Cell and Tissue Engineering Laboratory, IRCCS Galeazzi Orthopaedic Institute, Via R. Galeazzi 4, 20161 Milan,
Eur Cell Mater. 2014 Apr 23;27:298-311. doi: 10.22203/ecm.v027a21.
Cell-based therapies have recently been proposed for the treatment of degenerative articular pathologies, such as early osteoarthritis, with an emphasis on autologous mesenchymal stem cells (MSCs), as an alternative to terminally differentiated cells. In this study, we performed a donor-matched comparison between infrapatellar fat pad MSCs (IFP-MSCs) and knee subcutaneous adipose tissue stem cells (ASCs), as appealing candidates for cell-based therapies that are easily accessible during surgery. IFP-MSCs and ASCs were obtained from 25 osteoarthritic patients undergoing total knee replacement and compared for their immunophenotype and differentiative potential. Undifferentiated IFP-MSCs and ASCs displayed the same immunophenotype, typical of MSCs (CD13+/CD29+/CD44+/CD73+/CD90+/CD105+/CD166+/CD31-/CD45-). IFP-MSCs and ASCs showed similar adipogenic potential, though undifferentiated ASCs had higher LEP expression compared to IFP-MSCs (p<0.01). Higher levels of calcified matrix (p<0.05) and alkaline phosphatase (p<0.05) in ASCs highlighted their superior osteogenic commitment compared to IFP-MSCs. Conversely, IFP-MSCs pellets showed greater amounts of glycosaminoglycans (p<0.01) and superior expression of ACAN (p<0.001), SOX9, COMP (p<0.001) and COL2A1 (p<0.05) compared to ASCs pellets, revealing a superior chondrogenic potential. This was also supported by lower COL10A1 (p<0.05) and COL1A1 (p<0.01) expression and lower alkaline phosphatase release (p<0.05) by IFP-MSCs compared to ASCs. The observed dissimilarities between IFP-MSCs and ASCs show that, despite expressing similar surface markers, MSCs deriving from different fat depots in the same surgical site possess specific features. Furthermore, the in vitro peculiar commitment of IFP-MSCs and ASCs from osteoarthritic donors towards the chondrogenic or osteogenic lineage may suggest a preferential use for cartilage and bone cell-based treatments, respectively.
细胞疗法最近被提议用于治疗退行性关节病变，如早期骨关节炎，强调使用自体间充质干细胞（MSCs）作为终末分化细胞的替代物。在这项研究中，我们对髌下脂肪垫间充质干细胞（IFP-MSCs）和膝关节皮下脂肪组织干细胞（ASCs）进行了供体匹配比较，这两种细胞都是手术中容易获得的细胞治疗有吸引力的候选细胞。从 25 名接受全膝关节置换术的骨关节炎患者中获得 IFP-MSCs 和 ASCs，并比较其免疫表型和分化潜能。未分化的 IFP-MSCs 和 ASCs 表现出相同的免疫表型，为典型的间充质干细胞（CD13+/CD29+/CD44+/CD73+/CD90+/CD105+/CD166+/CD31-/CD45-）。IFP-MSCs 和 ASCs 具有相似的成脂潜能，尽管未分化的 ASCs 的 LEP 表达高于 IFP-MSCs（p<0.01）。ASCs 中更高水平的钙化基质（p<0.05）和碱性磷酸酶（p<0.05）突出了其与 IFP-MSCs 相比具有更高的成骨能力。相反，IFP-MSCs 球状体表现出更多的糖胺聚糖（p<0.01）和更高的 ACAN（p<0.001）、SOX9、COMP（p<0.001）和 COL2A1（p<0.05）的表达，与 ASCs 球状体相比，显示出更高的软骨形成潜力。IFP-MSCs 与 ASCs 之间的这种差异表明，尽管表达相似的表面标志物，但来自同一手术部位不同脂肪沉积的 MSC 具有特定的特征。此外，来自骨关节炎供体的 IFP-MSCs 和 ASCs 在体外向软骨或成骨谱系的特殊分化能力可能表明，它们分别更适合软骨和骨细胞治疗。
