Clonogenic multipotent stem cells in human adipose tissue differentiate into functional smooth muscle cells
Clonogenic multipotent stem cells in human adipose tissue differentiate into functional smooth muscle cells
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DOI：
10.1073/pnas.0604850103
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发表时间：
2006-08-08
影响因子：
11.1
通讯作者：
Ignarro, Louis J.
中科院分区：
文献类型：
--
作者：
Rodriguez, Larissa V.;Alfonso, Zeni;Ignarro, Louis J.
平滑肌是人体组织的主要组成部分，对包括肠、尿路和血管系统在内的许多器官的正常功能至关重要。干细胞用于基于细胞的组织工程和再生策略代表了平滑肌修复的一个有前途的替代方案。为了使这种策略取得成功，必须确定平滑肌前体细胞的可靠来源。脂肪组织提供了丰富的多能细胞来源。在这项研究中，我们评估了加工过的抽脂（PLA）和脂肪来源的干细胞向表型和功能平滑肌细胞分化的能力。为了诱导分化，将PLA细胞培养在平滑肌分化培养基中。PLA细胞的平滑肌分化诱导了所有平滑肌标记物的遗传表达，并通过平滑肌细胞特异性a - actin （ASMA）、calponin、caldesmon、SM22、myosin重链（MHC）和smoothelin的蛋白表达增加进一步证实。脂肪来源的多能细胞克隆研究表明，这些细胞除了具有三倍分化能力外，还能分化为平滑肌细胞。重要的是，平滑肌分化细胞，而不是它们的前体，在药物作用下表现出收缩和放松的功能能力。总之，脂肪来源的细胞具有分化为功能性平滑肌细胞的潜力，因此，脂肪组织可以成为治疗平滑肌起重要作用的损伤组织的有用细胞来源。
Smooth muscle is a major component of human tissues and is essential for the normal function of a multitude of organs including the intestine, urinary tract and the vascular system. The use of stem cells for cell-based tissue engineering and regeneration strategies represents a promising alternative for smooth muscle repair. For such strategies to succeed, a reliable source of smooth muscle precursor cells must be identified. Adipose tissue provides an abundant source of multipotent cells. In this study, the capacity of processed lipoaspirate (PLA) and adipose-derived stem cells to differentiate into phenotypic and functional smooth muscle cells was evaluated. To induce differentiation, PLA cells were cultured in smooth muscle differentiation medium. Smooth muscle differentiation of PLA cells induced genetic expression of all smooth muscle markers and further confirmed by increased protein expression of smooth muscle cell-specific a actin (ASMA), calponin, caldesmon, SM22, myosin heavy chain (MHC), and smoothelin. Clonal studies of adipose derived multipotent cells demonstrated differentiation of these cells into smooth muscle cells in addition to trilineage differentiation capacity. Importantly, smooth muscle-differentiated cells, but not their precursors, exhibit the functional ability to contract and relax in direct response to pharmacologic agents. In conclusion, adipose-derived cells have the potential to differentiate into functional smooth muscle cells and, thus, adipose tissue can be a useful source of cells for treatment of injured tissues where smooth muscle plays an important role.