Section of Tissue Engineering and Stem Cell Therapy, Pediatric Urology and Regenerative Medicine Research Center, Children's Hospital Medical Center, Pediatric Center of Excellence, Tehran University of Medical Sciences, No. 62, Dr. Gharib's Street, Keshavarz Boulevard, Tehran, Iran.
Tracheal Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
J Assist Reprod Genet. 2022 Jun;39(6):1237-1247. doi: 10.1007/s10815-022-02492-2. Epub 2022 May 5.
The aim of this investigation was to design a perfusion-based decellularization protocol to provide whole human uterine bio-scaffolds with preserved structural and componential characteristics and to investigate the in vivo properties of the decellularized tissues.
Eight human uteri, donated by brain-dead patients, were decellularized by perfusion of sodium dodecyl sulfate (SDS) through the uterine arteries using a peristaltic pump. The bio-scaffolds were evaluated and compared with native human uterus regarding histological, immunohistochemical, structural, and bio-mechanical properties, in addition to CT angiographies to examine the preservation of the vascular networks. Subsequently, we obtained acellular patches and implanted them on uterine defects of female Wistar rats to investigate the bio-compatibility and regenerative potential of the bio-scaffolds. Finally, we performed immunostaining to investigate the potential role of circulating stem cells in recellularization of the implanted bio-scaffolds.
The outcomes of this investigation confirmed the efficacy of the proposed protocol to provide whole human uterine scaffolds with characteristics and extra-cellular matrix components similar to the native human uterus. Subsequent in vivo studies demonstrated the bio-compatibility and the regenerative potential of the scaffolds and suggested a signaling pathway as an underlying mechanism for the regenerative process.
To the best of our knowledge, this investigation provides the first efficient perfusion-based decellularization protocol for the human uterus to obtain whole-organ scaffolds. The outcomes of this investigation could be employed in future human uterus tissue engineering studies which could ultimately result in the development of novel treatments for female infertile patients.
本研究旨在设计一种基于灌注的去细胞化方案，为完整的人子宫生物支架提供保留结构和组成特征，并研究去细胞化组织的体内特性。
通过蠕动泵经子宫动脉灌注十二烷基硫酸钠（SDS），对 8 个人体子宫进行灌注式去细胞化。对生物支架进行评估，并与天然人子宫进行比较，比较其组织学、免疫组织化学、结构和生物力学特性，此外还进行 CT 血管造影术以检查血管网络的保留情况。随后，我们获得去细胞贴片并将其植入雌性 Wistar 大鼠的子宫缺陷部位，以研究生物支架的生物相容性和再生潜力。最后，我们进行免疫染色，以研究循环干细胞在植入生物支架再细胞化中的潜在作用。
本研究的结果证实了所提出的方案能够有效地为完整的人子宫提供具有类似于天然人子宫的特征和细胞外基质成分的支架。随后的体内研究表明了支架的生物相容性和再生潜力，并提出了一种信号通路作为再生过程的潜在机制。
据我们所知，本研究首次为人类子宫提供了一种有效的基于灌注的去细胞化方案，以获得完整的器官支架。本研究的结果可应用于未来的人类子宫组织工程研究，最终可能为女性不孕患者开发出新的治疗方法。
