Intravenous administration of allogeneic Wharton jelly-derived mesenchymal stem cells for treatment of dogs with congestive heart failure secondary to myxomatous mitral valve disease.
Intravenous administration of allogeneic Wharton jelly-derived mesenchymal stem cells for treatment of dogs with congestive heart failure secondary to myxomatous mitral valve disease.
复制标题
静脉注射同种异体沃顿凝胶来源的间充质干细胞治疗二尖瓣粘液瘤性疾病继发充血性心力衰竭。
DOI：
10.2460/ajvr.82.6.487
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发表时间：
2021-06
影响因子：
1
通讯作者：
Hoffman AM
中科院分区：
文献类型：
--
作者：
Yang VK;Meola DM;Davis A;Barton B;Hoffman AM
评价间充质干细胞（MSC）是否可以安全地静脉注射到继发于粘液瘤性二尖瓣疾病（MMVD）的充血性心力衰竭（CHF）犬中，以改善心功能并延长生存时间。10只客户拥有的犬继发于MMVD的CHF。在一项双盲、安慰剂对照临床试验中入组了继发于MMVD的CHF首次发作犬。MSC组中的5只狗接受同种异体沃顿商学院来源的MSC（2 × 106个细胞/kg，IV），安慰剂组中的5只狗接受1%自体血清溶液（IV），间隔3周注射3次。细胞释放标准包括三系分化、表达CD 44和CD 90而不表达CD 34和主要组织相容性复合物II类、正常核型和不存在病原微生物污染。患者随访6个月或直至死亡或安乐死。在首次注射前和注射后4小时以及末次注射后每3个月获得超声心动图数据、ECG结果、血清心脏生物标志物浓度、CBC和血清生化分析结果。淋巴细胞和嗜酸性粒细胞计数在注射后4小时显著降低，单核细胞仅在接受MSC注射的犬中显著降低。两组之间的超声心动图变量、ECG结果、血清心脏生物标志物浓度、生存时间和至首次利尿药物剂量递增的时间无显著差异。这项研究表明，可以很容易地从犬沃顿胶质中收集MSC作为同种异体MSC来源，并可以安全地IV输送给继发于MMVD的CHF犬。
To evaluate whether mesenchymal stem cells (MSCs) can be safely administered IV to dogs with congestive heart failure (CHF) secondary to myxomatous mitral valve disease (MMVD) to improve cardiac function and prolong survival time. 10 client-owned dogs with CHF secondary to MMVD. Dogs with an initial episode of CHF secondary to MMVD were enrolled in a double-blind, placebo-controlled clinical trial. Five dogs in the MSC group received allogeneic Wharton jelly–derived MSCs (2 × 106 cells/kg, IV), and 5 dogs in the placebo group received a 1% solution of autologous serum (IV) for 3 injections 3 weeks apart. Cell-release criteria included trilineage differentiation, expression of CD44 and CD90 and not CD34 and major histocompatability complex class II, normal karyotype, and absence of contamination by pathogenic microorganisms. Patients were followed for 6 months or until death or euthanasia. Echocardiographic data, ECG findings, serum cardiac biomarker concentrations, CBC, and serum biochemical analysis results were obtained prior to and 4 hours after the first injection and every 3 months after the final injection. Lymphocyte and eosinophil counts decreased significantly 4 hours after injection, and monocytes decreased significantly only in dogs that received an MSC injection. No significant differences were seen in the echocardiographic variables, ECG results, serum cardiac biomarker concentrations, survival time, and time to first diuretic drug dosage escalation between the 2 groups. This study showed that MSCs can be easily collected from canine Wharton jelly as an allogeneic source of MSCs and can be safely delivered IV to dogs with CHF secondary to MMVD.