Hematopoietic stem and progenitor cells as novel prognostic biomarkers of longevity in a murine model for amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a difficult diagnosis and prognosis. In this regard, new and more reliable biomarkers for the disease are needed. We propose peripheral blood, and, more specifically, the hematopoietic stem and progenitor cells (HSPCs) as potential prognostic biomarkers in the SOD1G93A murine model of ALS. We accurately and serially studied three HSPCs-hematopoietic stem cells (HSCs), common lymphoid progenitors (CLPs), and common myeloid progenitors (CMPs)-in both control and SOD1G93A mice along the disease's progression by RT-PCR and flow cytometry analysis. We found interesting differences for every HSPC type in the transgenic mice compared with the control mice at every time point selected, as well as differences along the disease course. The results showed a maintained compensatory increase of HSCs along disease progression. However, the downregulated levels of CLPs and CMPs suggested an exit of these cell populations to the peripheral tissues, probably due to their supporting role to the damaged tissues. In addition, a positive correlation of the percentage of CLPs and CMPs with the longevity was found, as well as a positive correlation of HSCs and CMPs with motor function and weight, thus reinforcing the idea that HSPCs play a relevant role in the longevity of the SOD1G93A mice. On the basis of these results, both CLPs and CMPs could be considered prognostic biomarkers of longevity in this animal model, opening the door to future studies in human patients for their potential clinical use.
Laboratorio de Genética Bioquímica, Veterinary Faculty of Zaragoza, Instituto Agroalimentario de Aragón, Health Research Institute of Aragon, University of Zaragoza, Zaragoza, Spain; and.
Samanta
S
Gasco
Laboratorio de Genética Bioquímica, Veterinary Faculty of Zaragoza, Instituto Agroalimentario de Aragón, Health Research Institute of Aragon, University of Zaragoza, Zaragoza, Spain; and.
Amaya
A
Rando
Laboratorio de Genética Bioquímica, Veterinary Faculty of Zaragoza, Instituto Agroalimentario de Aragón, Health Research Institute of Aragon, University of Zaragoza, Zaragoza, Spain; and.
Pilar
P
Zaragoza
Biochemistry Department, Centre for Biomedical Network Research on Rare Diseases, Health Research Institute, October 12th Hospital, Madrid, Spain.
Alberto
A
García-Redondo
Laboratorio de Genética Bioquímica, Veterinary Faculty of Zaragoza, Instituto Agroalimentario de Aragón, Health Research Institute of Aragon, University of Zaragoza, Zaragoza, Spain; and.
Ana Cristina
AC
Calvo
Laboratorio de Genética Bioquímica, Veterinary Faculty of Zaragoza, Instituto Agroalimentario de Aragón, Health Research Institute of Aragon, University of Zaragoza, Zaragoza, Spain; and osta@unizar.es.
Rosario
R
Osta
D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D004195:Disease Models, Animal; D006412:Hematopoietic Stem Cells / Q000378:metabolism* / Q000473:pathology; D008136:Longevity / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic / Q000378:metabolism; D011379:Prognosis; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology
D015415:Biomarkers
SOD1G93A murine model; amyotrophic lateral sclerosis; biomarkers; hematopoietic stem and progenitor cells; serial blood monitoring