Frazier Trivia P, Gimble Jeffrey M, Devay Jessica W, Tucker Hugh A, Chiu Ernest S, Rowan Brian G
Department of Structural and Cellular Biology, Tulane University, New Orleans, LA, USA.
BMC Cell Biol. 2013 Aug 7;14:34. doi: 10.1186/1471-2121-14-34.
Obesity is associated with a higher risk of developing cancer and co-morbidities that are part of the metabolic syndrome. Adipose tissue is recognized as an endocrine organ, as it affects a number of physiological functions, and contains adipose tissue-derived stem cells (ASCs). ASCs can differentiate into cells of multiple lineages, and as such are applicable to tissue engineering and regenerative medicine. Yet the question of whether ASC functionality is affected by the donor's body mass index (BMI) still exists.
ASCs were isolated from patients having different BMIs (BMI-ASCs), within the ranges of 18.5-32.8. It was hypothesized that overweight BMI-ASCs would be more compromised in early adipogenic and osteogenic potential, and ability to form colonies in vitro. BMI was inversely correlated with ASC proliferation and colony forming potential as assessed by CyQUANT proliferation assay (fluorescence- based measurement of cellular DNA content), and colony forming assays. BMI was positively correlated with early time point (day 7) but not later time point (day 15) intracytoplasmic lipid accumulation as assessed by Oil-Red-O staining. Alizarin red staining and RT-PCR for alkaline phosphatase demonstrated that elevated BMI resulted in compromised ASC mineralization of extracellular matrix and decreased alkaline phosphatase mRNA expression.
These data demonstrate that elevated BMI resulted in reduced ASC proliferation, and potentially compromised osteogenic capacity in vitro; thus BMI is an important criterion to consider in selecting ASC donors for clinical applications.
肥胖与患癌症风险增加以及代谢综合征的合并症相关。脂肪组织被认为是一个内分泌器官,因为它影响多种生理功能,并且含有脂肪组织来源的干细胞(ASC)。ASC 可分化为多个谱系的细胞,因此适用于组织工程和再生医学。然而,ASC 的功能是否受供体体重指数(BMI)影响的问题仍然存在。
从 BMI 在 18.5 - 32.8 范围内的不同患者中分离出 ASC(BMI - ASC)。据推测,超重的 BMI - ASC 在早期脂肪生成和成骨潜能以及体外形成集落的能力方面会受到更大损害。通过 CyQUANT 增殖测定法(基于荧光的细胞 DNA 含量测量)和集落形成测定法评估,BMI 与 ASC 增殖和集落形成潜能呈负相关。通过油红 O 染色评估,BMI 与早期时间点(第 7 天)而非后期时间点(第 15 天)的胞浆内脂质积累呈正相关。茜素红染色和碱性磷酸酶的 RT - PCR 表明,BMI 升高导致 ASC 细胞外基质矿化受损以及碱性磷酸酶 mRNA 表达降低。
这些数据表明,BMI 升高导致 ASC 增殖减少,并可能损害其体外成骨能力;因此,BMI 是临床应用中选择 ASC 供体时需要考虑的重要标准。