Human blood and marrow side population stem cell and Stro-1 positive bone marrow stromal cell numbers decline with age, with an increase in quality of surviving stem cells: Correlation with cytokines

S. K. Brusnahan, Timothy R McGuire, J. D. Jackson, J. T. Lane, Kevin Lloyd Garvin, B. J. O'Kane, Ann Malone Berger, S. R. Tuljapurkar, M. A. Kessinger, John G Sharp

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32 Citations (Scopus)

Abstract

Hematological deficiencies increase with aging leading to anemias, reduced hematopoietic stress responses and myelodysplasias. This study tested the hypothesis that side population hematopoietic stem cells (SP-HSC) would decrease with aging, correlating with IGF-1 and IL-6 levels and increases in bone marrow fat. Marrow was obtained from the femoral head and trochanteric region of the femur at surgery for total hip replacement (N= 100). Whole trabecular marrow samples were ground in a sterile mortar and pestle and cellularity and fat content determined. Marrow and blood mononuclear cells were stained with Hoechst dye and the SP-HSC profiles acquired. Marrow stromal cells (MSC) were enumerated flow cytometrically employing the Stro-1 antibody, and clonally in the colony forming unit fibroblast (CFU-F) assay. Plasma levels of IGF-1 (ng/ml) and IL-6 (pg/ml) were measured by ELISA. SP-HSC in blood and bone marrow decreased with age but the quality of the surviving stem cells increased. MSC decreased non-significantly. IGF-1 levels (mean = 30.7, SEM = 2) decreased and IL-6 levels (mean = 4.4, SEM = 1) increased with age as did marrow fat (mean = 1.2. mm. fat/g, SEM = 0.04). There were no significant correlations between cytokine levels or fat and SP-HSC numbers. Stem cells appear to be progressively lost with aging and only the highest quality stem cells survive.

Original languageEnglish (US)
Pages (from-to)718-722
Number of pages5
JournalMechanisms of Ageing and Development
Volume131
Issue number11-12
DOIs
StatePublished - Nov 1 2010

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Side-Population Cells
Mesenchymal Stromal Cells
Stem Cells
Cell Count
Bone Marrow
Cytokines
Hematopoietic Stem Cells
Fats
Insulin-Like Growth Factor I
Interleukin-6
Stromal Cells
Population
Colony-Forming Units Assay
Hip Replacement Arthroplasties
Thigh
Femur
Anemia
Blood Cells
Coloring Agents
Fibroblasts

Keywords

  • Aging
  • IGF-1
  • IL-6
  • Marrow fat
  • Stem cells

ASJC Scopus subject areas

  • Aging
  • Developmental Biology

Cite this

@article{1f919a3d03de46e598c6ee8f6a6d01bb,
title = "Human blood and marrow side population stem cell and Stro-1 positive bone marrow stromal cell numbers decline with age, with an increase in quality of surviving stem cells: Correlation with cytokines",
abstract = "Hematological deficiencies increase with aging leading to anemias, reduced hematopoietic stress responses and myelodysplasias. This study tested the hypothesis that side population hematopoietic stem cells (SP-HSC) would decrease with aging, correlating with IGF-1 and IL-6 levels and increases in bone marrow fat. Marrow was obtained from the femoral head and trochanteric region of the femur at surgery for total hip replacement (N= 100). Whole trabecular marrow samples were ground in a sterile mortar and pestle and cellularity and fat content determined. Marrow and blood mononuclear cells were stained with Hoechst dye and the SP-HSC profiles acquired. Marrow stromal cells (MSC) were enumerated flow cytometrically employing the Stro-1 antibody, and clonally in the colony forming unit fibroblast (CFU-F) assay. Plasma levels of IGF-1 (ng/ml) and IL-6 (pg/ml) were measured by ELISA. SP-HSC in blood and bone marrow decreased with age but the quality of the surviving stem cells increased. MSC decreased non-significantly. IGF-1 levels (mean = 30.7, SEM = 2) decreased and IL-6 levels (mean = 4.4, SEM = 1) increased with age as did marrow fat (mean = 1.2. mm. fat/g, SEM = 0.04). There were no significant correlations between cytokine levels or fat and SP-HSC numbers. Stem cells appear to be progressively lost with aging and only the highest quality stem cells survive.",
keywords = "Aging, IGF-1, IL-6, Marrow fat, Stem cells",
author = "Brusnahan, {S. K.} and McGuire, {Timothy R} and Jackson, {J. D.} and Lane, {J. T.} and Garvin, {Kevin Lloyd} and O'Kane, {B. J.} and Berger, {Ann Malone} and Tuljapurkar, {S. R.} and Kessinger, {M. A.} and Sharp, {John G}",
year = "2010",
month = "11",
day = "1",
doi = "10.1016/j.mad.2010.10.002",
language = "English (US)",
volume = "131",
pages = "718--722",
journal = "Mechanisms of Ageing and Development",
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TY - JOUR

