Iberl, Sabine and Meyer, Anne-Louise and Mueller, Gunnar and Peters, Sebastian and Johannesen, Siw and Kobor, Ines and Beier, Fabian and Bruemmendorf, Tim H. and Hart, Christina and Schelker, Roland and Herr, Wolfgang and Bogdahn, Ulrich and Grassinger, Jochen (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. pp. 192-201. ISSN 1043-4666, 1096-0023
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | COLONY-STIMULATING FACTOR; ENDOTHELIAL GROWTH-FACTOR; BONE-MARROW; T-LYMPHOCYTES; EXPRESSION; SAFETY; BLOOD; TRANSPLANTATION; LEUKEMIA; KINETICS; Amyotrophic lateral sclerosis, ALS; Granulocyte-colony stimulating factor, G-CSF; Hematopoietic stem and progenitor cells, HSPC; Telomere length; Cytokines |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Lehrstuhl für Neurologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 01 Apr 2020 09:41 |
| Last Modified: | 01 Apr 2020 09:41 |
| URI: | https://pred.uni-regensburg.de/id/eprint/26580 |
Actions (login required)
 |
View Item |
