The protective effects of mesenchymal stromal cells

15 April 2014

The ALS research group at Hannover Medical School has analysed the protective effects of mesenchymal stromal cells on motor neurons. Their study was recently published in PLoS One.

The study performed by members of the ALS research group led by Professor Susanne Petri analysed the protective effects of mesenchymal stromal cells (MSC)on motor neurons (derived from both non-transgenic and mutant SOD1G93A transgenic mice), NSC-34 motor neuron-like cells and astrocytes (derived again from both non-transgenic and mutant SOD1G93A transgenic mice) in vitro, as published recently in PLOS ONE. Sun H et al., Therapeutic potential of mesenchymal stromal cells and MSC conditioned medium in Amyotrophic Lateral Sclerosis (ALS)-in vitro evidence from primary motor neuron cultures, NSC-34 cells, astrocytes and microglia. PLoS One. 2013 Sep 12;8(9):e72926.

MSC conditioned medium (MSC CM) had significant effects against staurosporine-induced apoptosis in non-transgenic and SOD1G93A motor neurons and astrocytes and also in NSC-34 cells (a hybrid cell line produced by the fusion of motor neuron-enriched embryonic mouse spinal cord cells with mouse neuroblastoma). Use of specific inhibitors revealed evidence for involvement of the PI3-K/Akt and MAPK/Erk 1/2-pathways into this protective effect. Expression of the neurotrophic factors GDNF and CNTF in both non-transgenic and SOD1G93A transgenic astrocytes was significantly increased by the presence of MSC conditioned medium. It remains noteworthy that non-transgenic and SOD1G93A astrocytes showed differences in their response to MSC CM: MSC CM induced GDNF expression was significantly higher in SOD1G93A transgenic astrocytes, CNTF mRNA expression was significantly increased upon MSC CM incubation only in non-transgenic astrocytes. These possibly disease-/ genotype-specific differences certainly will require further elucidation.

In addition to induction of growth factor expression, modulation of astrocytic cytokines/ enzymes by MSC CM was observed. Gene expression of the neuroprotective chemokine Fractalkine (CX3CL1) was upregulated in mutant SOD1G93A transgenic astrocytes by MSC CM treatment and the respective receptor, CX3CR1, was upregulated in mutant SOD1G93A transgenic microglia. Further in vitro studies and further comparison of the differential responses of non-transgenic versus SOD1G93A transgenic astrocytes and microglial cells will help to more precisely delineate the potential mechanisms of action of MSC in ALS.

This line of research including development of MSC isolation, quality control and clinical scale-up according to good manufacturing practice (GMP) criteria as well as further in vitro and in vivo studies  is supported by the Integrated Research and Treatment Center Transplantation (IFB-Tx) at Hanover Medical School (funded by the Federal Ministry of Research) which has the overall aim to develop new diagnostic and therapeutic strategies and to integrate and focus transplantation medicine and research.