Jin Minki, Kim Bo Seok, Seo Sung Ho, Kim Minjeong, Kang Yun Gyeong, Shin Jung-Woog, Cho Kwan Hyung, Shin Meong Cheol, Yoon Changhan, Min Kyoung Ah
College of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje University, 197 Injero, Gimhae, Gyeongnam 50834, Korea.
College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, Korea.
Pharmaceutics. 2021 Mar 27;13(4):457. doi: 10.3390/pharmaceutics13040457.
Mesenchymal stem cells (MSCs) have been extensively used in the tissue regeneration therapy. Ex vivo therapy with well-differentiated osteogenic cells is known as an efficient treatment for musculoskeletal diseases, including rheumatoid diseases. However, along with its high cost, the current therapy has limitations in terms of restoring bone regeneration procedures. An efficient process for the cell differentiation to obtain a large number of functionalized osteogenic cells is necessary. Therefore, it is strongly recommended to develop strategies to produce sufficient numbers of well-differentiated osteogenic cells from the MSCs. In general, differentiation media with growth factors have been used to facilitate cell differentiation. In the present study, the poly (lactic-co-glycolic acid) (PLGA) nanoparticles incorporating the growth factors were included in the media, resulting in releasing growth factors (dexamethasone and β-glycerophosphate) in the media in the controlled manner. Stable growth and early differentiation of osteogenic cells were achieved by the PLGA-based growth factor releasing system. Moreover, low intensity pulsed ultrasound was applied to this system to induce cell differentiation process. The results revealed that, as a biomarker at early stage of osteogenic cell differentiation, Lamin A/C nuclear protein was efficiently expressed in the cells growing in the presence of PLGA-based growth factor reservoirs and ultrasound. In conclusion, our results showed that the ultrasound stimulation combined with polymeric nanoparticles releasing growth factors could potentially induce osteogenic cell differentiation.
间充质干细胞（MSCs）已被广泛应用于组织再生治疗。用充分分化的成骨细胞进行体外治疗是治疗肌肉骨骼疾病（包括类风湿疾病）的一种有效方法。然而，除了成本高昂外，目前的治疗方法在恢复骨再生过程方面存在局限性。因此，需要一个有效的细胞分化过程来获得大量功能化的成骨细胞。所以，强烈建议制定策略，从间充质干细胞中产生足够数量的充分分化的成骨细胞。一般来说，含有生长因子的分化培养基已被用于促进细胞分化。在本研究中，含有生长因子的聚（乳酸-乙醇酸）（PLGA）纳米颗粒被添加到培养基中，从而使生长因子（地塞米松和β-甘油磷酸）以可控的方式在培养基中释放。基于PLGA的生长因子释放系统实现了成骨细胞的稳定生长和早期分化。此外，对该系统施加低强度脉冲超声以诱导细胞分化过程。结果显示，作为成骨细胞分化早期阶段的生物标志物，核纤层蛋白A/C在存在基于PLGA的生长因子储库和超声的情况下生长的细胞中高效表达。总之，我们的结果表明，超声刺激与释放生长因子的聚合物纳米颗粒相结合可能会诱导成骨细胞分化。
