Tevlin Ruth, Longaker Michael T, Wan Derrick C
Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, United States.
Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Stanford University School of Medicine, Stanford, CA, United States.
Front Dent Med. 2020 Nov;1. doi: 10.3389/fdmed.2020.596706. Epub 2020 Nov 23.
Defects of the craniofacial skeleton arise as a direct result of trauma, diseases, oncological resection, or congenital anomalies. Current treatment options are limited, highlighting the importance for developing new strategies to restore form, function, and aesthetics of missing or damaged bone in the face and the cranium. For optimal reconstruction, the goal is to replace "like with like." With the inherent challenges of existing options, there is a clear need to develop alternative strategies to reconstruct the craniofacial skeleton. The success of mesenchymal stem cell-based approaches has been hampered by high heterogeneity of transplanted cell populations with inconsistent preclinical and clinical trial outcomes. Here, we discuss the novel characterization and isolation of mouse skeletal stem cell (SSC) populations and their response to injury, systemic disease, and how their re-activation can contribute to tissue regeneration. These studies led to the characterization of human SSCs which are able to self-renew, give rise to increasingly fate restricted progenitors, and differentiate into bone, cartilage, and bone marrow stroma, all on the clonal level without prior culture. SSCs hold great potential for implementation in craniofacial bone tissue engineering and regenerative medicine. As we begin to better understand the diversity and the nature of skeletal stem and progenitor cells, there is a tangible future whereby a subset of human adult SSCs can be readily purified from bone or activated with broad potential applications in craniofacial tissue engineering.
颅面骨骼缺陷是由创伤、疾病、肿瘤切除或先天性异常直接导致的。目前的治疗选择有限，这凸显了开发新策略以恢复面部和颅骨中缺失或受损骨骼的形态、功能和美观的重要性。为了实现最佳重建，目标是“以相似物替代相似物”。鉴于现有选择存在内在挑战，显然需要开发替代策略来重建颅面骨骼。基于间充质干细胞的方法的成功受到移植细胞群体高度异质性的阻碍，临床前和临床试验结果不一致。在此，我们讨论小鼠骨骼干细胞（SSC）群体的新特性和分离方法，以及它们对损伤、全身性疾病的反应，以及它们的重新激活如何促进组织再生。这些研究促成了对人类SSC的特性描述，这些细胞能够自我更新，产生命运限制越来越严格的祖细胞，并在克隆水平上分化为骨、软骨和骨髓基质，无需预先培养。SSC在颅面骨组织工程和再生医学中具有巨大的应用潜力。随着我们开始更好地理解骨骼干细胞和祖细胞的多样性和本质，未来有望从骨骼中轻松纯化出一部分人类成年SSC，或激活它们，从而在颅面组织工程中具有广泛的潜在应用。
