Arun Manorathna, Rajasingh Sheeja, Madasamy Parani, Rajasingh Johnson
Department of Genetic Engineering, School of Bio-Engineering, SRM Institute of Science and Technology, Kattankulathur, Chengalpattu 603203, Tamil Nadu, India.
Department of Bioscience Research, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Bioengineering (Basel). 2025 Aug 5;12(8):844. doi: 10.3390/bioengineering12080844.
Bone integrity is maintained through continuous remodeling, orchestrated by the coordinated actions of osteocytes, osteoblasts, and osteoclasts. Once considered passive bystanders, osteocytes are now recognized as central regulators of this process, mediating biochemical signaling and mechanotransduction. Malfunctioning osteocytes contribute to serious skeletal disorders such as osteoporosis. Mesenchymal stromal cells (MSCs), multipotent stem cells capable of differentiating into osteoblasts, have emerged as promising agents for bone regeneration, primarily through the paracrine effects of their secreted exosomes. MSC-derived exosomes are nanoscale vesicles enriched with proteins, lipids, and nucleic acids that promote intercellular communication, osteoblast proliferation and differentiation, and angiogenesis. Notably, they deliver osteoinductive microRNAs (miRNAs) that influence osteogenic markers and support bone tissue repair. In vivo investigations validate their capacity to enhance bone regeneration, increase bone volume, and improve biomechanical strength. Additionally, MSC-derived exosomes regulate the immune response, creating pro-osteogenic and pro-angiogenic factors, boosting their therapeutic efficacy. Due to their cell-free characteristics, MSC-derived exosomes offer benefits such as diminished immunogenicity and minimal risk of off-target effects. These properties position them as promising and innovative approaches for bone regeneration, integrating immunomodulatory effects with tissue-specific regenerative capabilities.
骨完整性通过由骨细胞、成骨细胞和破骨细胞的协同作用精心编排的持续重塑得以维持。骨细胞曾被视为被动旁观者,如今被公认为这一过程的核心调节因子,介导生化信号传导和机械转导。功能失调的骨细胞会导致诸如骨质疏松症等严重的骨骼疾病。间充质基质细胞(MSCs)是能够分化为成骨细胞的多能干细胞,已成为骨再生的有前景的介质,主要是通过其分泌的外泌体的旁分泌作用。源自MSCs的外泌体是富含蛋白质、脂质和核酸的纳米级囊泡,可促进细胞间通讯、成骨细胞增殖和分化以及血管生成。值得注意的是,它们递送影响成骨标志物并支持骨组织修复的骨诱导性微小RNA(miRNAs)。体内研究证实了它们增强骨再生、增加骨体积和改善生物力学强度的能力。此外,源自MSCs的外泌体调节免疫反应,产生促骨生成和促血管生成因子,提高其治疗效果。由于其无细胞特性,源自MSCs的外泌体具有诸如降低免疫原性和最小脱靶效应风险等优点。这些特性使其成为骨再生的有前景和创新性方法,将免疫调节作用与组织特异性再生能力相结合。