipotency of the bone marrow‐derived cells and the provision of scaffolding and suitable growth factors by the microenvironment enable successful tissue engineering in our model system for urinary bladder regeneration. In this review, we suggest that the development of regenerative medicine needs not only a greater understanding of the requirements for undifferentiated cell proliferation and targeted differentiation, but also further knowledge of each unique microenvironment within recipient tissues.