Paresishvili Teona, Janelidze Merab, Kakabadze Zurab
Department of Clinical Anatomy, Tbilisi State Medical University Tbilisi 0186, Georgia.
Am J Cancer Res. 2023 Jun 15;13(6):2504-2516. eCollection 2023.
In this study, we present a multifunctional hybrid hydrogel (MFHH) for the prevention of postoperative tumor recurrence. MFHH consists of two components; component A - containing a gelatin-based cisplatin, which destroys the residual cancer after surgery, and component B - containing macroporous gelatin microcarriers (CultiSpher) loaded with freeze-dried bone marrow stem cells (BMSCs), which activates the wound healing process. We also evaluated the effects of MFHH in a subcutaneous Ehrlich tumor mouse model. MFHH acted as a local delivery system by directly supplying cisplatin to the tumor environment, resulting in excellent anti-cancer effects and minimal side effects. MFHH released cisplatin gradually to destroy the residual tumors, thereby preventing loco-regional recurrence. We have also demonstrated that BMSCs are able to inhibit residual tumor growth. Moreover, CultiSpher loaded with BMSCs acted as an injection 3D scaffold and easily filled the wound defect formed by tumor removal, and the paracrine factors of the freeze-dried BMSCs accelerated the wound healing process. The components of the MFHH can be used both separately and together. However, for the successful application of MFHH in clinical practice, it is necessary to study in more detail the role of paracrine factors of freeze-dried BMSCs in the inhibition or proliferation of residual cancer. These questions will be the focus of our future research.
在本研究中，我们展示了一种用于预防术后肿瘤复发的多功能混合水凝胶（MFHH）。MFHH由两个成分组成；成分A含有基于明胶的顺铂，可在手术后破坏残留癌细胞，成分B含有负载冻干骨髓干细胞（BMSC）的大孔明胶微载体（CultiSpher），可激活伤口愈合过程。我们还在皮下艾氏肿瘤小鼠模型中评估了MFHH的效果。MFHH通过直接向肿瘤环境供应顺铂，作为一种局部递送系统，产生了优异的抗癌效果且副作用最小。MFHH逐渐释放顺铂以破坏残留肿瘤，从而防止局部复发。我们还证明了BMSC能够抑制残留肿瘤生长。此外，负载BMSC的CultiSpher作为一种注射用3D支架，能够轻松填充肿瘤切除后形成的伤口缺损，并且冻干BMSC的旁分泌因子加速了伤口愈合过程。MFHH的成分可以单独使用，也可以一起使用。然而，为了MFHH在临床实践中的成功应用，有必要更详细地研究冻干BMSC的旁分泌因子在抑制或残留癌细胞增殖中的作用。这些问题将是我们未来研究的重点。
