犬头面部复合组织同种异体移植模型的建立

目的建立犬头面部复合组织同种异体移植的实验动物模型。方法①解剖研究：用4只杂种犬进行头面颈部的解剖及复合组织瓣的切取研究。②自体回植（Ⅰ组n=5）：为选择最佳的复合组织瓣移植方式，进行了三种形式的复合组织瓣白体回植。③异体移植（Ⅱ组n=6）：以第三种复合组织瓣及其改良的组织瓣形式进行了两种头面部复合组织异体移植。免疫抑制治疗方案为环孢霉素A和皮质激素联合应用，依据环孢霉素A血药浓度调整用药剂量。分别在术后4、6、12周及6个月对眼轮匝肌进行肌电图检测。结果①犬头面部的解剖特征与人相似，以颈外动静脉为血管蒂能够为头面部复合组织瓣提供良好的血供。②IC组两只犬长期存活，但出现唾液漏。③Ⅱa组中1只犬于移植术后28d免疫排斥，通过调整环孢霉素A及强的松的用量并局部应用氯倍他索涂抹，2周后治愈，现已存活309d。Ⅱb组中3只犬现已分别存活159、129和108d，无并发症，肌电图显示眼轮匝肌功能逐步恢复。结论改良犬单侧上半头面部组织瓣异体移植模型是研究头面部复合组织异体移植的理想模型。     

异体面部移植的现状分析

各种严重外伤、肿瘤以及先天畸形常常可导致患者面容毁损,而异体面部移植可以在一次手术中矫正所有严重畸形,并且能达到兼顾功能和美观的效果。截至2018年,全世界实施的部分或全面部移植手术达到44例,此项手术属于非挽救生命的手术,存在很多问题和争议。作者结合以往经验,对手术适应证选择、手术原则和细节、术后并发症的防治、免疫抑制方案、术后功能恢复、伦理学问题、社会经济学问题等方面进行分析讨论。     

同种异体复合组织移植的免疫治疗进展

同种异体复合组织移植是现今修复再造领域的一种新选择,但术后的免疫排斥是公认的医学难题.近年来由于复合组织移植数量的增多,使术后的免疫抑制方案成为新热点,本文介绍并总结了同种异体复合组织移植后免疫抑制治疗的进展及应用.     

复合组织同种异体移植的治疗进展

复合组织同种异体移植（composite tissue allotransplantation，CTA）给重建外科的发展带来了很大的期望，目前手、喉膝关节等器官或复合组织同种异体移植已经在临床实践中取得了很大的进步，在先天性和后天获得性周围组织缺损临床应用中显示很大的潜能。     

同种异体面部复合组织移植修复严重面部烧伤的脸外型和功能

同种异体面部复合组织移植（facial tissue allotransplantation,FTA）治疗严重面部毁损的疗效已证实。与传统修复重建方法比较,FTA一次手术即可修复严重外伤或肿瘤切除术后造成的面部复合组织缺损,而且在面部基本功能恢复和美观方面效果更佳。     

同种异体全手与手指复合组织移植的发展趋势

手丧失后,人的劳动能力与生活质量受到严重影响,患者迫切希望手再生,医学专家亦积极进行了同种异体肢体移植的实验研究。20世纪50年代以来,Goldwyn(1956),Schwind(1962),Lance(1971),Lapchinsky(1973),陈中伟(1981)等先后在动物身上进行异体肢体移植,均因排斥反应而失败。Benhaim(1993),Murasmatsu(1997)用新一代的强力免疫抑制药物如RS-61443、FK506等已经取得异体肢体在动物宿主身上较久存活的成绩。     

同种异体组织冷冻保存和移植的研究

冷冻保存可以长时间保存组织的活性和功能,并且调整同种异体组织的抗原表达,但也会造成组织和细胞的损伤。临床研究用冷冻技术能有效保存体外培养的细胞,但在冷冻保存用于同种异体移植的复合组织方面还存在问题,需要进一步研究,才能应用于临床。     

同种异体复合组织移植的免疫研究进展

目的了解同种异体复合组织移植的免疫研究进展。方法查阅相关文献,对同种异体复合组织移植的免疫特点、实验进展、临床经验等进行总结。结果同种异体复合组织位于体表,包含组织成分复杂,抗原性高。其移植后在免疫抑制剂用药方案、排斥反应的诊断以及慢性排斥反应发生率等许多方面同内脏器官移植有不同的特点。结论在下一步研究中,应吸取同种异体复合组织移植独特的经验教训,在诱导耐受、局部用药、排斥诊断等方面树立同种异体复合组织的独特标准。     

同种异体全颜面复合组织移植进展

先天或后天原因(如烧伤、创伤及广泛的肿瘤切除)所致颜面部严重的缺损与畸形，目前一般采用游离植皮、皮瓣转移、皮肤扩张术等方法进行修复，虽然可以明显改善外形，部分或全部恢复功能，但与正常颜面比较，存在颜色、质地、轮廓和面部表情活动等多方面的差异，修复后的外形常与正常容貌相差太远，且常需多次手术。而且颜面不只是表面的一层皮肤，深部有皮下脂肪和表情肌，     

