title: Aging impairs long-term hematopoietic regeneration after autologous stem cell transplantation.
abstract: Most of our knowledge of the effects of aging on the hematopoietic system comes from studies in animal models. In this study, to explore potential effects of aging on human hematopoietic stem and progenitor cells (HSPCs), we evaluated CD34(+) cells derived from young (<35 years) and old (>60 years) adult bone marrow with respect to phenotype and in vitro function. We observed an increased frequency of phenotypically defined stem and progenitor cells with age, but no distinct differences with respect to in vitro functional capacity. Given that regeneration of peripheral blood counts can serve as a functional readout of HSPCs, we compared various peripheral blood parameters between younger patients (≤50 years; n = 64) and older patients (≥60 years; n = 55) after autologous stem cell transplantation. Patient age did not affect the number of apheresis cycles or the amount of CD34(+) cells harvested. Parameters for short-term regeneration did not differ significantly between the younger and older patients; however, complete recovery of all 3 blood lineages at 1 year after transplantation was strongly affected by advanced age, occurring in only 29% of the older patients, compared with 56% of the younger patients (P = .009). Collectively, these data suggest that aging has only limited effects on CD34(+) HSPCs under steady-state conditions, but can be important under consitions of chemotoxic and replicative stress.
authors.affiliation: Department of Experimental Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. Electronic address: c.m.woolthuis@umcg.nl.
authors.forename: Carolien M
authors.initials: CM
authors.lastname: Woolthuis
authors.affiliation: Department of Experimental Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Niccoló
authors.initials: N
authors.lastname: Mariani
authors.affiliation: Department of Experimental Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Rikst Nynke
authors.initials: RN
authors.lastname: Verkaik-Schakel
authors.affiliation: Department of Experimental Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Annet Z
authors.initials: AZ
authors.lastname: Brouwers-Vos
authors.affiliation: Department of Experimental Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Jan Jacob
authors.initials: JJ
authors.lastname: Schuringa
authors.affiliation: Department of Experimental Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Edo
authors.initials: E
authors.lastname: Vellenga
authors.affiliation: Department of Experimental Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Joost T M
authors.initials: JT
authors.lastname: de Wolf
authors.affiliation: Department of Experimental Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. Electronic address: gerwin.huls@radboudumc.nl.
authors.forename: Gerwin
authors.initials: G
authors.lastname: Huls
mesh_terms: D000328:Adult; D000367:Age Factors; D018952:Antigens, CD34 / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D006410:Hematopoiesis / Q000502:physiology; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000628:therapy; D014182:Transplantation, Autologous; D055815:Young Adult
chemical_list: D018952:Antigens, CD34
keywords: Aging; Autologous stem cell transplantation; Hematopoietic progenitor cell; Hematopoietic stem cell