由细胞自聚集形成的用于周围神经再生的功能性组织工程微组织。
Functional tissue-engineered microtissue formed by self-aggregation of cells for peripheral nerve regeneration.
机构信息
Institute of Orthopedics, First Medical Center of the Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Lab of Musculoskeletal Trauma and War Injuries, PLA, No. 28 Fuxing Road, Beijing, 100853, People's Republic of China.
Department of Spine Surgery, Peking University People's Hospital, No.11 Xizhimen South Street, Xicheng District, Beijing, 100044, People's Republic of China.
出版信息
Stem Cell Res Ther. 2022 Jan 10;13(1):3. doi: 10.1186/s13287-021-02676-0.
BACKGROUND
Peripheral nerve injury (PNI) is one of the essential causes of physical disability with a high incidence rate. The traditional tissue engineering strategy, Top-Down strategy, has some limitations. A new tissue-engineered strategy, Bottom-Up strategy (tissue-engineered microtissue strategy), has emerged and made significant research progress in recent years. However, to the best of our knowledge, microtissues are rarely used in neural tissue engineering; thus, we intended to use microtissues to repair PNI.
METHODS
We used a low-adhesion cell culture plate to construct adipose-derived mesenchymal stem cells (ASCs) into microtissues in vitro, explored the physicochemical properties and microtissues components, compared the expression of cytokines related to nerve regeneration between microtissues and the same amount of two-dimension (2D)-cultured cells, co-cultured directly microtissues with dorsal root ganglion (DRG) or Schwann cells (SCs) to observe the interaction between them using immunocytochemistry, quantitative reverse transcription polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA). We used grafts constructed by microtissues and polycaprolactone (PCL) nerve conduit to repair sciatic nerve defects in rats.
RESULTS
The present study results indicated that compared with the same number of 2D-cultured cells, microtissue could secrete more nerve regeneration related cytokines to promote SCs proliferation and axons growth. Moreover, in the direct co-culture system of microtissue and DRG or SCs, axons of DRG grown in the direction of microtissue, and there seems to be a cytoplasmic exchange between SCs and ASCs around microtissue. Furthermore, microtissues could repair sciatic nerve defects in rat models more effectively than traditional 2D-cultured ASCs.
CONCLUSION
Tissue-engineered microtissue is an effective strategy for stem cell culture and therapy in nerve tissue engineering.
背景
周围神经损伤（PNI）是导致身体残疾的主要原因之一，发病率较高。传统的组织工程策略——自上而下策略存在一些局限性。一种新的组织工程策略——自下而上策略（组织工程微组织策略）近年来已经取得了显著的研究进展。然而，据我们所知，微组织在神经组织工程中很少使用；因此，我们意图使用微组织来修复 PNI。
方法
我们使用低黏附细胞培养板将脂肪间充质干细胞（ASCs）在体外构建成微组织，探索其理化性质和微组织成分，比较微组织与同等数量的二维（2D）培养细胞之间与神经再生相关的细胞因子表达，直接将微组织与背根神经节（DRG）或雪旺细胞（SCs）共培养，通过免疫细胞化学、定量逆转录聚合酶链反应（qRT-PCR）、酶联免疫吸附试验（ELISA）观察它们之间的相互作用。我们使用微组织和聚己内酯（PCL）神经导管构建的移植物修复大鼠坐骨神经缺损。
结果
本研究结果表明，与同等数量的 2D 培养细胞相比，微组织能分泌更多促进 SC 增殖和轴突生长的神经再生相关细胞因子。此外，在微组织与 DRG 或 SC 的直接共培养系统中，DRG 的轴突沿微组织的方向生长，并且在微组织周围似乎有 SC 和 ASC 之间的细胞质交换。此外，微组织在修复大鼠坐骨神经缺损方面比传统的 2D 培养 ASC 更有效。
结论
组织工程微组织是一种有效的干细胞培养和神经组织工程治疗策略。
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