脐带干细胞裂解物:一种用于假定治疗急性颞下颌关节炎症的新型生物注射剂。

Umbilical Cord Stem Cell Lysate: A New Biologic Injectate for the Putative Treatment of Acute Temporomandibular Joint Inflammation.

作者信息

Ward Christopher K, Gill Rita G, Liddell Robert S, Davies John E

机构信息

Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada.

Institute of Biomedical Engineering (BME), University of Toronto, Toronto, Ontario, Canada.

出版信息

J Inflamm Res. 2023 Sep 27;16:4287-4300. doi: 10.2147/JIR.S420741. eCollection 2023.

Abstract

OBJECTIVE

To compare in vivo, the acute anti-inflammatory effects of a lysate derived from human umbilical perivascular mesenchymal cells with the cells themselves in both an established hind-paw model of carrageenan-induced inflammation and also in the inflamed temporomandibular joint.

STUDY DESIGN

Human umbilical cord perivascular cells were harvested and cultured in xeno- and serum-free conditions to P3. In addition, P3 cells were used to prepare a proprietary 0.22 micron filtered lysate. First, CD1 immunocompetent mice underwent unilateral hind-paw injections of carrageenan for induction of inflammation, followed immediately by treatment with saline (negative control), 1% cell lysate, or viable cells. The contralateral paw remained un-injected with carrageenan. Paw circumference was measured prior to injections and 48 hr later and myeloperoxidase and TNF-alpha concentrations were measured post-sacrifice in excised tissue. Second, immunocompetent Male Wistar rats underwent unilateral intra-articular temporomandibular (TMJ) injections from the same treatment groups and were sacrificed at 4 and 48 hr post-injection. The contralateral TMJ remained un-injected with carrageenan. Articular tissue and synovial aspirates, from the treated TMJ were obtained for histologic and leukocyte infiltration analyses.

RESULTS

The lysate and cell-treated hind-paw demonstrated reduced tissue edema, and significantly lower concentrations of myeloperoxidase and TNF-alpha at 48 hr compared to untreated controls. Treated TMJs demonstrated lower concentrations of leukocytes in the synovium compared to controls and histologic evidence, in the peri-articular tissue, of reduced inflammation.

CONCLUSION

In this preliminary study, both the human umbilical perivascular cells and a highly diluted lysate produced therefrom were anti-inflammatory.

摘要

目的

在体内比较人脐周间充质细胞裂解物与细胞本身在已建立的角叉菜胶诱导的后爪炎症模型以及颞下颌关节炎症模型中的急性抗炎作用。

研究设计

采集人脐带周细胞并在无血清、无异种蛋白条件下培养至P3代。此外,用P3代细胞制备一种经0.22微米过滤的专利裂解物。首先,对CD1免疫活性小鼠进行单侧后爪注射角叉菜胶以诱导炎症,随后立即用生理盐水(阴性对照)、1%细胞裂解物或活细胞进行治疗。对侧后爪不注射角叉菜胶。在注射前和48小时后测量后爪周长,并在处死动物后测量切除组织中的髓过氧化物酶和肿瘤坏死因子-α浓度。其次,对免疫活性雄性Wistar大鼠进行相同治疗组的单侧颞下颌关节内注射,并在注射后4小时和48小时处死。对侧颞下颌关节不注射角叉菜胶。获取治疗侧颞下颌关节的关节组织和滑膜抽吸物进行组织学和白细胞浸润分析。

结果

与未治疗的对照组相比,裂解物和细胞处理的后爪在48小时时组织水肿减轻,髓过氧化物酶和肿瘤坏死因子-α浓度显著降低。与对照组相比,治疗后的颞下颌关节滑膜中的白细胞浓度较低,关节周围组织有炎症减轻的组织学证据。

结论

在这项初步研究中,人脐周间充质细胞及其产生的高度稀释裂解物均具有抗炎作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cb4/10544118/7f4ddb5b0fc5/JIR-16-4287-g0003.jpg

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