Ossanna Riccardo, Quintero Sierra Lindsey Alejandra, Ghazanfar Tehrani Sara, Jha Vivekanand, Curatola Chiara, Busato Alice, Conti Anita, Conti Giamaica, Zingaretti Nicola, Parodi Pier Camillo, De Francesco Francesco, Riccio Michele, Sbarbati Andrea
Department of Neuroscience, Biomedicine, and Movement, Section of Anatomy and Histology, University of Verona, Verona, Italy.
Aptuit and Evotec Company, Safety and Assessment Department, Verona, Italy.
Front Cell Dev Biol. 2025 May 13;13:1582083. doi: 10.3389/fcell.2025.1582083. eCollection 2025.
The stromal vascular fraction (SVF) is a complex and heterogeneous suspension derived from adipose tissue, containing both cellular and noncellular components. Its cellular fraction includes adipose-derived stem cells (ASCs), endothelial precursor cells, pericytes, macrophages, lymphocytes, and smooth muscle cells. The acellular "secretome" of SVF includes bioactive molecules such as growth factors, cytokines, chemokines, extracellular vesicles, and fragments of extracellular matrix (ECM), which contribute to its regenerative potential. Bone defeatures can be stimulated by mesenchymal stem cells (MSCs) that differentiate into osteoblast to support the healing and repair process. In addition to its cell content, the SVF is rich in growth factors, cytokines and chemokines, extracellular vesicles, and extracellular matrix components, which could stimulate regenerative processes through a trophic effect. Studies showed that hyaluronic acids are usually involved in healing processes. This study was focused on the healing potency of stromal stem cells isolated from adipose tissues by mechanical digestion, and the role of low-molecular-weight hyaluronic acid (LMW-HA, ACP) in the healing process was tested in calvarial defeatures in a mouse model, in comparison with the enzymatic digestion method.
The bone healing and remodeling process was evaluated using magnetic resonance imaging (MRI) up to 15 days post-treatment, and differences in the quality of bone regeneration were assessed by histological analysis, immunofluorescences, and ultrastructural analysis. The bone matrix formed after treatment with mechanically digested Hy tissue stromal vascular fraction + hyaluronic acid (HT-SVF + ACP) was compared to that formed with enzymatically digested stromal vascular fraction + hyaluronic acid (ED-SVF + ACP), with the saline group serving as the control group.
In this study, we explore a groundbreaking approach using HT-SVF combined with ACP to promote bone regeneration. Through comparative analysis with ED-SVF in a calvarial defect mouse model, we demonstrate the superior efficacy of HT-SVF + ACP in enhancing bone healing, reducing fibrotic tissue, and improving bone matrix maturity.
The findings establish the potential of HT-SVF as a cost-effective and efficient method for bone regenerative therapy.
基质血管组分（SVF）是一种源自脂肪组织的复杂且异质性的混悬液，包含细胞和非细胞成分。其细胞成分包括脂肪来源干细胞（ASC）、内皮祖细胞、周细胞、巨噬细胞、淋巴细胞和平滑肌细胞。SVF的无细胞“分泌组”包括生物活性分子，如生长因子、细胞因子、趋化因子、细胞外囊泡和细胞外基质（ECM）片段，这些有助于其再生潜能。间充质干细胞（MSC）分化为成骨细胞可刺激骨缺损修复，以支持愈合和修复过程。除了其细胞成分外，SVF富含生长因子、细胞因子、趋化因子、细胞外囊泡和细胞外基质成分，它们可通过营养作用刺激再生过程。研究表明，透明质酸通常参与愈合过程。本研究聚焦于通过机械消化从脂肪组织中分离的基质干细胞的愈合能力，并在小鼠颅骨缺损模型中测试低分子量透明质酸（LMW-HA，ACP）在愈合过程中的作用，同时与酶消化法进行比较。
在治疗后长达15天使用磁共振成像（MRI）评估骨愈合和重塑过程，并通过组织学分析、免疫荧光和超微结构分析评估骨再生质量的差异。将机械消化的Hy组织基质血管组分+透明质酸（HT-SVF+ACP）处理后形成的骨基质与酶消化的基质血管组分+透明质酸（ED-SVF+ACP）处理后形成的骨基质进行比较，生理盐水组作为对照组。
在本研究中，我们探索了一种使用HT-SVF联合ACP促进骨再生的开创性方法。通过在颅骨缺损小鼠模型中与ED-SVF进行比较分析，我们证明了HT-SVF+ACP在增强骨愈合、减少纤维化组织和改善骨基质成熟度方面具有更高的疗效。
这些发现确立了HT-SVF作为一种具有成本效益且高效的骨再生治疗方法的潜力。
