Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery Division, Stanford University School of Medicine, Stanford, CA 94305, USA.
Proc Natl Acad Sci U S A. 2012 Dec 11;109(50):20379-84. doi: 10.1073/pnas.1218052109. Epub 2012 Nov 20.
Pluripotent cells represent a powerful tool for tissue regeneration, but their clinical utility is limited by their propensity to form teratomas. Little is known about their interaction with the surrounding niche following implantation and how this may be applied to promote survival and functional engraftment. In this study, we evaluated the ability of an osteogenic microniche consisting of a hydroxyapatite-coated, bone morphogenetic protein-2-releasing poly-L-lactic acid scaffold placed within the context of a macroenvironmental skeletal defect to guide in vivo differentiation of both embryonic and induced pluripotent stem cells. In this setting, we found de novo bone formation and participation by implanted cells in skeletal regeneration without the formation of a teratoma. This finding suggests that local cues from both the implanted scaffold/cell micro- and surrounding macroniche may act in concert to promote cellular survival and the in vivo acquisition of a terminal cell fate, thereby allowing for functional engraftment of pluripotent cells into regenerating tissue.
多能细胞是组织再生的有力工具，但它们在临床上的应用受到其形成畸胎瘤倾向的限制。目前人们对它们在植入后的周围微环境中的相互作用知之甚少，也不知道如何利用这些相互作用来促进其存活和功能植入。在这项研究中，我们评估了一种成骨微环境的能力，该微环境由一个涂有羟基磷灰石、释放骨形态发生蛋白-2 的聚左旋乳酸支架组成，放置在宏观环境的骨骼缺陷中，以指导胚胎和诱导多能干细胞在体内的分化。在这种情况下，我们发现新形成的骨和植入细胞参与骨骼再生，而没有形成畸胎瘤。这一发现表明，植入的支架/细胞微环境和周围大环境中的局部线索可能协同作用，促进细胞存活和体内获得终末细胞命运，从而允许多能细胞在再生组织中功能性植入。
