Pereira Joyce Carvalho, Ramos Tadeu Diniz, Silva Johnatas Dutra, de Mello Mirian França, Pratti Juliana Elena Silveira, da Fonseca-Martins Alessandra Marcia, Firmino-Cruz Luan, Kitoko Jamil Zola, Chaves Suzana Passos, Gomes Daniel Claudio De Oliveira, Diaz Bruno Lourenço, Rocco Patricia R M, de Matos Guedes Herbert Leonel
Laboratório de Inflamação, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Laboratório de Investigação Pulmonar, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Front Immunol. 2017 Aug 10;8:893. doi: 10.3389/fimmu.2017.00893. eCollection 2017.
Cutaneous leishmaniasis remains both a public health and a therapeutic challenge. To date, no ideal therapy for cutaneous leishmaniasis has been identified, and no universally accepted therapeutic regimen and approved vaccines are available. Due to the mesenchymal stromal cell (MSC) immunomodulatory capacity, they have been applied in a wide variety of disorders, including infectious, inflammatory, and allergic diseases. We evaluated the potential effects of bone marrow MSC therapy in a murine model of cutaneous leishmaniasis. , coculture of infected macrophages with MSC increased parasite load on macrophages in comparison with controls (macrophages without MSCs). , BALB/c mice were infected with 2 × 10 (Josefa strain) promastigotes in the footpad. 7 and 37 days after infection, animals were treated with 1 × 10 MSCs, either intralesional (i.l.), i.e., in the same site of infection, or intravenously (i.v.), through the external jugular vein. Control animals received the same volume (50 µL) of phosphate-buffered saline by i.l. or i.v. routes. The lesion progression was assessed by its thickness measured by pachymetry. Forty-two days after infection, animals were euthanized and parasite burden in the footpad and in the draining lymph nodes was quantified by the limiting dilution assay (LDA), and spleen cells were phenotyped by flow cytometry. No significant difference was observed in lesion progression, regardless of the MSC route of administration. However, animals treated with i.v. MSCs presented a significant increase in parasite load in comparison with controls. On the other hand, no harmful effect due to MSCs i.l. administered was observed. The spleen cellular profile analysis showed an increase of IL-10 producing T CD4 and TCD8 cells in the spleen only in mice treated with i.v. MSC. The excessive production of IL-10 could be associated with the disease-aggravating effects of MSC therapy when intravenously administered. As a conclusion, in the current murine model of -induced cutaneous disease, MSCs did not control the damage of cutaneous disease and, depending on the administration route, it could result in deleterious effects.
皮肤利什曼病仍然是一个公共卫生和治疗方面的挑战。迄今为止，尚未确定治疗皮肤利什曼病的理想疗法，也没有普遍接受的治疗方案和获批的疫苗。由于间充质基质细胞（MSC）具有免疫调节能力，它们已被应用于多种疾病，包括感染性、炎症性和过敏性疾病。我们在皮肤利什曼病的小鼠模型中评估了骨髓间充质干细胞治疗的潜在效果。与对照组（不含间充质干细胞的巨噬细胞）相比，感染的巨噬细胞与间充质干细胞共培养会增加巨噬细胞上的寄生虫载量。将2×10（约瑟法菌株）前鞭毛体接种于BALB/c小鼠的足垫。感染后7天和37天，动物通过病灶内注射（即注射到感染的同一部位）或静脉注射（通过颈外静脉）接受1×10个间充质干细胞治疗。对照动物通过病灶内或静脉途径接受相同体积（50µL）的磷酸盐缓冲盐水。通过测厚法测量病变厚度来评估病变进展。感染后42天，对动物实施安乐死，并通过极限稀释法（LDA）对足垫和引流淋巴结中的寄生虫负荷进行定量，通过流式细胞术对脾细胞进行表型分析。无论间充质干细胞的给药途径如何，在病变进展方面均未观察到显著差异。然而，与对照组相比，接受静脉注射间充质干细胞治疗的动物的寄生虫载量显著增加。另一方面，未观察到病灶内注射间充质干细胞产生的有害影响。脾细胞分析表明，仅在接受静脉注射间充质干细胞治疗小鼠的脾脏中，产生白细胞介素-10的CD4+T细胞和CD8+T细胞有所增加。静脉注射时，白细胞介素-10的过度产生可能与间充质干细胞治疗的疾病加重作用有关。总之，在当前的小鼠皮肤疾病模型中，间充质干细胞无法控制皮肤疾病的损害，并且根据给药途径的不同，可能会产生有害影响。
