Department of Orthopaedic Surgery, Keck School of Medicine of the University of Southern California, 2011 Zonal Ave,HMR 702, Los Angeles, CA, 90089, USA.
Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA, USA.
Gene Ther. 2023 Apr;30(3-4):369-376. doi: 10.1038/s41434-022-00367-w. Epub 2022 Oct 11.
Human adipose-derived mesenchymal stem cells (ASCs) transduced with a lentiviral vector system to express bone morphogenetic protein 2 (LV-BMP-2) have been shown to reliably heal bone defects in animal models. However, the influence of donor characteristics such as age, sex, race, and medical co-morbidities on ASC yield, growth and bone regenerative capacity, while critical to the successful clinical translation of stem cell-based therapies, are not well understood. Human ASCs isolated from the infrapatellar fat pads in 122 ASC donors were evaluated for cell growth characteristics; 44 underwent additional analyses to evaluate in vitro osteogenic potential, with and without LV-BMP-2 transduction. We found that while female donors demonstrated significantly higher cell yield and ASC growth rates, age, race, and the presence of co-morbid conditions were not associated with differences in proliferation. Donor demographics or the presence of comorbidities were not associated with differences in in vitro osteogenic potential or stem cell differentiation, except that transduced ASCs from healthy donors produced more BMP-2 at day 2. Overall, donor age, sex, race, and the presence of co-morbid conditions had a limited influence on cell yield, proliferation, self-renewal capacity, and osteogenic potential for non-transduced and transduced (LV-BMP-2) ASCs. These results suggest that ASCs are a promising resource for both autologous and allogeneic cell-based gene therapy applications.
人脂肪间充质干细胞（ASCs）经慢病毒载体系统转染表达骨形态发生蛋白 2（LV-BMP-2），已被证明能可靠地治愈动物模型中的骨缺损。然而，供体特征（如年龄、性别、种族和合并症）对 ASC 产量、生长和骨再生能力的影响，虽然对基于干细胞治疗的成功临床转化至关重要，但尚未得到很好的理解。我们从 122 名 ASC 供体的髌下脂肪垫中分离出 ASC，评估其细胞生长特性；44 名供体进行了额外的分析，以评估有无 LV-BMP-2 转导的体外成骨潜能。我们发现，虽然女性供体表现出更高的细胞产量和 ASC 生长速度，但年龄、种族和合并症的存在与增殖差异无关。供体人口统计学或合并症的存在与体外成骨潜能或干细胞分化无关，除了来自健康供体的转导 ASC 在第 2 天产生更多的 BMP-2 外。总体而言，供体年龄、性别、种族和合并症的存在对未转导和转导（LV-BMP-2）的 ASC 的细胞产量、增殖、自我更新能力和成骨潜能的影响有限。这些结果表明，ASCs 是自体和同种异体基于细胞的基因治疗应用的有前途的资源。
