TY - JOUR
T1 - Mesenchymal stromal cells from donors varying widely in age are of equal cellular fitness after in vitro expansion under hypoxic conditions
AU - Lund, Troy C.
AU - Kobs, Amanda
AU - Blazar, Bruce R.
AU - Tolar, Jakub
N1 - Funding Information:
Supported by the Children's Cancer Research Fund , Minneapolis, MN.
PY - 2010/12
Y1 - 2010/12
N2 - Background aims. Mesenchymal stromal cells (MSC) are gaining in popularity as an experimental therapy for a number of conditions that often require expansion ex vivo prior to use. Data comparing clinical-grade MSC from various ages of donors are scant. We hypothesized that MSC from older donors may display differences in cellular fitness when expanded for clinical use. Methods. We evaluated the expression of several markers of aging, oxidative stress and growth kinetics, and telomere length, in MSC obtained from a wide age range (8 months to 58 years). Results. To evaluate cellular fitness we compared MSC expanded from younger (8 months6 years) versus older (3858 years) donors in terms of selected cell-surface markers, lipofuscin, migration ability, telomere length and expression of iNOS, PGE2, p16INK and SOD. Results did not differ between these groups. Neither SOD activity (0.025 versus 0.028 U/mL) nor death after oxidative challenge was significantly different (1% versus 1.5%, P 0.14). We did find that, although MSC from older individuals produced slightly fewer cells over a 28-day culture period and had a slightly longer doubling time (54 h versus 42 hr, a satisfactory clinical product could still be obtained regardless of age cohort. Conclusions. Collectively, these data show that MSC can be expanded without significant alterations in expansile properties or obvious changes in parameters associated with senescence. Because cellular fitness was equivalent in these cohorts, MSC from donors up to age 58 years can be used as a source of cells for cellular therapy.
AB - Background aims. Mesenchymal stromal cells (MSC) are gaining in popularity as an experimental therapy for a number of conditions that often require expansion ex vivo prior to use. Data comparing clinical-grade MSC from various ages of donors are scant. We hypothesized that MSC from older donors may display differences in cellular fitness when expanded for clinical use. Methods. We evaluated the expression of several markers of aging, oxidative stress and growth kinetics, and telomere length, in MSC obtained from a wide age range (8 months to 58 years). Results. To evaluate cellular fitness we compared MSC expanded from younger (8 months6 years) versus older (3858 years) donors in terms of selected cell-surface markers, lipofuscin, migration ability, telomere length and expression of iNOS, PGE2, p16INK and SOD. Results did not differ between these groups. Neither SOD activity (0.025 versus 0.028 U/mL) nor death after oxidative challenge was significantly different (1% versus 1.5%, P 0.14). We did find that, although MSC from older individuals produced slightly fewer cells over a 28-day culture period and had a slightly longer doubling time (54 h versus 42 hr, a satisfactory clinical product could still be obtained regardless of age cohort. Conclusions. Collectively, these data show that MSC can be expanded without significant alterations in expansile properties or obvious changes in parameters associated with senescence. Because cellular fitness was equivalent in these cohorts, MSC from donors up to age 58 years can be used as a source of cells for cellular therapy.
KW - aging
KW - bone marrow stroma
KW - mesenchymal stromal cell
KW - oxidative stress
KW - telomere
UR - http://www.scopus.com/inward/record.url?scp=78649271748&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78649271748&partnerID=8YFLogxK
U2 - 10.3109/14653249.2010.509394
DO - 10.3109/14653249.2010.509394
M3 - Article
C2 - 20807020
AN - SCOPUS:78649271748
SN - 1465-3249
VL - 12
SP - 971
EP - 981
JO - Cytotherapy
JF - Cytotherapy
IS - 8
ER -