BOE Regenerative Medicine Technology Co., Ltd., No. 9 JiuXianQiao North Road, Beijing, 100015, China.
Heart Center, First Hospital of Tsinghua University, No. 6 JiuXianQiao 1st Road, Beijing, 10016, China.
Stem Cell Res Ther. 2022 Jun 11;13(1):252. doi: 10.1186/s13287-022-02919-8.
Human umbilical cord mesenchymal stem cells (hUC-MSCs) have been widely used due to their multipotency, a broad range of sources, painless collection, and compliance with standard amplification. Cell sheet technology is a tissue engineering methodology requiring scaffolds free, and it provides an effective method for cell transplantation. To improve the therapeutic efficacy, we combined hUC-MSCs with cell sheet technology to evaluate the safety and efficacy of hUC-MSC sheets in preclinical studies using appropriate animal models.
hUC-MSC sheets were fabricated by hUC-MSCs from a cell bank established by a standard operation process and quality control. Cytokine secretion, immunoregulation, and angiopoiesis were evaluated in vitro. Oncogenicity and cell diffusion assays of hUC-MSC sheets were conducted to verify the safety of hUC-MSCs sheet transplantation in mice. To provide more meaningful animal experimental data for clinical trials, porcine myocardial infarction (MI) models were established by constriction of the left circumflex, and hUC-MSC sheets were transplanted onto the ischemic area of the heart tissue. Cardiac function was evaluated and compared between the experimental and MI groups.
The in vitro results showed that hUC-MSC sheets could secrete multiple cellular factors, including VEGF, HGF, IL-6, and IL-8. Peripheral blood mononuclear cells had a lower proliferation rate and lower TNF-α secretion when co-cultured with hUC-MSC sheets. TH1 cells had a smaller proportion after activation. In vivo safety results showed that the hUC-MSCs sheet had no oncogenicity and was mainly distributed on the surface of the ischemic myocardial tissue. Echocardiography showed that hUC-MSC sheets effectively improved the left ventricular ejection fraction (LVEF), and the LVEF significantly changed (42.25 ± 1.23% vs. 66.9 ± 1.10%) in the hUC-MSC transplantation group compared with the MI group (42.52 ± 0.65% vs. 39.55 ± 1.97%) at 9 weeks. The infarct ratio of the hUC-MSCs sheet transplantation groups was also significantly reduced (14.2 ± 4.53% vs. 4.00 ± 2.00%) compared with that of the MI group.
Allogeneic source and cell bank established by the standard operation process and quality control make hUC-MSCs sheet possible to treat MI by off-the-shelf drug with universal quality instead of individualized medical technology.
人脐带间充质干细胞（hUC-MSCs）因其多能性、广泛的来源、无痛采集和符合标准扩增而被广泛应用。细胞片技术是一种组织工程方法，需要无支架，为细胞移植提供了一种有效的方法。为了提高治疗效果，我们将 hUC-MSCs 与细胞片技术相结合，使用适当的动物模型，在临床前研究中评估 hUC-MSC 片的安全性和有效性。
hUC-MSC 片由通过标准操作流程和质量控制建立的细胞库中的 hUC-MSCs 制成。体外评估细胞因子分泌、免疫调节和血管生成。进行 hUC-MSC 片的致癌性和细胞扩散试验，以验证 hUC-MSC 片在小鼠中的移植安全性。为了为临床试验提供更有意义的动物实验数据，通过左回旋支结扎建立猪心肌梗死（MI）模型，并将 hUC-MSC 片移植到心脏组织的缺血区域。比较实验组和 MI 组之间的心脏功能。
体外结果表明，hUC-MSC 片可分泌多种细胞因子，包括 VEGF、HGF、IL-6 和 IL-8。与 hUC-MSC 片共培养时，外周血单核细胞的增殖率较低，TNF-α分泌较低。TH1 细胞激活后比例较小。体内安全性结果表明，hUC-MSCs 片无致癌性，主要分布在缺血心肌组织表面。超声心动图显示，hUC-MSC 片有效提高了左心室射血分数（LVEF），与 MI 组（42.52±0.65%比 39.55±1.97%）相比，hUC-MSC 移植组的 LVEF 明显变化（42.25±1.23%比 66.9±1.10%）在 9 周时。hUC-MSCs 片移植组的梗死比例也明显低于 MI 组（14.2±4.53%比 4.00±2.00%）。
同种异体来源和通过标准操作流程和质量控制建立的细胞库使 hUC-MSCs 片有可能通过现成的药物治疗 MI，而不是个体化的医疗技术。
