Department of Surgical and Radiological Sciences, University of California, One Shields Avenue, Davis, CA, 95616, USA.
Veterinary Institute for Regenerative Cures, School of Veterinary Medicine, University of California, Davis, CA, 95616, USA.
Stem Cell Res Ther. 2020 Mar 13;11(1):115. doi: 10.1186/s13287-020-01623-9.
The ability of mesenchymal stem cells (MSCs) to modulate immune responses inspired a series of clinical trials addressing oral mucosal inflammation. We previously reported on the safety and efficacy of fresh, allogeneic and autologous, adipose-derived mesenchymal stem cells (ASCs) to treat feline gingivostomatitis (FCGS), an oral mucosal inflammatory disease that shares similarities with human oral lichen planus.
To meet clinical demand and goals for future commercialization, we determined the feasibility of shipping fresh ASCs to distant clinics and extended our pilot studies to expand safety and efficacy data for shipped and non-shipped ASCs in a cohort of 18 FCGS cats enrolled locally and at a few different locations within the USA.
We found that ASCs retained their viability, phenotype, and function after shipment. ASCs administered systemically resulted in a 72% positive response rate, identical to that noted in our previous studies. Cats that responded to ASC therapy had a significant decrease in circulating globulin concentration and histological evidence of decreased CD3+ T cells and CD20+ B cells in the oral mucosa. Responder cats also had significantly decreased percentages of CD8 cells in blood prior to and at 3 months post-ASC therapy. CD8 cells may serve as a potential "predictor" for response to systemic ASC therapy.
Fresh feline ASCs can be successfully shipped and administered to cats with FCGS. ASCs modulate the immune response and demonstrate efficacy for chronic oral mucosal inflammatory lesions that are characterized by CD8+ T cell inflammation and T cell activation. FCGS is a potentially useful naturally occurring large animal model of human oral inflammatory diseases.
间充质干细胞（MSCs）调节免疫反应的能力激发了一系列针对口腔黏膜炎症的临床试验。我们之前报道过新鲜同种异体和自体脂肪来源间充质干细胞（ASCs）治疗猫牙龈炎（FCGS）的安全性和有效性，FCGS 是一种口腔黏膜炎症性疾病，与人类口腔扁平苔藓有相似之处。
为了满足临床需求和未来商业化的目标，我们确定了将新鲜 ASC 运往偏远诊所的可行性，并在一组 18 只 FCGS 猫中扩大了我们的试点研究，以扩大已发货和未发货 ASC 的安全性和有效性数据，这些猫是在当地和美国的几个不同地点招募的。
我们发现 ASC 运输后仍保持其活力、表型和功能。系统给予 ASC 后，有 72%的猫出现阳性反应率，与我们之前的研究结果相同。对 ASC 治疗有反应的猫的循环球蛋白浓度显著降低，口腔黏膜中 CD3+T 细胞和 CD20+B 细胞的组织学证据减少。 responder 猫在 ASC 治疗前和治疗后 3 个月的血液中 CD8 细胞的百分比也显著降低。CD8 细胞可能是对全身 ASC 治疗反应的潜在“预测因子”。
新鲜的猫 ASC 可以成功地运往 FCGS 猫，并进行给药。ASCs 调节免疫反应，并对以 CD8+T 细胞炎症和 T 细胞激活为特征的慢性口腔黏膜炎症性病变显示出疗效。FCGS 是一种潜在有用的人类口腔炎症性疾病的大型动物自然发生模型。
