Rodríguez Larissa V, Alfonso Zeni, Zhang Rong, Leung Joanne, Wu Benjamin, Ignarro Louis J
Department of Urology, University of California School of Medicine, Los Angeles, CA 90024, USA.
Proc Natl Acad Sci U S A. 2006 Aug 8;103(32):12167-72. doi: 10.1073/pnas.0604850103. Epub 2006 Jul 31.
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 alpha 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.
平滑肌是人体组织的主要组成部分,对于包括肠道、泌尿系统和血管系统在内的众多器官的正常功能至关重要。利用干细胞进行基于细胞的组织工程和再生策略是平滑肌修复的一种有前景的替代方法。要使这些策略成功,必须找到可靠的平滑肌前体细胞来源。脂肪组织提供了丰富的多能细胞来源。在本研究中,评估了处理过的脂肪抽吸物(PLA)和脂肪来源干细胞分化为表型和功能正常的平滑肌细胞的能力。为诱导分化,将PLA细胞在平滑肌分化培养基中培养。PLA细胞的平滑肌分化诱导了所有平滑肌标志物的基因表达,并通过平滑肌细胞特异性α肌动蛋白(ASMA)、钙调蛋白、钙结合蛋白、SM22、肌球蛋白重链(MHC)和平滑肌蛋白的蛋白表达增加得到进一步证实。对脂肪来源的多能细胞的克隆研究表明,这些细胞除了具有三系分化能力外,还能分化为平滑肌细胞。重要的是,平滑肌分化细胞而非其前体细胞,表现出直接对药物作出反应而收缩和舒张的功能能力。总之,脂肪来源的细胞具有分化为功能正常的平滑肌细胞的潜力,因此,脂肪组织可以成为治疗平滑肌起重要作用的受损组织的有用细胞来源。