Assis-Ribas Thais, Forni Maria Fernanda, Winnischofer Sheila Maria Brochado, Sogayar Mari Cleide, Trombetta-Lima Marina
NUCEL-NETCEM-Faculdade de Medicina, Departamento de Clínica Médica, Universidade de São Paulo, São Paulo, SP 05360-120, Brazil.
Instituto de Química, Departamento de Bioquímica, Universidade de São Paulo, São Paulo, SP 05508-000, Brazil.
Dev Biol. 2018 May 15;437(2):63-74. doi: 10.1016/j.ydbio.2018.03.002. Epub 2018 Mar 12.
Mesenchymal stem cells (MSCs) are stromal cells that display self-renewal and multipotent differentiation capacity. The repertoire of mature cells generated ranges but is not restricted to: fat, bone and cartilage. Their potential importance for both cell therapy and maintenance of in vivo homeostasis is indisputable. Nonetheless, both their in vivo identity and use in cell therapy remain elusive. A drawback generated by this fact is that little is known about the MSC niche and how it impacts differentiation and homeostasis maintenance. Hence, the roles played by the extracellular matrix (ECM) and its main regulators namely: the Matrix Metalloproteinases (MMPs) and their counteracting inhibitors (TIMPs and RECK) upon stem cells differentiation are only now beginning to be unveiled. Here, we will focus on mesenchymal stem cells and review the main mechanisms involved in adipo, chondro and osteogenesis, discussing how the extracellular matrix can impact not only lineage commitment, but, also, their survival and potentiality. This review critically analyzes recent work in the field in an effort towards a better understanding of the roles of Matrix Metalloproteinases and their inhibitors in the above-cited events.
间充质干细胞（MSCs）是具有自我更新和多能分化能力的基质细胞。其分化产生的成熟细胞种类多样，但不限于：脂肪、骨和软骨。它们在细胞治疗和体内稳态维持方面的潜在重要性是无可争议的。然而，它们在体内的身份以及在细胞治疗中的应用仍然难以捉摸。由此产生的一个缺点是，人们对MSC微环境及其如何影响分化和稳态维持知之甚少。因此，细胞外基质（ECM）及其主要调节因子，即基质金属蛋白酶（MMPs）及其拮抗抑制剂（TIMPs和RECK）在干细胞分化过程中所起的作用，直到现在才开始被揭示。在这里，我们将聚焦于间充质干细胞，回顾脂肪生成、软骨生成和成骨过程中涉及的主要机制，讨论细胞外基质如何不仅影响细胞谱系定向，还影响它们的存活和潜能。这篇综述批判性地分析了该领域的最新研究工作，以期更好地理解基质金属蛋白酶及其抑制剂在上述事件中的作用。
