Schop Deborah, Janssen Frank W, van Rijn Linda D S, Fernandes Hugo, Bloem Rolf M, de Bruijn Joost D, van Dijkhuizen-Radersma Riemke
Xpand Biotechnology BV, Bilthoven, The Netherlands.
Tissue Eng Part A. 2009 Aug;15(8):1877-86. doi: 10.1089/ten.tea.2008.0345.
Most therapeutic applications of bone marrow stromal cells (MSCs), or mesenchymal stem cells, require expansion of these cells. This study aimed to obtain more information about human MSCs regarding their expansion characteristics: growth, metabolism, and growth inhibitors. In addition, the same expansion factors were examined for (model species) goat and rat MSCs to evaluate differences between MSCs of mammalian species. MSC proliferation, nutrient consumption, and metabolite production were determined for five donors per species. In addition, the growth inhibitory concentrations of lactate and ammonia (NH3) were established. Results showed that goat MSCs grew significantly faster than human and rat MSCs and that goat cells metabolized glucose more efficiently into energy (Ylac/glc=0.8) than human (Ylac/glc=2.0) and rat MSCs (Ylac/glc=1.9). In addition, human (qGlc= -9.2pmol cell(-1) day(-1) and rat MSCs (qGlc= -5.9pmol cell(-1) day(-1)) consumed more glucose than goat MSCs (qGlc= -2.6pmol cell(-1) day(-1)). Glutamine was shown not to be important as energy source for human, goat, and rat MSCs. Regarding growth inhibition by metabolites, rat MSCs were more sensitive to lactate and NH3 (growth inhibiting at 16mM lactate and at 1.9mM NH3) than goat (lactate: 28.4mM, NH3: 2.9mM) and human MSCs (lactate: 35.4mM, NH3: 2.4mM). Human MSCs did not lose their differentiation potential when their growth was inhibited by lactate or NH3.
骨髓基质细胞（MSCs），即间充质干细胞，其大多数治疗应用都需要对这些细胞进行扩增。本研究旨在获取更多关于人MSCs扩增特性的信息：生长、代谢和生长抑制剂。此外，还对（模式物种）山羊和大鼠的MSCs检测了相同的扩增因子，以评估哺乳动物物种MSCs之间的差异。测定了每个物种五个供体的MSCs增殖、营养消耗和代谢产物生成情况。此外，还确定了乳酸和氨（NH3）的生长抑制浓度。结果表明，山羊MSCs的生长速度明显快于人和大鼠的MSCs，并且山羊细胞将葡萄糖更有效地代谢为能量（Ylac/glc = 0.8），而人（Ylac/glc = 2.0）和大鼠MSCs（Ylac/glc = 1.9）则不然。此外，人（qGlc = -9.2pmol细胞⁻¹天⁻¹）和大鼠MSCs（qGlc = -5.9pmol细胞⁻¹天⁻¹）比山羊MSCs（qGlc = -2.6pmol细胞⁻¹天⁻¹）消耗更多的葡萄糖。谷氨酰胺对人、山羊和大鼠的MSCs而言并非重要的能量来源。关于代谢产物对生长的抑制作用，大鼠MSCs比山羊（乳酸：28.4mM，氨：2.9mM）和人MSCs（乳酸：35.4mM，氨：2.4mM）对乳酸和NH3更敏感（在乳酸浓度为16mM和氨浓度为1.9mM时生长受到抑制）。当人MSCs的生长受到乳酸或NH3抑制时，它们并未丧失分化潜能。
