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

Abstract

Adult human adipose-derived mesenchymal stem cells (MSC) have been reported to induce neuroprotective effects in models for Parkinson'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.

Adipose-Derived Human Mesenchymal Stem Cells Induce Long-Term Neurogenic and Anti-Inflammatory Effects and Improve Cognitive but not Motor Performance in a Rat Model of Parkinson's Disease

“…Furthermore, neuronal loss in the OB showed a strong correlation with disease duration in PD [5], implicating a progressive degeneration of OB neurons. Furthermore, our colleagues showed a profound effect of AD-MSC on TH and BDNF levels and on motor behavior in Parkinsonian rats [27]. In line with previous studies [4], we found a positive correlation between the amount of subventricular BrdU+/ HuD+ neurons and the amount of dopaminergic neurons in all groups, indicating a relationship of increased neurogenesis with increased dopaminergic tone.…”

Intracarotid Infusion of Mesenchymal Stem Cells in an Animal Model of Parkinson's Disease, Focusing on Cell Distribution and Neuroprotective and Behavioral Effects

“…More recently, stem cells have been proposed as a promising tool to achieve neurorestoration in the PD brain. Numerous studies have been conducted in PD animal models, with different stem cell types, including embryonic [5][6][7] or adult neural stem cells [8], dopaminergic cells differentiated from fibroblast-derived inducible pluripotent stem (iPS) cells [9][10][11] and bone marrow-and adiposederived mesenchymal stem cells (MSCs) [12][13][14][15][16][17][18][19][20][21][22].…”

Adipose‐derived stem cells decreased microglia activation and protected dopaminergic loss in rat lipopolysaccharide model

“…However, the use of MSCs as an effective PD treatment is still controversial because MSCs can both stimulate and inhibit the immune system (Dazzi et al, 2012;English & Mahon, 2011;Yagi et al, 2010). In fact, some authors have demonstrated a neuroprotective effect of these cells in vitro and in vivo (Ooi, Dheen, & Tay, 2015;Schwerk et al, 2015;Stemberger et al, 2011;F. Wang et al, 2010), but other authors could not demonstrate it (Camp, Loeffler, Farrah, Borneman, & LeWitt, 2009;Eliopoulos et al, 2005).…”