Gago Nuria, Pérez-López Virginia, Sanz-Jaka Juan Pablo, Cormenzana Pedro, Eizaguirre Iñaki, Bernad Antonio, Izeta Ander
Rare Disease Program, Skin Regeneration Laboratory, Fundación Inbiomed, Paseo Mikeletegi 61, San Sebastián, Spain.
Stem Cells. 2009 May;27(5):1164-72. doi: 10.1002/stem.27.
A major unanswered question in autologous cell therapy is the appropriate timing for cell isolation. Many of the putative target diseases arise with old age and previous evidence, mainly from animal models, suggests that the stem/progenitor cell pool decreases steadily with age. Studies with human cells have been generally hampered to date by poor sample availability. In recent years, several laboratories have reported on the existence, both in rodents and humans, of skin-derived precursor (SKP) cells with the capacity to generate neural and mesodermal progenies. This easily obtainable multipotent cell population has raised expectations for their potential use in cell therapy of neurodegeneration. However, we still lack a clear understanding of the spatiotemporal abundance and phenotype of human SKPs. Here we show an analysis of human SKP abundance and in vitro differentiation potential, by using SKPs isolated from four distinct anatomic sites (abdomen, breast, foreskin, and scalp) from 102 healthy subjects aged 8 months to 85 years. Human SKP abundance and differentiation potential decrease sharply with age, being extremely difficult to isolate, expand, and differentiate when obtained from the elderly. Our data suggest preserving human SKP cell banks early in life would be desirable for use in clinical protocols in the aging population.
自体细胞治疗中一个尚未得到解答的主要问题是细胞分离的合适时机。许多假定的目标疾病都与衰老有关,而且先前主要来自动物模型的证据表明,干细胞/祖细胞库会随着年龄的增长而稳步减少。迄今为止,由于样本获取困难,有关人类细胞的研究普遍受到阻碍。近年来,几个实验室报告称,在啮齿动物和人类中都存在具有产生神经和中胚层后代能力的皮肤衍生前体细胞(SKP)。这种易于获取的多能细胞群体让人们对其在神经退行性疾病细胞治疗中的潜在应用充满期待。然而,我们对人类SKP的时空丰度和表型仍缺乏清晰的认识。在这里,我们通过使用从102名年龄在8个月至85岁的健康受试者的四个不同解剖部位(腹部、乳房、包皮和头皮)分离出的SKP,对人类SKP的丰度和体外分化潜能进行了分析。人类SKP的丰度和分化潜能会随着年龄的增长而急剧下降,从老年人身上获取的SKP极难分离、扩增和分化。我们的数据表明,为老年人群的临床方案保存人类SKP细胞库宜尽早进行。