T1 - Human blood and marrow side population stem cell and Stro-1 positive bone marrow stromal cell numbers decline with age, with an increase in quality of surviving stem cells

T2 - Correlation with cytokines

AU - Brusnahan, S. K.

AU - McGuire, Timothy R

AU - Jackson, J. D.

AU - Lane, J. T.

AU - Garvin, Kevin Lloyd

AU - O'Kane, B. J.

AU - Berger, Ann Malone

AU - Tuljapurkar, S. R.

AU - Kessinger, M. A.

AU - Sharp, John G

PY - 2010/11/1

Y1 - 2010/11/1

N2 - Hematological deficiencies increase with aging leading to anemias, reduced hematopoietic stress responses and myelodysplasias. This study tested the hypothesis that side population hematopoietic stem cells (SP-HSC) would decrease with aging, correlating with IGF-1 and IL-6 levels and increases in bone marrow fat. Marrow was obtained from the femoral head and trochanteric region of the femur at surgery for total hip replacement (N= 100). Whole trabecular marrow samples were ground in a sterile mortar and pestle and cellularity and fat content determined. Marrow and blood mononuclear cells were stained with Hoechst dye and the SP-HSC profiles acquired. Marrow stromal cells (MSC) were enumerated flow cytometrically employing the Stro-1 antibody, and clonally in the colony forming unit fibroblast (CFU-F) assay. Plasma levels of IGF-1 (ng/ml) and IL-6 (pg/ml) were measured by ELISA. SP-HSC in blood and bone marrow decreased with age but the quality of the surviving stem cells increased. MSC decreased non-significantly. IGF-1 levels (mean = 30.7, SEM = 2) decreased and IL-6 levels (mean = 4.4, SEM = 1) increased with age as did marrow fat (mean = 1.2. mm. fat/g, SEM = 0.04). There were no significant correlations between cytokine levels or fat and SP-HSC numbers. Stem cells appear to be progressively lost with aging and only the highest quality stem cells survive.

AB - Hematological deficiencies increase with aging leading to anemias, reduced hematopoietic stress responses and myelodysplasias. This study tested the hypothesis that side population hematopoietic stem cells (SP-HSC) would decrease with aging, correlating with IGF-1 and IL-6 levels and increases in bone marrow fat. Marrow was obtained from the femoral head and trochanteric region of the femur at surgery for total hip replacement (N= 100). Whole trabecular marrow samples were ground in a sterile mortar and pestle and cellularity and fat content determined. Marrow and blood mononuclear cells were stained with Hoechst dye and the SP-HSC profiles acquired. Marrow stromal cells (MSC) were enumerated flow cytometrically employing the Stro-1 antibody, and clonally in the colony forming unit fibroblast (CFU-F) assay. Plasma levels of IGF-1 (ng/ml) and IL-6 (pg/ml) were measured by ELISA. SP-HSC in blood and bone marrow decreased with age but the quality of the surviving stem cells increased. MSC decreased non-significantly. IGF-1 levels (mean = 30.7, SEM = 2) decreased and IL-6 levels (mean = 4.4, SEM = 1) increased with age as did marrow fat (mean = 1.2. mm. fat/g, SEM = 0.04). There were no significant correlations between cytokine levels or fat and SP-HSC numbers. Stem cells appear to be progressively lost with aging and only the highest quality stem cells survive.

KW - Aging

KW - IGF-1

KW - IL-6

KW - Marrow fat

KW - Stem cells

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U2 - 10.1016/j.mad.2010.10.002

DO - 10.1016/j.mad.2010.10.002

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JO - Mechanisms of Ageing and Development

JF - Mechanisms of Ageing and Development

SN - 0047-6374

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