Human adipose-Derived Mesenchymal Stem Cells Improve Motor Functions and are Neuroprotective in the 6-Hydroxydopamine-Rat Model for Parkinson's Disease when Cultured in Monolayer Cultures but Suppress Hippocampal Neurogenesis and Hippocampal Memory Function when Cultured in Spheroids

被引：52

作者：

Berg, Juergen ^{[1
]}

Roch, Manfred ^{[2
]}

Altschueler, Jennifer ^{[1
]}

Winter, Christine ^{[3
]}

Schwerk, Anne ^{[1
]}

Kurtz, Andreas ^{[2
]}

Steiner, Barbara ^{[1
]}

机构：

[1] Charite, Dept Neurol, CCM, D-10117 Berlin, Germany

[2] Charite, Inst Immunol, D-13353 Berlin, Germany

[3] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Psychiat, D-01307 Dresden, Germany

来源：

STEM CELL REVIEWS AND REPORTS | 2015年 / 11卷 / 01期

关键词：

Monolayer and sheproid cultured adipose-derived stem cells; Parkinson's disease; Regeneration; Plasticity; STROMAL CELLS; SUBSTANTIA-NIGRA; BONE-MARROW; RAT MODEL; DOPAMINERGIC-NEURONS; IN-VITRO; NEURAL DIFFERENTIATION; NEUROTROPHIC FACTOR; BASAL GANGLIA; ADULT;

D O I：

10.1007/s12015-014-9551-y

中图分类号：

Q813 [细胞工程];

学科分类号：

100113 [医学细胞生物学];

摘要：

Adult human adipose-derived mesenchymal stem cells (MSC) have been reported to induce neuroprotective effects in models for ParkinsonA ' s disease (PD). However, these effects strongly depend on the most optimal application of the transplant. In the present study we compared monolayer-cultured (aMSC) and spheroid (sMSC) MSC following transplantation into the substantia nigra (SN) of 6-OHDA lesioned rats regarding effects on the local microenvironment, degeneration of dopaminergic neurons, neurogenesis in the hippocampal DG as well as motor and memory function in the 6-OHDA-rat model for PD. aMSC transplantation significantly increased tyrosine hydroxylase (TH) and brain-derived neurotrophic factor (BDNF) levels in the SN, increased the levels of the glial fibrillary acidic protein (GFAP) and improved motor functions compared to untreated and sMSC treated animals. In contrast, sMSC grafting induced an increased local microgliosis, decreased TH levels in the SN and reduced numbers of newly generated cells in the dentate gyrus (DG) without yet affecting hippocampal learning and memory function. We conclude that the neuroprotective potential of adipose-derived MSC in the rat model of PD crucially depends on the applied cellular phenotype.

引用

页码：133 / 149

页数：17

共 87 条

[1]

MICROGLIAL RESPONSE TO 6-HYDROXYDOPAMINE-INDUCED SUBSTANTIA NIGRA LESIONS [J].