CNRS 5273, UMR STROMALab, Toulouse, France.
Stem Cells Dev. 2011 Dec;20(12):2127-38. doi: 10.1089/scd.2011.0044. Epub 2011 Apr 13.
Adipose-derived stromal cells (ADSCs) are close relatives of bone marrow mesenchymal stromal cells (BM-MSCs). The ease of access to subcutaneous fat pad and the abundance of stromal precursors make fat tissue an attractive source of stromal cells for clinicians. However, their ability to support hematopoietic stem cells in vitro and in vivo has not been established definitively. Thus, their usefulness in supporting hematopoietic stem cell engraftment is not as clear as with BM-MSCs. In this article, we show that human ADSCs, cultured with a good manufacturing practice medium, maintain in vitro human early and committed hematopoietic progenitors and support their complete differentiation toward myeloid and lymphoid lineages. Compared with BM-MSCs, ADSCs elicit a more precocious early progenitor formation and faster proliferation and differentiation of hematopoietic progenitors. Further, in vivo, when co-injected in NOD.Cg-Prkdc(scid) Il2(rgtm1Wjl)/SzJ (NSG) mice with a low number of human CD34(+) cells, ADSCs enabled the higher production of immature human hematopoietic progenitors and CD45(+) cells when compared with BM-MSCs. As a whole, our results indicate that human ADSCs, isolated and expanded under clinical-grade conditions, support hematopoiesis in vitro and in vivo and thus provide the rationale for their use in supporting hematopoietic reconstitution in clinical settings.
脂肪组织来源的基质细胞(ADSCs)与骨髓间充质基质细胞(BM-MSCs)密切相关。由于易于从皮下脂肪垫获取,且基质前体细胞丰富,脂肪组织成为临床医生获取基质细胞的理想来源。然而,其在体外和体内支持造血干细胞的能力尚未得到明确证实。因此,其在支持造血干细胞植入方面的作用不如 BM-MSCs 明确。在本文中,我们表明,经过良好生产规范(GMP)培养基培养的人 ADSCs 可以维持体外人早期和定向造血祖细胞,并支持其向髓系和淋巴系完全分化。与 BM-MSCs 相比,ADSCs 可更早地形成早期祖细胞,并促进造血祖细胞更快地增殖和分化。此外,在体内,当与少量人 CD34+细胞一起注射到 NOD.Cg-Prkdc(scid) Il2(rgtm1Wjl)/SzJ(NSG)小鼠中时,与 BM-MSCs 相比,ADSCs 可促进更多不成熟的人造血祖细胞和 CD45+细胞的产生。总的来说,我们的结果表明,在临床级条件下分离和扩增的人 ADSCs 可在体外和体内支持造血,因此为其在临床环境中支持造血重建的应用提供了依据。