复合组织异体移植后功能恢复的研究进展

复合组织异体移植（composite tissue allotra nsplantation，CTA），如手、颜面、喉、腹壁移植等，相对于组织结构相对单一的肾、肝、心、肺等实质性内脏器官移植而言，是指两种或两种以上组织结构的异体移植，包括皮肤、皮下组织、骨、肌肉、神经、血管等组织的部分或全部。实体器官移植常常是为了挽救患者生命，而复合组织移植的目的在于修复患者某个功能部位的缺失，     

Mixed allogeneic chimerism and tolerance to composite tissue allografts

The development of effective immunosuppressive drugs has made solid organ allotransplantation the preferred approach for treatment of end-organ failure. The benefits of these immunosuppressants outweigh their risks in preventing rejection of lifesaving solid-organ allografts. On the contrary, composite tissue allotransplants are non-lifesaving and whether the risks of immunosuppressants justify their benefits is a subject of debate. Hence, composite tissue allografts (CTA) have not enjoyed widespread clinical application for reconstruction of large tissue defects. Therefore, a method of preventing rejection that would eliminate the need for toxic immunosuppressants is of particular importance in CTA. Bone marrow transplantation (BMT) to establish mixed chimerism induces tolerance to a variety of allografts in animal models. This article reviews mixed chimerism-based tolerance protocols. Their limitations and their relevance to CTA are discussed, highlighting some unique characteristics (high antigenicity and the presence of active bone marrow) that make CTAs different from solid organ allografts.     

Strategies for tolerance induction to composite tissue allografts

The emerging field of composite tissue transplantation offers the potential to replace lost tissues from cadaveric sources. Two major obstacles currently limit the future of composite tissue allotransplantation. The first is chronic rejection, attributed to both antibody deposition and cell-mediated destruction of transplanted tissue. The second obstacle is complications associated with the chronic use of immunosuppressive agents. Our laboratory has been investigating several strategies to induce tolerance to limb tissue allografts to provide solutions to many of the current limitations in allotransplantation. Three strategies show promise in the ability to induce tolerance to organ allografts. The first involves genetic matching at the HLA loci followed by a short course of immunosuppression. The second is the application of a "mixed chimerism" regimen followed by transplantation. The third is costimulatory blockade using a short course of monoclonal antibodies, such as anti-CD40 ligand and CTLA4-Ig after transplantation. Inducing a state of tolerance to limb allografts would eliminate the need for chronic immunosuppression and may also prevent the onset of chronic rejection. The ability to induce allograft tolerance would greatly expand the indications for composite tissue transplantation.     

Tissue engineering: bridging the gap between replantation and composite tissue allografts

This article explores issues related to tissue engineering and composite tissue allografts that employ physiologic and anatomic autogenous replicates to restore tissue loss. Composite tissue allotransplantation has become a controversial option for reconstruction, most prominently for reconstruction involving the hand and, recently, the face. While the side-effect profile of systemic immunosuppression continues to improve, the long-term risks of immunosuppression leaves composite tissue allotransplantation a domain for cautious exploration. Meanwhile, tissue engineering could, conceivably, be the gap between replantation and composite tissue allografts. Whereas the perils of immunosuppression may limit the routine use of allografts, employing constructions made of the patient's own cells negates the need for any antirejection therapy.     

Impact of donor bone marrow on survival of composite tissue allografts

Composite tissue allotransplants (CTA) involves transplantation of various tissues including vessels, nerves, skin, and immune cells and bears significant antigenic load. Different immunosuppressive protocols are used for experimental and clinical CTA. Immunosuppressive agents maintain survival of the different components of composite tissue allografts. However, the potential side effects of chronic immunosuppression currently limit the widespread application of CTA transplants. Bone marrow therapy in many tolerance induction protocols therefore provides a guide to reaching the target of permanent immunotolerance. Multiple studies suggest that bone marrow is immunomodulatory and may facilitate allograft acceptance.In this review, bone marrow-based therapy protocols of experimental and clinical models are presented in composite tissue transplantation.     

A heterotopic primate model for facial composite tissue transplantation

The purpose of this study was to develop a nonhuman primate model for heterotopic composite tissue facial transplantation in which to study the natural history of facial transplantation and evaluate immunosuppressive regimens.A composite oromandibular facial segment transplant based on the common carotid artery was evaluated. Flaps from 7 cynomolgus monkeys were transplanted to the groins of 7 recipients at the superficial femoral artery and vein. The immunosuppressive regimen consisted of thymoglobulin, rapamycin, and tacrolimus. Allograft survival ranged from 6 to 129 days. Histology performed in the long-term survivor at the time of necropsy revealed extensive inflammation and necrosis of the allograft skin; however, muscle and bone elements were viable, with minimal inflammation.This heterotopic facial transplantation model avoids the potential morbidity of mandibular resection and orthotopic facial transplantation. Our work also concurs with the work of other groups who found that the skin component is the most antigenic.