Cotransplantation with specific populations of spina bifida bone marrow stem/progenitor cells enhances urinary bladder regeneration
Cotransplantation with specific populations of spina bifida bone marrow stem/progenitor cells enhances urinary bladder regeneration
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DOI：
10.1073/pnas.1220764110
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发表时间：
2013-03-05
影响因子：
11.1
通讯作者：
Cheng, Earl Y.
中科院分区：
文献类型：
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作者：
Sharma, Arun K.;Bury, Matthew I.;Cheng, Earl Y.
患有脊髓脊膜膨出的脊柱裂（SB）患者通常具有神经源性膀胱，并表现出不同程度的膀胱功能障碍。虽然肠膀胱成形术形式的外科干预是治疗神经源性膀胱的当前标准，但它仍然是一种权宜之计，并且由于使用肠作为替代组织的来源而与许多并发症相关。当使用自体细胞群时，当代膀胱组织工程策略缺乏改革膀胱平滑肌、脉管系统和促进外周神经组织生长的能力。在本研究的背景下，我们证明了两个特定的骨髓（BM）干细胞/祖细胞群体与合成弹性支架结合使用的作用，该支架为当前的膀胱再生方法提供了独特的替代手段。在体外分化，基因表达和增殖是相似的供体间充质干细胞（MSC），而聚（1，8-辛二醇-共柠檬酸盐）支架接种SB BM MSC执行类似的控制同行在体内膀胱平滑肌壁的形成。与未接种造血干/祖细胞的样本相比，SB CD 34（+）造血干/祖细胞与供体匹配的MSC共移植导致移植区域组织血管化显著增加以及外周神经生长的诱导。最后，MSC/CD 34（+）移植物为尿路上皮的快速再生提供了动力。数据表明，自体骨髓干/祖细胞可用作SB患者特异性膀胱组织再生的替代、非致病性细胞来源，以代替当前的肠膀胱成形术，并对其他膀胱再生疗法产生影响。
Spina bifida (SB) patients afflicted with myelomeningocele typically possess a neurogenic urinary bladder and exhibit varying degrees of bladder dysfunction. Although surgical intervention in the form of enterocystoplasty is the current standard of care in which to remedy the neurogenic bladder, it is still a stop-gap measure and is associated with many complications due to the use of bowel as a source of replacement tissue. Contemporary bladder tissue engineering strategies lack the ability to reform bladder smooth muscle, vasculature, and promote peripheral nerve tissue growth when using autologous populations of cells. Within the context of this study, we demonstrate the role of two specific populations of bone marrow (BM) stem/progenitor cells used in combination with a synthetic elastomeric scaffold that provides a unique and alternative means to current bladder regeneration approaches. In vitro differentiation, gene expression, and proliferation are similar among donor mesenchymal stem cells (MSCs), whereas poly(1,8-octanediol-cocitrate) scaffolds seeded with SB BM MSCs perform analogously to control counterparts with regard to bladder smooth muscle wall formation in vivo. SB CD34(+) hematopoietic stem/progenitor cells cotransplanted with donor-matched MSCs cause a dramatic increase in tissue vascularization as well as an induction of peripheral nerve growth in grafted areas compared with samples not seeded with hematopoietic stem/progenitor cells. Finally, MSC/CD34(+) grafts provided the impetus for rapid urothelium regeneration. Data suggest that autologous BM stem/progenitor cells may be used as alternate, nonpathogenic cell sources for SB patient-specific bladder tissue regeneration in lieu of current enterocystoplasty procedures and have implications for other bladder regenerative therapies.