Koivunotko Elle, Snirvi Jasmi, Merivaara Arto, Harjumäki Riina, Rautiainen Swarna, Kelloniemi Minna, Kuismanen Kirsi, Miettinen Susanna, Yliperttula Marjo, Koivuniemi Raili
Drug Research Program, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, 00790 Helsinki, Finland.
Department of Plastic and Reconstructive Surgery, Tampere University Hospital, 33520 Tampere, Finland.
Biomedicines. 2022 Oct 15;10(10):2584. doi: 10.3390/biomedicines10102584.
Adipose-derived mesenchymal stromal cells (ASCs) hold great potential for cellular therapies by having immunomodulatory behavior and tissue regenerative properties. Due to the capability of ASCs to differentiate into endothelial cells (ECs) and other angiogenic cell types, such as pericytes, ASCs are a highly valuable source for stimulating angiogenesis. However, cellular therapies in tissue engineering have faced challenges in poor survival of the cells after transplantation, which is why a protective biomaterial scaffold is required. In this work, we studied the potential of nanofibrillated cellulose (NFC) hydrogel to be utilized as a suitable matrix for three-dimensional (3D) cell culturing of human-derived ASCs (hASCs) and studied their angiogenic properties and differentiation potential in ECs and pericytes. In addition, we tested the effect of hASC-conditioned medium and stimulation with angiopoietin-1 (Ang-1) on human umbilical vein endothelial cells (HUVECs) to induce blood vessel-type tube formation in NFC hydrogel. The hASCs were successfully 3D cell cultured in NFC hydrogel as they formed spheroids and had high cell viability with angiogenic features. Most importantly, they showed angiogenic potential by having pericyte-like characteristics when differentiated in EC medium, and their conditioned medium improved HUVEC viability and tube formation, which recalls the active paracrine properties. This study recommends NFC hydrogel for future use as an animal-free biomaterial scaffold for hASCs in therapeutic angiogenesis and other cell therapy purposes.
脂肪来源的间充质基质细胞（ASCs）具有免疫调节行为和组织再生特性，在细胞治疗方面具有巨大潜力。由于ASCs能够分化为内皮细胞（ECs）和其他血管生成细胞类型，如周细胞，因此ASCs是刺激血管生成的极有价值的来源。然而，组织工程中的细胞治疗面临着移植后细胞存活率低的挑战，这就是需要保护性生物材料支架的原因。在这项工作中，我们研究了纳米原纤化纤维素（NFC）水凝胶作为人源ASCs（hASCs）三维（3D）细胞培养合适基质的潜力，并研究了它们在ECs和周细胞中的血管生成特性和分化潜力。此外，我们测试了hASC条件培养基和血管生成素-1（Ang-1）刺激对人脐静脉内皮细胞（HUVECs）在NFC水凝胶中诱导血管样管形成的影响。hASCs在NFC水凝胶中成功进行了3D细胞培养，因为它们形成了球体，具有高细胞活力并具有血管生成特征。最重要的是，当在EC培养基中分化时，它们通过具有周细胞样特征显示出血管生成潜力，并且它们的条件培养基提高了HUVEC的活力和管形成，这让人想起其活跃的旁分泌特性。本研究推荐NFC水凝胶在未来用作无动物生物材料支架，用于hASCs的治疗性血管生成和其他细胞治疗目的。
