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静脉注射同种异体牙髓间充质干细胞治疗黏液瘤性二尖瓣病继发充血性心力衰竭的犬。

Intravenous administration of allogeneic Wharton jelly-derived mesenchymal stem cells for treatment of dogs with congestive heart failure secondary to myxomatous mitral valve disease.

出版信息

Am J Vet Res. 2021 Jun;82(6):487-493. doi: 10.2460/ajvr.82.6.487.

Abstract

OBJECTIVE

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.

ANIMALS

10 client-owned dogs with CHF secondary to MMVD.

PROCEDURES

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 × 10 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.

RESULTS

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.

CONCLUSIONS AND CLINICAL RELEVANCE

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.

摘要

目的

评估骨髓间充质干细胞(MSCs)是否可安全地静脉内给予患有马方综合征相关二尖瓣关闭不全性充血性心力衰竭(CHF)的犬,以改善心功能并延长存活时间。

动物

10 只患有马方综合征相关二尖瓣关闭不全性 CHF 的患犬。

操作程序

患有马方综合征相关 CHF 初始发作的犬被纳入一项双盲、安慰剂对照临床试验。MSC 组的 5 只犬接受了同种异体 Wharton 胶衍生的 MSCs(2×10 个细胞/kg,静脉内),而安慰剂组的 5 只犬接受了 1%的自体血清溶液(静脉内),3 周内注射 3 次。细胞释放标准包括三系分化、CD44 和 CD90 的表达以及 CD34 和主要组织相容性复合体 II 类的缺失、正常核型和无致病微生物污染。对患者进行了 6 个月或直至死亡或安乐死的随访。在第 1 次注射前和第 1 次注射后 4 小时以及最后 1 次注射后每 3 个月,均获得了超声心动图数据、心电图结果、血清心脏生物标志物浓度、全血细胞计数和血清生化分析结果。

结果

注射后 4 小时,淋巴细胞和嗜酸性粒细胞计数显著下降,仅接受 MSC 注射的犬的单核细胞计数显著下降。2 组间超声心动图变量、心电图结果、血清心脏生物标志物浓度、存活时间和首次利尿剂药物剂量升级时间均无显著差异。

结论和临床相关性

本研究表明,MSCs 可从犬 Wharton 胶中轻松获得,作为 MSC 的同种异体来源,可安全地静脉内给予患有马方综合征相关二尖瓣关闭不全性 CHF 的犬。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e34/8224903/6933db78a8fe/nihms-1712752-f0001.jpg

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