Bertone Alicia L, Reinemeyer Craig, Tsaprailis George, Ragland Daniel, Leise Britta
Department of Veterinary Clinical Sciences (Emeritus), The Ohio State University, 1900 Coffey Rd, Columbus, OH, 43210, USA.
East Tennessee Clinical Research, Inc, 80 Copper Ridge Farm Rd, Rockwood, TN, 37854, USA.
BMC Med. 2025 Jul 23;23(1):439. doi: 10.1186/s12916-025-04231-7.
The use of micro-particulate allografts is rising, but knowledge about the protein characterization and biocompatibility of umbilical cord-derived allografts (UC) in vivo is limited.
Proteomic analyses using mass spectrometry (MS) determined equine UC protein relative quantification and functions using total spectral counts (TSC). UC cytokines were quantified by enzyme-linked immunosorbent assay (ELISA). Three in vivo studies assessed recipient clinical and tissue biocompatibility in joints and ligaments.
Proteomics revealed 2645 annotated TSCs. Proteins of > 89 TSC were considered abundant and were present in all donors. Proteins within the same donor had a 4.7% mean variation. Inflammatory cytokines were low in UC. In vivo, the prospective randomized, masked, controlled study in carpal joints and ligaments of clinically normal horses had median scores of 0 (none) for lameness and pain for 42 days. Synovial fluid showed a transient transudative synovitis after UC injection that was greater than baseline and control and returned to normal after day 5 (P < 0.001). Synovial fluid inflammatory cytokines were low; however, the anti-inflammatory cytokines Il-1ra, Il-10, and Il-1ra/Il-1 ratio were greater after UC injection than at baseline and control (P < 0.001). Blood hematology, chemistries, and serum amyloid A did not reveal systemic effects. The in vivo study of osteoarthritis and desmitis/tendonitis improved in lameness and pain over a 28-day study and had parallel synovial fluid results to the normal horse study, also without adverse events. The in vivo pathologic study evaluated joint and ligament tissues 2 and 5 days after injection and corresponding lymph nodes for evidence of the allograft or inflammation. The synovial membrane, articular cartilage, and lymph nodes were histologically normal, except for mild inflammation in the injection tracts.
Well-defined proteins were consistently present in different donors and within batches. Proteins included fibrillar and glycan proteins with a variety of roles and regulatory functions in the connective tissue matrix. The rise in Il-1ra and high Il-1ra/Il-1 ratio after UC injection could block the catabolic effect of Il-1. No adverse events were observed. Within the limits of this study, UC was safe for injection into joints and ligaments in clinically normal horses.
微颗粒同种异体移植物的使用正在增加，但关于脐带来源的同种异体移植物（UC）在体内的蛋白质特性和生物相容性的知识有限。
使用质谱（MS）进行蛋白质组学分析，通过总光谱计数（TSC）确定马UC蛋白质的相对定量和功能。通过酶联免疫吸附测定（ELISA）对UC细胞因子进行定量。三项体内研究评估了受体在关节和韧带中的临床和组织生物相容性。
蛋白质组学揭示了2645个注释的TSC。TSC大于89的蛋白质被认为是丰富的，并且在所有供体中都存在。同一供体内的蛋白质平均变异率为4.7%。UC中的炎性细胞因子含量较低。在体内，对临床正常马匹的腕关节和韧带进行的前瞻性随机、盲法、对照研究中，跛行和疼痛的中位数评分在42天内为0（无）。注射UC后，滑液显示出短暂的渗出性滑膜炎，其程度高于基线和对照组，并在第5天后恢复正常（P<0.001）。滑液中的炎性细胞因子含量较低；然而，注射UC后，抗炎细胞因子Il-1ra、Il-10和Il-1ra/Il-1比值高于基线和对照组（P<0.001）。血液血液学、化学指标和血清淀粉样蛋白A未显示出全身影响。骨关节炎和肌腱炎/腱鞘炎的体内研究在28天的研究中跛行和疼痛有所改善，滑液结果与正常马匹研究相似，也未出现不良事件。体内病理学研究在注射后2天和5天评估关节和韧带组织以及相应的淋巴结，以寻找同种异体移植物或炎症的证据。除注射部位有轻度炎症外，滑膜、关节软骨和淋巴结组织学正常。
不同供体和批次中始终存在明确的蛋白质。这些蛋白质包括在结缔组织基质中具有多种作用和调节功能的纤维状和聚糖蛋白。注射UC后Il-1ra升高以及高Il-1ra/Il-1比值可阻断Il-1的分解代谢作用。未观察到不良事件。在本研究的范围内，UC注射到临床正常马匹的关节和韧带中是安全的。
