Division of Transplant Medicine, Mayo Clinic, Jacksonville, Florida, USA.
Division of Biomedical Statistics and Informatics, Mayo Clinic, Jacksonville, Florida, USA.
Stem Cells Transl Med. 2018 Feb;7(2):161-167. doi: 10.1002/sctm.17-0198. Epub 2018 Jan 11.
Feasibility, tolerance, and safety of intravenous infusions of allogeneic mesenchymal stem cell (MSC) therapy in lung transplant recipients with bronchiolitis obliterans syndrome (BOS) are not well established. MSCs were manufactured, cryopreserved, transported to our facility, thawed, and infused into nine recipients with moderate BOS (average drop in forced expiratory volume in 1 second was 56.8% ± 3.2% from post-transplant peak) who were refractory to standard therapy and not candidates for retransplant. Cells were viable and sterile prior to infusion. Patients received a single infusion of either 1 (n = 3), 2 (n = 3), or 4 (n = 3) million MSCs per kg. Patients were medically evaluated before; during; and at 24 hours, 1 week, and 1 month after infusion for evidence of infusion-related adverse events and tolerance of therapy. Vital signs, pulmonary function test results, Borg Dyspnea Index, and routine laboratory data were recorded. Vital signs and O saturation did not significantly change during or up to 2 hours after MSC infusion. There were no significant changes in gas exchange variables, pulmonary function test results, or laboratory values at 1, 7, and 30 days postinfusion compared with preinfusion values. Infusion of MSCs in patients with BOS was feasible, safe, and well tolerated and did not produce any significant adverse changes in clinical, functional, or laboratory variables during or up to 30 days after infusion. Manufacturing, transport, and administration of intravenous, allogeneic bone marrow-derived MSCs in doses from 1 to 4 million MSCs per kg is safe in lung transplant recipients with BOS. Stem Cells Translational Medicine 2018;7:161-167.
静脉输注同种异体间充质干细胞（MSC）治疗肺移植后闭塞性细支气管炎综合征（BOS）患者的可行性、耐受性和安全性尚未得到充分证实。我们将 MSCs 制成、冷冻保存、运送到我们的设施，解冻后输注给 9 名中度 BOS 患者（从移植后峰值开始，用力呼气量的平均下降率为 56.8%±3.2%），这些患者对标准治疗无反应且不适合再次移植。在输注前，细胞具有活力且无菌。患者接受单次输注 1（n=3）、2（n=3）或 4（n=3）百万个/kg 的 MSCs。患者在输注前、输注期间和输注后 24 小时、1 周和 1 个月接受医学评估，以评估与输注相关的不良反应和治疗耐受性。记录生命体征、肺功能测试结果、Borg 呼吸困难指数和常规实验室数据。在 MSC 输注期间和输注后 2 小时内，生命体征和 O 饱和度没有显著变化。与输注前相比，在输注后 1、7 和 30 天，气体交换变量、肺功能测试结果或实验室值没有显著变化。在 BOS 患者中输注 MSCs 是可行的、安全的且耐受性良好，在输注期间或输注后 30 天内，不会在临床、功能或实验室变量上产生任何显著的不良反应变化。在 BOS 的肺移植受者中，以 1 至 400 万个/kg 的剂量制造、运输和管理静脉内同种异体骨髓源性 MSC 是安全的。《干细胞转化医学》2018；7：161-167。
