Yun Byeong Gon, Lee Se-Hwan, Jeon Jung Ho, Kim Seok-Won, Jung Chan Kwon, Park Gyeongsin, Kim Su Young, Jeon Sora, Lee Min Suk, Park Sun Hwa, Jang Jinah, Yang Hee Seok, Cho Dong-Woo, Lim Jung Yeon, Kim Sung Won
Department of Otolaryngology-Head and Neck Surgery, Seoul St. Mary's Hospital, The Catholic University of Korea, 222 Banpo-Daero, Seocho-gu, Seoul 06591, Republic of Korea.
Department of Creative IT Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam ro, Nam-gu, Pohang, Kyungbuk 790-784, Republic of Korea.
ACS Biomater Sci Eng. 2019 Nov 11;5(11):6171-6185. doi: 10.1021/acsbiomaterials.9b01356. Epub 2019 Oct 31.
Stem cell transplantation is a promising therapeutic strategy that includes both cell therapy and tissue engineering for the treatment of many regenerative diseases; however, the efficacy and safety of stem cell therapy depend on the cell type used in therapeutic and translational applications. In this study, we validated the hypothesis that human nasal turbinate-derived mesenchymal stem cells (hTMSCs) are a potential therapeutic source of adult stem cells for clinical use in bone tissue engineering using three-dimensional (3D) cell-printing technology. hTMSCs were cultured and evaluated for clinical use according to their cell growth, cell size, and preclinical safety and were then incorporated into a multicompositional 3D bioprinting system and investigated for bone tissue regeneration in vitro and in vivo. Finally, hTMSCs were compared with human bone marrow-derived MSCs (hBMSCs), which are the most common stem cell type used in regenerative medicine. hTMSCs from three different donors showed greater and faster cell growth than hBMSCs from two different donors when cultured. The hTMSCs were smaller in size than the hBMSCs. Furthermore, the hTMSCs did not exhibit safety issues in immunodeficient mice. hTMSCs in 3D-printed constructs (3D-hTMSC) showed much greater viability, growth, and osteogenic differentiation potential in vitro than hBMSCs in 3D-printed constructs (3D-hBMSC). Likewise, 3D-hTMSC showed better cell survival and alkaline phosphatase activity and greater osteogenic protein expression than 3D-hBMSC upon subcutaneous implantation into the dorsal region of nude mice. Notably, in an orthotopic model involving implantation into a tibial defect in rats, implantation of 3D-hTMSC led to greater bone matrix formation and enhanced bone healing to a greater degree than implantation of 3D-hBMSC. The clinically reliable evidence provided by these results is underlined by the potential for rapid tissue regeneration and ambulation in bone fracture patients implanted with 3D-hTMSC.
干细胞移植是一种很有前景的治疗策略，包括细胞治疗和组织工程，用于治疗多种再生性疾病；然而，干细胞治疗的疗效和安全性取决于治疗和转化应用中所使用的细胞类型。在本研究中，我们验证了以下假设：人鼻甲来源的间充质干细胞（hTMSC）是一种潜在的成体干细胞治疗来源，可用于采用三维（3D）细胞打印技术的骨组织工程临床应用。培养hTMSC并根据其细胞生长、细胞大小以及临床前安全性对其进行临床应用评估，然后将其整合到多成分3D生物打印系统中，并在体外和体内研究其骨组织再生情况。最后，将hTMSC与人骨髓来源的间充质干细胞（hBMSC）进行比较，hBMSC是再生医学中最常用的干细胞类型。来自三个不同供体的hTMSC在培养时比来自两个不同供体的hBMSC表现出更大且更快的细胞生长。hTMSC的尺寸比hBMSC小。此外，hTMSC在免疫缺陷小鼠中未表现出安全问题。3D打印构建体中的hTMSC（3D-hTMSC）在体外比3D打印构建体中的hBMSC（3D-hBMSC）表现出更高的活力、生长和骨生成分化潜力。同样，皮下植入裸鼠背部区域后，3D-hTMSC比3D-hBMSC表现出更好的细胞存活和碱性磷酸酶活性以及更高的骨生成蛋白表达。值得注意的是，在涉及植入大鼠胫骨缺损的原位模型中，植入3D-hTMSC比植入3D-hBMSC导致更大程度的骨基质形成和更强的骨愈合。这些结果提供的临床可靠证据凸显了植入3D-hTMSC的骨折患者实现快速组织再生和行走的潜力。
