Brozovich Ava A, Lenna Stefania, Paradiso Francesca, Serpelloni Stefano, McCulloch Patrick, Weiner Bradley, Yustein Jason T, Taraballi Francesca
Texas A&M College of Medicine, Bryan, TX, USA.
Center for Musculoskeletal Regeneration, Houston Methodist Research Institute, Houston, TX, USA.
J Tissue Eng. 2022 Nov 25;13:20417314221138945. doi: 10.1177/20417314221138945. eCollection 2022 Jan-Dec.
Osteosarcoma (OS) is the most common bone tumor in pediatrics. After resection, allografts or metal endoprostheses reconstruct bone voids, and systemic chemotherapy is used to prevent recurrence. This urges the development of novel treatment options for the regeneration of bone after excision. We utilized a previously developed biomimetic, biodegradable magnesium-doped hydroxyapatite/type I collagen composite material (MHA/Coll) to promote bone regeneration in the presence of chemotherapy. We also performed experiments to determine if human mesenchymal stem cells (hMSCs) seeded on MHA/Coll scaffold migrate less toward OS cells, suggesting that hMSCs will not contribute to tumor growth and therefore the potential of oncologic safety in vitro. Also, hMSCs seeded on MHA/Coll had increased expression of osteogenic genes () compared to hMSCs in the 2D condition, even when exposed to chemotherapeutics. This is the first study to demonstrate that a highly osteogenic scaffold can potentially be oncologically safe because hMSCs on MHA/Coll tend to differentiate and lose the ability to migrate toward tumor cells. Therefore, hMSCs on MHA/Coll could potentially be utilized for bone regeneration after OS excision.
骨肉瘤(OS)是儿科最常见的骨肿瘤。切除术后,同种异体移植物或金属内置假体用于重建骨缺损,同时采用全身化疗预防复发。这促使人们开发新的治疗方法以促进切除术后骨的再生。我们利用先前开发的仿生、可生物降解的镁掺杂羟基磷灰石/ I型胶原复合材料(MHA/Coll)在化疗存在的情况下促进骨再生。我们还进行了实验,以确定接种在MHA/Coll支架上的人间充质干细胞(hMSCs)向OS细胞的迁移是否减少,这表明hMSCs不会促进肿瘤生长,因此在体外具有肿瘤学安全性的潜力。此外,与二维条件下的hMSCs相比,接种在MHA/Coll上的hMSCs即使在接触化疗药物时,其成骨基因的表达也有所增加。这是第一项证明高度成骨的支架可能具有肿瘤学安全性的研究,因为MHA/Coll上的hMSCs倾向于分化并失去向肿瘤细胞迁移的能力。因此,MHA/Coll上的hMSCs有可能用于骨肉瘤切除术后的骨再生。