Division of Pediatric Surgery and Developmental Biology and Regenerative Medicine, Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, California.
Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California.
Tissue Eng Part A. 2020 Apr;26(7-8):411-418. doi: 10.1089/ten.TEA.2019.0178. Epub 2019 Dec 12.
Splenectomy is common after trauma or hematologic disease, and alters immune protection against pathogens, which may lead to fulminant infection with high mortality. Yet the spleen has demonstrable regenerative capacity and cells might be recovered and reimplanted at the time of injury or excision to avoid these risks. Tissue-engineered spleen (TESp) was generated from mice (mTESp) or human donor spleen (hTESp) through implantation of spleen organoid units (spleen OU), in NOD/SCID mice with concurrent splenectomy, on a biodegradable scaffold. Explants were evaluated and blood smears were obtained to investigate the presence of target cells or Howell-Jolly bodies, which are erythrocyte sequelae of asplenia. TESp was generated from mouse (mTESp) and human (hTESp) donor cells with essential splenic components: red and white pulp with trabeculae. mTESp and hTESp demonstrated green fluorescent protein- or lamin-positive costaining with proliferating cell nuclear antigen, CD4, and CD11c, identifying proliferative donor cells and key immune components of the spleen of donor origin. Animals with hTESp and mTESP combined with splenectomy had significantly fewer Howell-Jolly bodies on blood smears than controls. TESp from mouse and human donor cells can be generated by 4 weeks and contains donor immune cells identified by CD4 and CD11c. TESp reduces postsplenectomy erythrocyte inclusions, indicating possible function. Impact Statement Overwhelming postsplenectomy infection is rare but highly mortal. Tissue-engineered spleen (TESp) was generated from murine (mTESp) and human (hTESp) donors and appeared histologically similar to native spleen. Both mTESp and hTESp demonstrated proliferative cells of donor spleen origin. Importantly, functional cells were demonstrated on imaging with a corresponding reduction in the number of erythrocyte inclusions in blood smears that are typically identified in patients with asplenia and indicate a lack of clearance by functional spleen tissue. Taken together, these findings indicate that this approach might be clinically relevant as a future human therapy.
脾切除术常见于创伤或血液疾病后，改变了对病原体的免疫保护，可能导致暴发性感染和高死亡率。然而，脾脏具有明显的再生能力，在受伤或切除时可以回收和再植入细胞，以避免这些风险。组织工程脾脏（TESp）是通过在 NOD/SCID 小鼠中植入脾类器官单位（spleen OU），同时进行脾切除术，在可生物降解支架上由小鼠（mTESp）或人类供体脾脏（hTESp）产生的。对植入物进行评估，并获取血涂片以研究是否存在靶细胞或 Howell-Jolly 小体，后者是脾切除术后红细胞的后遗症。mTESp 和 hTESp 均由具有基本脾脏成分的小鼠（mTESp）和人类（hTESp）供体细胞产生：红髓和白髓，带有小梁。mTESp 和 hTESp 均与增殖细胞核抗原、CD4 和 CD11c 呈绿色荧光蛋白或层粘连蛋白阳性共染色，鉴定出增殖的供体细胞和供体来源脾脏的关键免疫成分。与对照相比，接受 hTESp 和 mTESp 联合脾切除术的动物血涂片上的 Howell-Jolly 小体明显减少。4 周内可从鼠和人供体细胞生成 TESp，并用 CD4 和 CD11c 鉴定出供体免疫细胞。TESp 减少脾切除术后红细胞内含物，表明其可能具有功能。影响声明 脾切除术后感染虽罕见但死亡率极高。组织工程脾脏（TESp）是由鼠（mTESp）和人（hTESp）供体产生的，在组织学上与天然脾脏相似。mTESp 和 hTESp 均显示出供体脾脏来源的增殖细胞。重要的是，在成像上显示出功能性细胞，同时血涂片上红细胞内含物的数量减少，这些红细胞内含物通常在无脾患者中发现，表明缺乏功能性脾组织的清除。总之，这些发现表明，这种方法可能具有临床相关性，作为未来的人类治疗方法。
