Department of Biomedical Science, College of Life Sciences, CHA University, Seongnam 13496, Republic of Korea.
ATEMs Inc., Seoul 02447, Republic of Korea.
Int J Mol Sci. 2023 Feb 5;24(4):3146. doi: 10.3390/ijms24043146.
Lower back pain is a major problem caused by intervertebral disc degeneration. A common surgical procedure is lumbar partial discectomy (excision of the herniated disc causing nerve root compression), which results in further disc degeneration, severe lower back pain, and disability after discectomy. Thus, the development of disc regenerative therapies for patients who require lumbar partial discectomy is crucial. Here, we investigated the effectiveness of an engineered cartilage gel utilizing human fetal cartilage-derived progenitor cells (hFCPCs) on intervertebral disc repair in a rat tail nucleotomy model. Eight-week-old female Sprague-Dawley rats were randomized into three groups to undergo intradiscal injection of (1) cartilage gel, (2) hFCPCs, or (3) decellularized extracellular matrix (ECM) ( = 10/each group). The treatment materials were injected immediately after nucleotomy of the coccygeal discs. The coccygeal discs were removed six weeks after implantation for radiologic and histological analysis. Implantation of the cartilage gel promoted degenerative disc repair compared to hFCPCs or hFCPC-derived ECM by increasing the cellularity and matrix integrity, promoting reconstruction of nucleus pulposus, restoring disc hydration, and downregulating inflammatory cytokines and pain. Our results demonstrate that cartilage gel has higher therapeutic potential than its cellular or ECM component alone, and support further translation to large animal models and human subjects.
下腰痛是由椎间盘退变引起的主要问题。一种常见的手术方法是腰椎部分切除术(切除导致神经根受压的椎间盘突出),这会导致进一步的椎间盘退变、严重的下腰痛以及椎间盘切除术后的残疾。因此,为需要腰椎部分切除术的患者开发椎间盘再生疗法至关重要。在这里,我们研究了利用人胎儿软骨源性祖细胞(hFCPC)的工程软骨凝胶在大鼠尾核切除模型中对椎间盘修复的有效性。将 8 周龄雌性 Sprague-Dawley 大鼠随机分为三组,分别接受椎间盘内注射(1)软骨凝胶、(2)hFCPCs 或(3)去细胞细胞外基质(ECM)(每组=10)。在尾骨椎间盘核切除术后立即注射治疗材料。植入 6 周后取出尾骨椎间盘进行放射学和组织学分析。与 hFCPCs 或 hFCPC 衍生的 ECM 相比,软骨凝胶通过增加细胞密度和基质完整性、促进髓核重建、恢复椎间盘水合作用以及下调炎症细胞因子和疼痛来促进退行性椎间盘修复。我们的结果表明,软骨凝胶比其细胞或 ECM 成分单独具有更高的治疗潜力,并支持进一步转化为大型动物模型和人体。