Single-Cell RNA-Sequencing Identifies Infrapatellar Fat Pad Macrophage Polarization in Acute Synovitis/Fat Pad Fibrosis and Cell Therapy.
Single-Cell RNA-Sequencing Identifies Infrapatellar Fat Pad Macrophage Polarization in Acute Synovitis/Fat Pad Fibrosis and Cell Therapy.
复制标题
DOI：
10.3390/bioengineering8110166
复制
发表时间：
2021-10-29
期刊：
影响因子：
--
通讯作者：
Griswold AJ
中科院分区：
文献类型：
--
作者：
Kouroupis D;Best TM;Kaplan LD;Correa D;Griswold AJ
膝关节炎症病理的发病和进展部分是由髌下脂肪垫（IFP）中的巨噬细胞调节的，因此，巨噬细胞向促炎（M1）或抗炎（M2）表型的极化在关节疾病病理中很重要。M1/M2平衡的改变有助于关节炎症的发生和进展，并可能通过间充质干细胞（MSC）治疗而改变。在急性滑膜/IFP炎症大鼠模型中，进行单次关节内注射IFP- msc，对照组为(1)未接受IFP- msc的患病大鼠和(2)未患病大鼠。4天后，通过单细胞rna测序对各组分离的IFP组织进行细胞特异性转录谱分析。在所有三个治疗组中，IFP内鉴定出八个转录组不同的细胞群，各组间骨髓细胞的比例有显著差异。巨噬细胞以髓系细胞为主（>占90%）；一个M1亚簇高表达促炎标志物，两个M2亚簇，其中一个表达较高水平的标准M2标志物。值得注意的是，与健康样本（14.8%）和MSC处理样本（19.4%）相比，患病样本（11.9%）表达M2标记物的细胞比例最低。这些结果表明，在急性炎症模型中，IFP巨噬细胞向促炎M1表型分化，这可以通过IFP- msc治疗诱导M2状态转换来缓解。了解IFP细胞异质性和相关的转录程序可能为致残关节疾病病理的新治疗策略提供见解。
The pathogenesis and progression of knee inflammatory pathologies is modulated partly by residing macrophages in the infrapatellar fat pad (IFP), thus, macrophage polarization towards pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes is important in joint disease pathologies. Alteration of M1/M2 balance contributes to the initiation and progression of joint inflammation and can be potentially altered with mesenchymal stem cell (MSC) therapy. In an acute synovial/IFP inflammation rat model a single intra-articular injection of IFP-MSC was performed, having as controls (1) diseased rats not receiving IFP-MSC and (2) non-diseased rats. After 4 days, cell specific transcriptional profiling via single-cell RNA-sequencing was performed on isolated IFP tissue from each group. Eight transcriptomically distinct cell populations were identified within the IFP across all three treatment groups with a noted difference in the proportion of myeloid cells across the groups. Largely myeloid cells consisted of macrophages (>90%); one M1 sub-cluster highly expressing pro-inflammatory markers and two M2 sub-clusters with one of them expressing higher levels of canonical M2 markers. Notably, the diseased samples (11.9%) had the lowest proportion of cells expressing M2 markers relative to healthy (14.8%) and MSC treated (19.4%) samples. These results suggest a phenotypic polarization of IFP macrophages towards the pro-inflammatory M1 phenotype in an acute model of inflammation, which are alleviated by IFP-MSC therapy inducing a switch towards an alternate M2 status. Understanding the IFP cellular heterogeneity and associated transcriptional programs may offer insights into novel therapeutic strategies for disabling joint disease pathologies.
登录
查看更多内容
影响因子：
23.9
作者：
Caplan AI;Correa D
通讯作者：
Correa D
影响因子：
46.9
作者：
Becht, Etienne;McInnes, Leland;Newell, Evan W.
通讯作者：
Newell, Evan W.
影响因子：
9.6
作者：
Byers, Derek E.;Wu, Kangyun;Holtzman, Michael J.
通讯作者：
Holtzman, Michael J.
影响因子：
13.3
作者：
Eymard, Florent;Pigenet, Audrey;Houard, Xavier
通讯作者：
Houard, Xavier
影响因子：
3.8
作者：
Benzing, Christian;Lam, Hoyin;Wells, Claire M.
通讯作者：
Wells, Claire M.