Effect of systemic transplantation of bone marrow-derived mesenchymal stem cells on neuropathology markers in APP/PS1 Alzheimer mice.

AIMS: Mesenchymal stem cells (MSC) have recently attracted interest as a potential basis for a cell-based therapy of AD. We investigated the putative immune-modulatory effects in neuroinflammation of systemic transplantation of MSC into APP/PS1 transgenic mice. METHODS: 106 MSC were injected into APP/PS1 mice via the tail vein and histological analysis was performed for microglia and amyloid (pE3-Aß) plaque numbers, glial distribution and pE3-Aß plaque size. In addition, a biochemical analysis by qPCR for pro-inflammatory, chemoattractant and neurotrophic factors was performed. RESULTS: MSC are associated with pE3-Aß plaques. The effects of transplantation on microglia-associated pathology could be observed after 28 days. Animals showed a reduction in microglial numbers in the cortex and in microglia size. Gene expression was reduced for TNF-α, IL-6, MCP-1, and for NGF, in MSC recipients. Also, we investigated for the first time and found no changes in expression of IL-10, CCR5, BDNF, VEGF and IFNγ. PTGER2 expression levels were increased in the hippocampus but were reduced in the cortex of MSC recipients. While there were no transplant-related changes in pE3-Aß plaque numbers, a reduction in the size of pE3-Aß plaques was observed in the hippocampus of transplant recipients. CONCLUSION: This is the first study to show reduction in pE3-Aß plaque size. pE3-Aß plaques have gained attention as potential key participants in AD due to their increased aggregation propensity, the possibility for the initial seeding event, resistance against degradation and neurotoxicity. These findings support the hypothesis that MSC-transplants may affect AD pathology via an immune-modulatory function that includes an effect on microglial cells.

In Vitro Expression of the Extracellular Matrix Components Aggrecan, Collagen Types I and II by Articular Cartilage-Derived Chondrocytes.

The extracellular matrix (ECM) of hyaline cartilage is perfectly suited to transmit articular pressure load to the subchondral bone. Pressure is transferred by a high amount of aggrecan-based proteoglycans and collagen type II fibres in particular. After any injury, the hyaline cartilage is replaced by fibrocartilage, which is low in proteoglycans and contains collagen type I predominantly. Until now, long-term results of therapeutic procedures including cell-based therapies like autologous chondrocyte transplantation (ACT) lead to a replacement tissue meeting the composition of fibrocartilage. Therefore, it is of particular interest to discover how and to what extent isolation and in vitro cultivation of chondrocytes affect the cells and their expression of ECM components. Hyaline cartilage-derived chondrocytes were cultivated in vitro and observed microscopically over a time period of 35 days. The expression of collagen type I, collagen type II and aggrecan was analysed using RT-qPCR and Western blot at several days of cultivation. Chondrocytes presented a longitudinal shape for the entire cultivation period. While expression of collagen type I prevailed within the first days, only prolonged cultivation led to an increase in collagen type II and aggrecan expression. The results indicate that chondrocyte isolation and in vitro cultivation lead to a dedifferentiation at least to the stage of chondroprogenitor cells.