Pisati Federica, Bossolasco Patrizia, Meregalli Mirella, Cova Lidia, Belicchi Marzia, Gavina Manuela, Marchesi Chiara, Calzarossa Cinzia, Soligo Davide, Lambertenghi-Deliliers Giorgio, Bresolin Nereo, Silani Vincenzo, Torrente Yvan, Polli Elio
Fondazione IRCCS Ospedale Maggiore, Department of Neurological Sciences, Stem Cell Laboratory, Dino Ferrari Center, University of Milan, Milan, Italy.
Cell Transplant. 2007;16(1):41-55. doi: 10.3727/000000007783464443.
In animal models of neurological disorders for cerebral ischemia, Parkinson's disease, and spinal cord lesions, transplantation of mesenchymal stem cells (MSCs) has been reported to improve functional outcome. Three mechanisms have been suggested for the effects of the MSCs: transdifferentiation of the grafted cells with replacement of degenerating neural cells, cell fusion, and neuroprotection of the dying cells. Here we demonstrate that a restricted number of cells with differentiated astroglial features can be obtained from human adult MSCs (hMSCs) both in vitro using different induction protocols and in vivo after transplantation into the developing mouse brain. We then examined the in vitro differentiation capacity of the hMSCs in coculture with slices of neonatal brain cortex. In this condition the hMSCs did not show any neuronal transdifferentiation but expressed neurotrophin low-affinity (NGFR(p75)) and high-affinity (trkC) receptors and released nerve growth factor (NGF) and neurotrophin-3 (NT-3). The same neurotrophin's expression was demonstrated 45 days after the intracerebral transplantation of hMSCs into nude mice with surviving astroglial cells. These data further confirm the limited capability of adult hMSC to differentiate into neurons whereas they differentiated in astroglial cells. Moreover, the secretion of neurotrophic factors combined with activation of the specific receptors of transplanted hMSCs demonstrated an alternative mechanism for neuroprotection of degenerating neurons. hMSCs are further defined in their transplantation potential for treating neurological disorders.
在脑缺血、帕金森病和脊髓损伤等神经疾病的动物模型中，据报道间充质干细胞（MSCs）移植可改善功能结局。关于MSCs的作用，已提出三种机制：移植细胞转分化以替代退化的神经细胞、细胞融合以及对濒死细胞的神经保护。在此我们证明，使用不同诱导方案在体外以及将其移植到发育中的小鼠脑内后，均可从成人MSCs（hMSCs）中获得数量有限的具有分化星形胶质细胞特征的细胞。然后我们检测了hMSCs与新生脑皮质切片共培养时的体外分化能力。在此条件下，hMSCs未显示任何神经元转分化，但表达神经营养因子低亲和力（NGFR(p75)）和高亲和力（trkC）受体，并释放神经生长因子（NGF）和神经营养因子-3（NT-3）。将hMSCs脑内移植到裸鼠体内45天后，存活的星形胶质细胞也显示出相同的神经营养因子表达。这些数据进一步证实了成人hMSC分化为神经元的能力有限，而它们可分化为星形胶质细胞。此外，神经营养因子的分泌以及移植hMSCs特异性受体的激活证明了对退化神经元进行神经保护的另一种机制。hMSCs在治疗神经疾病方面的移植潜力得到了进一步明确。
