联合抗生素和干细胞对抗骨感染

2020/11/23 11:15:37 本站原创 佚名 【字体:

廖联明 编辑

 

植入器械引起的骨感染很难治疗,通常需要长期的抗生素治疗。在一项新的研究中,来自金泽大学的研究人员发现,由抗生素和富含抗生素的干细胞组成的联合治疗可以有效地治疗与植入器械有关的骨感染。

骨折通常需要植入器械来稳定和有效愈合骨折。然而,严重的骨髓炎只能通过长时间的抗生素来治疗。这反过来又有可能导致抗药性细菌的产生。虽然目前正在努力开发新的抗生素来抵抗这些耐药细菌,但另一种途径是研究干细胞的抗生素效应。其中一种是所谓的间充质干细胞,它自然存在于骨髓和脂肪组织中,并且已经被证明具有抗菌特性。

“脂肪源性干细胞(ADSCs)有一个明显的优势,即在皮下脂肪组织中含量丰富,因此可以很容易地获得,”该研究的通讯作者塔蒙·卡巴塔说我们的研究目的是研究ADSCs与抗生素环丙沙星联合应用对种植体相关骨感染动物模型的治疗效果。

为了实现他们的目标,研究人员首先关注环丙沙星对ADSCs的影响,并发现在最初的24小时内,随着ADSCs在抗生素培养液中的时间的延长,,细胞有效吸附的抗生素增加,而环丙沙星对干细胞的功能或活性没有不良影响。研究人员随后在体外(在试管中)测试了这些携带抗生素的ADSCs的抗菌活性,发现它们能有效地降低金黄色葡萄球菌(S.aureus)的生长,而金黄色葡萄球菌也是引起骨移植后导致感染的主要微生物。

但这种新的方法是否也能减轻活体组织中与植入物相关的感染?研究人员在老鼠身上测试了这一点,他们用涂有金黄色葡萄球菌的螺丝钉植入骨。大鼠术后7天出现骨髓炎。然后,研究人员给这些动物注射以下药物之一:载环丙沙星的ADSCs,单独的ADSCs,单独的环丙沙星,或者根本不治疗。由于骨髓炎会导致感染部位的软组织肿胀和脓肿形成,研究人员对动物的疾病程度进行了量化,发现只有载环丙沙星的ADSCs才是有效的治疗方法。研究人员利用小型计算机断层成像技术对受影响的骨骼进行可视化,进一步发现载ADSC的环丙沙星可减少骨溶解或骨降解的发生,这不仅对骨骼健康很重要,而且对移植物的稳定性也很重要。

“这些惊人的结果表明,ADSCs可以有效地装载抗生素来发挥强大的抗菌作用。卡巴塔说:“我们的研究结果为植入物相关骨髓炎提供了一种潜在的新疗法,传统的仅用抗生素治疗是不够的。”。

 

英文原文:

Coupling antibiotics with stem cells to fight off bone infections

 

Bone infections caused by implants are difficult to treat and usually require a prolonged course of antibiotic treatment. In a new study, researchers from Kanazawa University discovered that implant-related bone infections can be effectively treated with a combinational treatment consisting of antibiotics and antibiotic-laden stem cells.

 

Bone fractures often require implants for stabilization and effective healing of the broken bone. However, implants can cause serious bone infections, such as osteomyelitis, that can only be managed with a prolonged antibiotic treatment. This in turn bears the risk of contributing to the development of antibiotic-resistant bacteria. While major efforts are currently underway to develop new antibiotics that cover these antibiotic-resistant bacteria, a different path has been to study the antibiotic effects of stem cells. One type is the so-called mesenchymal stem cells that naturally reside in the bone marrow and adipose tissue, among others, and that have been shown to possess antimicrobial properties.

 

"Adipose-derived stem cells, or ADSCs, have the distinct advantage of being abundant in subcutaneous adipose tissues and can thus be easily harvested," says the corresponding author of the study Tamon Kabata. "The goal of our study was to investigate the therapeutic effects of ADSCs in combination with the antibiotic ciprofloxacin in an animal model of implant-related bone infection."

 

To achieve their goal, the researchers first focused on the effects of ciprofloxacin on ADSCs and found an efficient, time-dependent loading of ADSCs with the antibiotic in the first 24 hours with no adverse effects of ciprofloxacin on the function or viability of the stem cells. The researchers then tested the antimicrobial activity of the antibiotic-loaded ADSCs in vitro (in a tube) and found that they effectively decreased the growth of the bacterium S. aureus, which is also the main microbe causing bone implant-related infections.

 

But could this novel approach also mitigate implant-related infection in a living organism? The researchers tested this on rats, who received bone implants using screws coated with S. aureus bacteria. The rats developed osteomyelitis 7 days after surgery. Then, the researchers administered one of the following to the animals: ADSCs loaded with ciprofloxacin, ADSCs alone, ciprofloxacin alone, or no treatment at all. Because osteomyelitis can lead to soft tissue swelling and abscess formation at the site of the infection, the researchers quantified the extent of the disease in the animals and found that only ADSCs loaded with ciprofloxacin presented as an effective treatment. Using the imaging modality micro-computed tomography to visualize the affected bones, the researchers further found that ADSC-loaded ciprofloxacin decreased the appearance of osteolysis, or bone degradation, which is not only important for bone health, but also for the stability of the implant.

 

"These are striking results that show how ADSCs can efficiently be loaded with antibiotics to exert a strong antimicrobial effect. Our findings suggest a potential novel therapy for implant-associated osteomyelitis, for which conventional treatment with only antibiotics is usually insufficient," says Kabata.

 

Journal Reference:

期刊参考:

Junya Yoshitani, Tamon Kabata, Hiroshi Arakawa, Yukio Kato, Takayuki Nojima, Katsuhiro Hayashi, Masaharu Tokoro, Naotoshi Sugimoto, Yoshitomo Kajino, Daisuke Inoue, Ken Ueoka, Yuki Yamamuro, Hiroyuki Tsuchiya. Combinational therapy with antibiotics and antibiotic-loaded adipose-derived stem cells reduce abscess formation in implant-related infection in rats. Scientific Reports, 2020; 10 (1) DOI: 10.1038/s41598-020-68184-y

相关阅读: