Fibromodulin reprogrammed cells: A novel cell source for bone regeneration.
Fibromodulin reprogrammed cells: A novel cell source for bone regeneration.
复制标题
DOI：
10.1016/j.biomaterials.2016.01.013
复制
发表时间：
2016-03
期刊：
影响因子：
14
通讯作者：
Soo C
中科院分区：
文献类型：
--
作者：
Li CS;Yang P;Ting K;Aghaloo T;Lee S;Zhang Y;Khalilinejad K;Murphy MC;Pan HC;Zhang X;Wu B;Zhou YH;Zhao Z;Zheng Z;Soo C
由于局部内源性祖细胞通常不足以恢复组织的连续性或功能，因此多能或多能细胞为基础的治疗对于不可愈合的临界大小的缺损区的骨骼重建至关重要。然而，目前可用的基于细胞的再生策略受到许多障碍的阻碍，包括细胞可获得性不足、痛苦和侵入性的细胞采集过程以及肿瘤形成。此前，我们建立了一种新的平台技术，仅使用单个细胞外蛋白多糖-纤维调素(FMOD)来诱导静止的干细胞样阶段，从而绕过基因转导。在这项研究中，我们进一步纯化并显著提高了产量多潜能FMOD重编程(FReP)细胞的重编程速率。我们还通过基因图谱揭示了FReP细胞成骨分化的分子蓝图。放射学分析表明，将FReP细胞移植到临界大小的SCID小鼠颅骨缺损中，有助于FReP细胞在具有挑战性的临床相关创伤场景中在体内具有强大的成骨能力。组织学和免疫组织化学染色证实移植的FReP细胞在体内持续、植入和成骨。综上所述，我们已经提供了基于FReP细胞的骨再生的扩展的有效性、安全性和分子图谱。因此，FReP细胞在骨再生的细胞和基因治疗产品方面具有很高的潜力。
Pluripotent or multipotent cell-based therapeutics are vital for skeletal reconstruction in non-healing critical-sized defects since the local endogenous progenitor cells are not often adequate to restore tissue continuity or function. However, currently available cell-based regenerative strategies are hindered by numerous obstacles including inadequate cell availability, painful and invasive cell-harvesting procedures, and tumorigenesis. Previously, we established a novel platform technology for inducing a quiescent stem cell-like stage using only a single extracellular proteoglycan, fibromodulin (FMOD), circumventing gene transduction. In this study, we further purified and significantly increased the reprogramming rate of the yield multipotent FMOD reprogrammed (FReP) cells. We also exposed the ‘molecular blueprint’ of FReP cell osteogenic differentiation by gene profiling. Radiographic analysis showed that implantation of FReP cells into a critical-sized SCID mouse calvarial defect, contributed to the robust osteogenic capability of FReP cells in a challenging clinically relevant traumatic scenario in vivo. The persistence, engraftment, and osteogenesis of transplanted FReP cells without tumorigenesis in vivo were confirmed by histological and immunohistochemical staining. Taken together, we have provided an extended potency, safety, and molecular profile of FReP cell-based bone regeneration. Therefore, FReP cells present a high potential for cellular and gene therapy products for bone regeneration.