Chang Mingyang, Liu Juan, Guo Baolin, Fang Xin, Wang Yi, Wang Shuyong, Liu Xiaofang, Reid Lola M, Wang Yunfang
Stem Cell and Tissue Engineering Lab, Institute of Health Service and Transfusion Medicine, Beijing, China.
Translational Research Center, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China.
Front Bioeng Biotechnol. 2020 Feb 21;8:110. doi: 10.3389/fbioe.2020.00110. eCollection 2020.
Severe skin wounds are often associated with large areas of damaged tissue, resulting in substantial loss of fluids containing electrolytes and proteins. The net result is a vulnerability clinically to skin infections. Therapies aiming to close these large openings are effective in reducing the complications of severe skin wounds. Recently, cell transplantation therapy showed the potential for rapid re-epithelialization of severe skin wounds. Here, we show the improved effects of cell transplantation therapy using a robust protocol of efficient expansion and delivery of epidermal cells for treatment of severe skin wounds. Human skin tissues were used to generate human epidermal organoids maintained under newly established culture conditions. The human epidermal organoids showed an improved capacity of passaging for at least 10 rounds, enabling organoids to expand to cell numbers required for clinical applications. A newly designed auto micro-atomization device (AMAD) was developed for delivery of human epidermal organoids onto the sites of severe skin wounds enhancing uniform and concentrated delivery of organoids, facilitating their engraftment and differentiation for skin reconstitution. With the optimal design and using pneumatic AMAD, both survival and functions of organoids were effectively protected during the spraying process. Cells in the sprayed human epidermal organoids participated in the regeneration of the epidermis at wound sites in a mouse model and accelerated wound healing significantly. The novel AMAD and out new protocol with enhanced effects with respect to both organoid expansion and efficient transplantation will be used for clincal treatments of complex, uneven, or large-area severe skin wounds.
严重皮肤创伤常伴有大面积组织损伤，导致含有电解质和蛋白质的体液大量流失。最终结果是临床上易发生皮肤感染。旨在闭合这些大创口的治疗方法对于减少严重皮肤创伤的并发症是有效的。最近，细胞移植疗法显示出促进严重皮肤创伤快速重新上皮化的潜力。在此，我们展示了使用一种强大方案进行细胞移植治疗严重皮肤创伤的改善效果，该方案能高效扩增和递送表皮细胞。使用人类皮肤组织在新建立的培养条件下生成人类表皮类器官。这些人类表皮类器官显示出至少传代10次的能力得到改善，使类器官能够扩增到临床应用所需的细胞数量。开发了一种新设计的自动微雾化装置（AMAD），用于将人类表皮类器官递送至严重皮肤创伤部位，增强类器官的均匀和集中递送，促进其植入和分化以进行皮肤重建。通过优化设计并使用气动AMAD，在喷雾过程中类器官的存活和功能均得到有效保护。喷雾后的人类表皮类器官中的细胞参与小鼠模型伤口部位表皮的再生，并显著加速伤口愈合。这种新型AMAD以及我们在类器官扩增和高效移植方面具有增强效果的新方案将用于复杂、不平整或大面积严重皮肤创伤的临床治疗。
