Exosomes as biomimetic tools for stem cell differentiation: Applications in dental pulp tissue regeneration.
Exosomes as biomimetic tools for stem cell differentiation: Applications in dental pulp tissue regeneration.
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DOI：
10.1016/j.biomaterials.2016.09.029
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发表时间：
2016-12
期刊：
影响因子：
14
通讯作者：
Ravindran S
中科院分区：
文献类型：
--
作者：
Huang CC;Narayanan R;Alapati S;Ravindran S
实现和维持安全可靠的干细胞谱系特异性分化对于组织工程策略的临床转化是重要的。为了避免使用生长因子和生长因子递送系统引起的众多问题，我们探索了使用外来体作为仿生工具来诱导干细胞分化。基于细胞类型特异性exosomes可以触发干细胞的谱系特异性分化的假设，我们已经评估了来源于牙髓细胞的exosomes在生长和牙向分化条件下培养的体外和体内诱导幼稚的人牙髓干细胞（DPSC）和人骨髓源性基质细胞（HMSCs）的牙向分化的潜力。结果表明，外泌体可以结合基质蛋白，如I型胶原蛋白和纤连蛋白，使它们能够被拴系到生物材料。外泌体通过小窝内吞机制以剂量依赖性和可饱和的方式被DPSC和HMSC内吞，并触发P38丝裂原活化蛋白激酶（MAPK）途径。此外，外泌体还触发牙源性分化所需基因的表达增加。当在具有DPSC的牙根切片模型中进行体内测试时，外泌体触发了牙髓样组织的再生。然而，我们的研究结果表明，在牙源性条件下分离的外泌体是干细胞分化和组织再生的更好诱导剂。总之，我们的结果突出了潜在的外泌体作为仿生工具诱导干细胞的谱系特异性分化。我们的研究结果还表明，在选择用于治疗应用之前，考虑外泌体供体细胞的来源和状态非常重要。
Achieving and maintaining safe and reliable lineage specific differentiation of stem cells is important for clinical translation of tissue engineering strategies. In an effort to circumvent the multitude of problems arising from the usage of growth factors and growth factor delivery systems, we have explored the use of exosomes as biomimetic tools to induce stem cell differentiation. Working on the hypothesis that cell-type specific exosomes can trigger lineage-specific differentiation of stem cells, we have evaluated the potential of exosomes derived from dental pulp cells cultured on under growth and odontogenic differentiation conditions to induce odontogenic differentiation of naïve human dental pulp stem cells (DPSCs) and human bone marrow derived stromal cells (HMSCs) in vitro and in vivo. Results indicate that the exosomes can bind to matrix proteins such as type I collagen and fibronectin enabling them to be tethered to biomaterials. The exosomes are endocytosed by both DPSCs and HMSCs in a dose-dependent and saturable manner via the caveolar endocytic mechanism and trigger the P38 mitogen activated protein kinase (MAPK) pathway. In addition, the exosomes also trigger the increased expression of genes required for odontogenic differentiation. When tested in vivo in a tooth root slice model with DPSCs, the exosomes triggered regeneration of dental pulp-like tissue. However, our results indicate that exosomes isolated under odontogenic conditions are better inducers of stem cell differentiation and tissue regeneration. Overall, our results highlight the potential exosomes as biomimetic tools to induce lineage specific differentiation of stem cells. Our results also show the importance of considering the source and state of exosome donor cells before a choice is made for therapeutic applications.