Tissue Engineering and Regenerative Medicine Laboratory, Columbia University Medical Center, New York, New York 10032, USA.
FASEB J. 2011 Oct;25(10):3496-504. doi: 10.1096/fj.10-176305. Epub 2011 Jul 11.
Cell transplantation has been well explored for cartilage regeneration. We recently showed that the entire articular surface of a synovial joint can regenerate by endogenous cell homing and without cell transplantation. However, the sources of endogenous cells that regenerate articular cartilage remain elusive. Here, we studied whether cytokines not only chemotactically recruit adipose stem cells (ASCs), mesenchymal stem cells (MSCs), and synovium stem cells (SSCs) but also induce chondrogenesis of the recruited cells. Recombinant human transforming growth factor-β3 (TGF-β3; 100 ng) and/or recombinant human stromal derived factor-1β (SDF-1β; 100 ng) was control released into an acellular collagen sponge cube with underlying ASCs, MSCs, or SSCs in monolayer culture. Although all cell types randomly migrated into the acellular collagen sponge cube, TGF-β3 and/or SDF-1β recruited significantly more cells than the cytokine-free control group. In 6 wk, TGF-β3 alone recruited substantial numbers of ASCs (558±65) and MSCs (302±52), whereas codelivery of TGF-β3 and SDF-1β was particularly chemotactic to SSCs (400±120). Proliferation of the recruited cells accounted for some, but far from all, of the observed cellularity. TGF-β3 and SDF-1β codelivery induced significantly higher aggrecan gene expression than the cytokine-free group for ASCs, MSCs, and SSCs. Type II collagen gene expression was also significantly higher for ASCs and SSCs by SDF-1 and TGF-β3 codelivery. Remarkably, the expression of aggrecan and type II collagen was detected among all cell types. Thus, homing of multiple stem/progenitor cell populations may potentially serve as an alternative or adjunctive approach to cell transplantation for cartilage regeneration.
细胞移植在软骨再生中得到了广泛的探索。我们最近发现，滑膜关节的整个关节表面可以通过内源性细胞归巢而无需细胞移植来再生。然而，再生关节软骨的内源性细胞来源仍不清楚。在这里，我们研究了细胞因子是否不仅趋化招募脂肪干细胞（ASCs）、间充质干细胞（MSCs）和滑膜干细胞（SSCs），而且还诱导募集细胞的软骨生成。将重组人转化生长因子-β3（TGF-β3；100ng）和/或重组人基质衍生因子-1β（SDF-1β；100ng）以控制方式释放到单层培养的无细胞胶原海绵立方体中，下面有 ASCs、MSCs 或 SSCs。尽管所有细胞类型都随机迁移到无细胞胶原海绵立方体中，但 TGF-β3 和/或 SDF-1β 募集的细胞数量明显多于无细胞因子对照组。在 6 周时，TGF-β3 单独募集了大量的 ASCs（558±65）和 MSCs（302±52），而 TGF-β3 和 SDF-1β 的共递送对 SSCs 具有特别的趋化性（400±120）。募集细胞的增殖解释了观察到的细胞数量的一部分，但远非全部。与无细胞因子组相比，TGF-β3 和 SDF-1β 的共递送可显著提高 ASCs、MSCs 和 SSCs 的聚集蛋白聚糖基因表达。SDF-1 和 TGF-β3 的共递送也可显著提高 ASCs 和 SSCs 的 II 型胶原基因表达。值得注意的是，在所有细胞类型中均检测到聚集蛋白聚糖和 II 型胶原的表达。因此，多种干细胞/祖细胞群的归巢可能是软骨再生细胞移植的替代或辅助方法。
