Chow Rebecca P, Nguyen Kevin, Gou Wenyu, Green Erica, Morgan Katherine, Lancaster William, Helke Kristi, Strange Charlie, Wang Hongjun
Department of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA.
Department of Comparative Medicine, Medical University of South Carolina, Charleston, SC 29425, USA.
Biomedicines. 2021 Nov 16;9(11):1695. doi: 10.3390/biomedicines9111695.
Chronic pancreatitis (CP) is characterized by pancreatic inflammation, fibrosis, and abdominal pain that is challenging to treat. Mesenchymal stromal cells (MSCs) overexpressing human alpha-1 antitrypsin (hAAT-MSCs) showed improved mobility and protective functions over native MSCs in nonobese diabetic mice. We investigated whether hAAT-MSCs could mitigate CP and its associated pain using trinitrobenzene sulfonic acid (TNBS)-induced CP mouse models. CP mice were given native human MSCs or hAAT-MSCs (0.5 × 10 cells/mouse, i.v., = 6-8/group). The index of visceral pain was measured by graduated von Frey filaments. Pancreatic morphology and pancreatic mast cell count were analyzed by morphological stains. Nociceptor transient receptor potential vanilloid 1 (TRPV1) expression in dorsal root ganglia (DRG) was determined by immunohistochemistry. hAAT-MSC-treated CP mice best preserved pancreatic morphology and histology. MSC or hAAT-MSC infusion reduced abdominal pain sensitivities. hAAT-MSC therapy also suppressed TRPV1 expression in DRG and reduced pancreatic mast cell density induced by TNBS. Overall, hAAT-MSCs reduced pain and mitigated pancreatic inflammation in CP equal to MSCs with a trend toward a higher pancreatic weight and better pain relief in the hAAT-MSC group compared to the MSC group. Both MSCs and hAAT-MSCs might be used as a novel therapeutic tool for CP-related pain.
慢性胰腺炎（CP）的特征是胰腺炎症、纤维化以及难以治疗的腹痛。在非肥胖糖尿病小鼠中，过表达人α-1抗胰蛋白酶的间充质基质细胞（hAAT-MSCs）相较于天然间充质基质细胞表现出更好的迁移能力和保护功能。我们使用三硝基苯磺酸（TNBS）诱导的CP小鼠模型研究了hAAT-MSCs是否能减轻CP及其相关疼痛。给CP小鼠静脉注射天然人间充质基质细胞或hAAT-MSCs（0.5×10⁶个细胞/小鼠，每组n = 6 - 8）。通过分级的von Frey细丝测量内脏疼痛指数。通过形态学染色分析胰腺形态和胰腺肥大细胞计数。通过免疫组织化学测定背根神经节（DRG）中伤害感受器瞬时受体电位香草酸亚型1（TRPV1）的表达。hAAT-MSC治疗的CP小鼠能最好地保持胰腺形态和组织学。输注间充质基质细胞或hAAT-MSCs可降低腹部疼痛敏感性。hAAT-MSC治疗还抑制了DRG中TRPV1的表达，并降低了TNBS诱导的胰腺肥大细胞密度。总体而言，hAAT-MSCs减轻了CP中的疼痛并减轻了胰腺炎症，效果与间充质基质细胞相当，与间充质基质细胞组相比hAAT-MSC组有胰腺重量增加和疼痛缓解更好的趋势。间充质基质细胞和hAAT-MSCs都可能用作治疗CP相关疼痛的新型治疗工具。
