Activated Mesenchymal Stromal Cell Therapy for Treatment of Multi-Drug Resistant Bacterial Infections in Dogs.
Activated Mesenchymal Stromal Cell Therapy for Treatment of Multi-Drug Resistant Bacterial Infections in Dogs.
复制标题
DOI：
10.3389/fvets.2022.925701
复制
发表时间：
2022
影响因子：
3.2
通讯作者：
中科院分区：
文献类型：
--
作者：
需要新的和创造性的方法来治疗由日益耐药的细菌菌株引起的慢性感染。一种策略是采用间充质基质细胞（MSC）直接杀死细菌并激活有效的宿主对感染的免疫力的细胞疗法。我们先前证明，全身递送的活化MSC可以与抗生素治疗一起有效地用于清除啮齿动物模型中的慢性生物膜感染。因此，我们在目前的研究中寻求对激活的犬MSC的抗菌特性的新见解，并评估其作为治疗犬中自然发生的耐药感染的新型细胞疗法的有效性。这些研究表明，犬MSC产生并分泌抗菌肽，这些抗菌肽与大多数常见抗生素协同作用，以引发快速杀菌活性。此外，激活的犬MSC更有效地迁移到炎症刺激，并分泌与伤口愈合和成纤维细胞增殖和激活的中性粒细胞的募集相关的因子。与来自活化MSC的条件培养基孵育的巨噬细胞产生显著增强的杀菌活性。通过反复静脉内递送活化的同种异体MSC治疗慢性多药耐药感染的犬的临床研究证明了显著的临床益处，包括感染清除和感染组织的愈合。总之，这些研究的结果为犬MSC的抗微生物活性及其在慢性耐药感染管理中的潜在临床应用提供了新的见解。
New and creative approaches are required to treat chronic infections caused by increasingly drug-resistant strains of bacteria. One strategy is the use of cellular therapy employing mesenchymal stromal cells (MSC) to kill bacteria directly and to also activate effective host immunity to infection. We demonstrated previously that activated MSC delivered systemically could be used effectively together with antibiotic therapy to clear chronic biofilm infections in rodent models. Therefore, we sought in the current studies to gain new insights into the antimicrobial properties of activated canine MSC and to evaluate their effectiveness as a novel cellular therapy for treatment of naturally-occurring drug resistant infections in dogs. These studies revealed that canine MSC produce and secrete antimicrobial peptides that synergize with most classes of common antibiotics to trigger rapid bactericidal activity. In addition, activated canine MSC migrated more efficiently to inflammatory stimuli, and secreted factors associated with wound healing and fibroblast proliferation and recruitment of activated neutrophils. Macrophages incubated with conditioned medium from activated MSC developed significantly enhanced bactericidal activity. Clinical studies in dogs with chronic multidrug resistant infections treated by repeated i.v. delivery of activated, allogeneic MSC demonstrated significant clinical benefit, including infection clearance and healing of infected tissues. Taken together, the results of these studies provide new insights into antimicrobial activity of canine MSC, and their potential clinical utility for management of chronic, drug-resistant infections.
登录
查看更多内容
影响因子：
2.6
作者：
Kim, Jaehyup;Hematti, Peiman
通讯作者：
Hematti, Peiman
DOI：
10.1073/pnas.0510847103
发表时间：
2006-02-07
影响因子：
11.1
作者：
Berger, T;Togawa, A;Mak, TW
通讯作者：
Mak, TW
影响因子：
5.2
作者：
Chiossone, Laura;Conte, Romana;Bottino, Cristina
通讯作者：
Bottino, Cristina
影响因子：
7.5
作者：
Harman RM;Yang S;He MK;Van de Walle GR
通讯作者：
Van de Walle GR
影响因子：
1.2
作者：
Chow L;Johnson V;Regan D;Wheat W;Webb S;Koch P;Dow S
通讯作者：
Dow S