Vascularized Composite Allotransplantation (VCA) Research Laboratory, Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Division of Plastic and Reconstructive Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
Vascularized Composite Allotransplantation (VCA) Research Laboratory, Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Center for Vascularized Composite Allotransplantation, Department of Plastic Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Transpl Immunol. 2014 May;30(4):122-7. doi: 10.1016/j.trim.2014.03.001. Epub 2014 Mar 12.
Age negatively impacts the biologic features of mesenchymal stem cells (MSCs), including decreased expansion kinetics and differentiation potential. Clinically, donor-age may be within a wide spectrum; therefore, investigation of the role of donor's age on immunoregulatory potential is of critical importance to translate stem cell therapies from bench to bedside.
Adipose and bone marrow derived MSCs (ASCs and BMSCs) were isolated in parallel from Lewis and Brown Norway rats of young (less than 4-week old) and senior groups (older than 15-month). The presentation of cells and time required for growth to 90% confluence was recorded. FACS sorting based on the expression of CD90 and CD29 double positive and CD45 CD11 double negative quantified the proportions of MSCs. After expansion, ASCs and BMSCs from different age groups were co-cultured in mixed lymphocyte reaction (MLR; Lewis vs. Brown Norway) assays. The suppression of CD3(+)CD4(+) and CD3(+)CD8(+) T cell populations by different sources of MSCs were compared.
The kinetics of cell growth was slower in old animals (17.3±2days) compared with young animals (8.8±3days), and cell morphology was irregular and enlarged in the senior groups. The yield of MSCs by FACS sorting was significantly higher in young groups compared to senior groups (p<0.02). With regard to immunoregulatory potential, senior ASCs failed to induce any CD3(+)CD4(+) T cell suppression (p>0.05). In addition, young BMSCs-induced suppression was more prominent than seniors (p<0.05).
Donor age should be taken into consideration when using recipient MSC of either bone marrow or adipose origin in clinical applications.
年龄会对间充质干细胞（MSCs）的生物学特性产生负面影响，包括扩增动力学和分化潜能的降低。临床上，供体年龄可能存在很大差异；因此，研究供体年龄对免疫调节潜能的作用对于将干细胞疗法从实验室转化到临床至关重要。
从年轻（小于 4 周龄）和老年（大于 15 月龄）的 Lewis 和 Brown Norway 大鼠中平行分离脂肪组织和骨髓来源的间充质干细胞（ASCs 和 BMSCs）。记录细胞的呈现和达到 90%汇合所需的时间。基于 CD90 和 CD29 双阳性和 CD45 CD11 双阴性的表达进行 FACS 分选，定量了 MSCs 的比例。扩增后，来自不同年龄组的 ASC 和 BMSC 在混合淋巴细胞反应（MLR；Lewis 对 Brown Norway）测定中进行共培养。比较不同来源的 MSC 对 CD3(+)CD4(+)和 CD3(+)CD8(+)T 细胞群的抑制作用。
与年轻动物（8.8±3 天）相比，老年动物（17.3±2 天）的细胞生长动力学较慢，且老年组的细胞形态不规则且增大。FACS 分选的 MSC 产量在年轻组明显高于老年组（p<0.02）。就免疫调节潜能而言，老年 ASC 未能诱导任何 CD3(+)CD4(+)T 细胞抑制（p>0.05）。此外，年轻 BMSC 诱导的抑制作用比老年组更明显（p<0.05）。
在临床应用中，无论是骨髓来源还是脂肪来源的 MSC，都应考虑供体年龄因素。
