Sphingosine-1-Phosphate Mediates Proliferation Maintaining the Multipotency of Human Adult Bone Marrow and Adipose Tissue-derived Stem Cells (Retracted article. See vol. 3, pg. 382, 2011)
Sphingosine-1-Phosphate Mediates Proliferation Maintaining the Multipotency of Human Adult Bone Marrow and Adipose Tissue-derived Stem Cells (Retracted article. See vol. 3, pg. 382, 2011)
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DOI：
10.1093/jmcb/mjq011
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发表时间：
2010-08-01
影响因子：
5.5
通讯作者：
Melendez, Alirio J.
中科院分区：
文献类型：
--
作者：
He, Xiaoli;H'ng, Shiau-Chen;Melendez, Alirio J.
高更新和维持人类成体干细胞(HSCs)的多能性是实验分析和潜在临床应用的先决条件。使用血清是目前应用最广泛的HSC培养和增殖策略。然而，血清的定义不明确，批间差异很大，这使得骨髓间充质干细胞(MSCs)在均匀培养条件下难以大规模扩增。此外，人们经常观察到，在含血清的培养液中生长的细胞会自发分化为未知和/或不想要的表型。另一种维持HSC发育的方法是使用细胞因子和/或组织特异性生长因子；这是一种非常昂贵的方法，可能会导致早期不想要的分化。为了绕过这些问题，我们研究了鞘氨醇-1-磷酸(S1P)在人骨髓和脂肪组织来源的MSCs生长和多能性维持中的作用。结果表明，S1P具有促进生长的作用，在降低血清浓度的情况下，或与生长因子成纤维细胞生长因子和血小板衍生生长因子-AB联合使用时，S1P具有促进生长的作用。我们还表明，在添加S1P的培养液中培养的MSCs能够保持其分化潜能，至少与在通常的含血清培养液中培养的细胞一样长时间。在含S1P的培养液中生长的细胞能够进行成骨和成脂分化，这表明了这一点。这一点很有意义，因为S1P是一种相对便宜的天然产品，可以在均一的高纯度批次中获得：这将最大限度地降低成本，并潜在地减少血清观察到的不必要的副作用。综上所述，S1P能够在保持不同人类干细胞的多能性的同时诱导增殖，这表明S1P在为成人干细胞培养开发无血清或无血清的限定培养液方面具有潜力。
High renewal and maintenance of multipotency of human adult stem cells (hSCs), are a prerequisite for experimental analysis as well as for potential clinical usages. The most widely used strategy for hSC culture and proliferation is using serum. However, serum is poorly defined and has a considerable degree of inter-batch variation, which makes it difficult for large-scale mesenchymal stem cells (MSCs) expansion in homogeneous culture conditions. Moreover, it is often observed that cells grown in serum-containing media spontaneously differentiate into unknown and/or undesired phenotypes. Another way of maintaining hSC development is using cytokines and/or tissue-specific growth factors; this is a very expensive approach and can lead to early unwanted differentiation. In order to circumvent these issues, we investigated the role of sphingosine-1-phosphate (S1P), in the growth and multipotency maintenance of human bone marrow and adipose tissue-derived MSCs. We show that S1P induces growth, and in combination with reduced serum, or with the growth factors FGF and platelet-derived growth factor-AB, S1P has an enhancing effect on growth. We also show that the MSCs cultured in S1P-supplemented media are able to maintain their differentiation potential for at least as long as that for cells grown in the usual serum-containing media. This is shown by the ability of cells grown in S1P-containing media to be able to undergo osteogenic as well as adipogenic differentiation. This is of interest, since S1P is a relatively inexpensive natural product, which can be obtained in homogeneous high-purity batches: this will minimize costs and potentially reduce the unwanted side effects observed with serum. Taken together, S1P is able to induce proliferation while maintaining the multipotency of different human stem cells, suggesting a potential for S1P in developing serum-free or serum-reduced defined medium for adult stem cell cultures.