Effects of continuous high-dose G-CSF administration on hematopoietic stem cell mobilization and telomere length in patients with amyotrophic lateral sclerosis – a pilot study
Iberl S, Meyer AL, Mueller G, Peters S, Johannesen S, Kobor I, Beier F, Bruemmendorf TH, Hart C, Schelker R, Herr W, Bogdahn U, Grassinger J (2019)
Publication Type: Journal article
Publication year: 2019
Journal
Book Volume: 120
Pages Range: 192-201
DOI: 10.1016/j.cyto.2019.05.003
Abstract
Amyotrophic lateral sclerosis (ALS)is a neurodegenerative disease of complex and still poorly understood etiology. Loss of upper and lower motoneurons results in death within few years after diagnosis. Recent studies have proposed neuroprotective and disease-slowing effects of granulocyte-colony stimulating factor (G-CSF)treatment in ALS mouse models as well as humans. In this study, six ALS patients were monitored up to 3.5 years during continuous high-dose G-CSF administration. Repetitive analyses were performed including blood count parameters, CD34+ hematopoietic stem and progenitor cell (HSPC)and colony forming cell (CFC)counts, serum cytokine levels and leukocyte telomere length. We demonstrate that continuous G-CSF therapy was well tolerated and safe resulting in only mild adverse events during the observation period. However, no mobilization of CD34+ HSPC was detected as compared to baseline values. CFC mobilization was equally low and even a decrease of myeloid precursors was observed in some patients. Assessment of telomere length within ALS patients’ leukocytes revealed that G-CSF did not significantly shorten telomeres, while those of ALS patients were shorter compared to age-matched healthy controls, irrespective of G-CSF treatment. During G-CSF stimulation, TNF-alpha, CRP, IL-16, sVCAM-1, sICAM-1, Tie-2 and VEGF were significantly increased in serum whereas MCP-1 levels decreased. In conclusion, our data show that continuous G-CSF treatment fails to increase circulating CD34+ HSPC in ALS patients. Cytokine profiles revealed G-CSF-mediated immunomodulatory and proteolytic effects. Interestingly, despite intense G-CSF stimulation, telomere length was not significantly shortened.
Involved external institutions
Universitätsklinikum Regensburg
Germany (DE)
Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen
Germany (DE)
Germany (DE)
Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen
Germany (DE)
How to cite
APA:
Iberl, S., Meyer, A.-L., Mueller, G., Peters, S., Johannesen, S., Kobor, I.,... Grassinger, J. (2019). Effects of continuous high-dose G-CSF administration on hematopoietic stem cell mobilization and telomere length in patients with amyotrophic lateral sclerosis – a pilot study. Cytokine, 120, 192-201. https://doi.org/10.1016/j.cyto.2019.05.003
MLA:
Iberl, Sabine, et al. "Effects of continuous high-dose G-CSF administration on hematopoietic stem cell mobilization and telomere length in patients with amyotrophic lateral sclerosis – a pilot study." Cytokine 120 (2019): 192-201.
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