Otsuka Takayoshi, Mengsteab Paulos Y, Laurencin Cato T
Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health, Farmington, CT 06030, USA; Raymond and Beverly Sackler Center for Biological, Physical and Engineering Sciences, University of Connecticut Health, CT 06030, USA; Department of Orthopedic Surgery, University of Connecticut Health, Farmington, CT 06030, USA.
Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health, Farmington, CT 06030, USA; Raymond and Beverly Sackler Center for Biological, Physical and Engineering Sciences, University of Connecticut Health, CT 06030, USA; Department of Orthopedic Surgery, University of Connecticut Health, Farmington, CT 06030, USA; Department of Biomedical Engineering, University of Connecticut, Storrs, CT 06269, USA.
Stem Cell Res. 2021 Mar;51:102155. doi: 10.1016/j.scr.2021.102155. Epub 2021 Jan 7.
In order to develop strategies to regenerate complex tissues in mammals, understanding the role of signaling in regeneration competent species and mammalian development is of critical importance. Fibroblast growth factor 8 (FGF-8) signaling has an essential role in limb morphogenesis and blastema outgrowth. Therefore, we aimed to study the effect of FGF-8b on the proliferation and differentiation of mesenchymal stem cells (MSCs), which have tremendous potential for therapeutic use of cell-based therapy. Rat adipose derived stem cells (ADSCs) and muscle progenitor cells (MPCs) were isolated and cultured in growth medium and various types of differentiation medium (osteogenic, chondrogenic, adipogenic, tenogenic, and myogenic medium) with or without FGF-8b supplementation. We found that FGF-8b induced robust proliferation regardless of culture medium. Genes related to limb development were upregulated in ADSCs by FGF-8b supplementation. Moreover, FGF-8b enhanced chondrogenic differentiation and suppressed adipogenic and tenogenic differentiation in ADSCs. Osteogenic differentiation was not affected by FGF-8b supplementation. FGF-8b was found to enhance myofiber formation in rat MPCs. Overall, this study provides foundational knowledge on the effect of FGF-8b in the proliferation and fate determination of MSCs and provides insight in its potential efficacy for musculoskeletal therapies.
为了制定在哺乳动物中再生复杂组织的策略，了解信号传导在具备再生能力的物种和哺乳动物发育中的作用至关重要。成纤维细胞生长因子8（FGF - 8）信号传导在肢体形态发生和芽基生长中起着至关重要的作用。因此，我们旨在研究FGF - 8b对间充质干细胞（MSC）增殖和分化的影响，间充质干细胞在基于细胞的治疗中具有巨大的治疗应用潜力。分离大鼠脂肪来源干细胞（ADSC）和肌肉祖细胞（MPC），并在生长培养基以及添加或不添加FGF - 8b的各种类型分化培养基（成骨、成软骨、成脂、成腱和生肌培养基）中培养。我们发现，无论培养基如何，FGF - 8b均可诱导强劲的增殖。通过添加FGF - 8b，ADSC中与肢体发育相关的基因上调。此外，FGF - 8b增强了ADSC的成软骨分化，并抑制了其成脂和成腱分化。成骨分化不受添加FGF - 8b的影响。研究发现FGF - 8b可增强大鼠MPC中的肌纤维形成。总体而言，本研究提供了关于FGF - 8b对MSC增殖和命运决定影响的基础知识，并深入了解了其在肌肉骨骼治疗中的潜在疗效。
