Lamin A deregulation in human mesenchymal stem cells promotes an impairment in their chondrogenic potential and imbalance in their response to oxidative stress

Abstract

In the present study, we examined the effect of the over-expression of LMNA, or its mutant form progerin (PG), on the mesoderm differentiation potential of mesenchymal stem cells (MSCs) from human umbilical cord (UC) stroma using a recently described differentiation model employing spheroid formation. Accumulation of lamin A (LMNA) was previously associated with the osteoarthritis (OA) chondrocyte phenotype. Mutations of this protein are linked to laminopathies and specifically to Hutchinson-Gilford Progeria Syndrome (HGPS), an accelerated aging disease. Some authors have proposed that a deregulation of LMNA affects the differentiation potential of stem cells. The chondrogenic potential is defective in PG-MSCs, although both PG and LMNA transduced MSCs, have an increase in hypertrophy markers during chondrogenic differentiation. Furthermore, both PG and LMNA-MSCs showed a decrease in manganese superoxide dismutase (MnSODM), an increase of mitochondrial MnSODM-dependent reactive oxygen species (ROS) and alterations in their migration capacity. Finally, defects in chondrogenesis are partially reversed by periodic incubation with ROS-scavenger agent that mimics MnSODM effect. Our results indicate that over-expression of LMNA or PG by lentiviral gene delivery leads to defects in chondrogenic differentiation potential partially due to an imbalance in oxidative stress.

Mesenchymal stem cell aging: Mechanisms and influences on skeletal and non-skeletal tissues

“…72,73 Knockdown of Lamin A/C in human MSCs led to biased differentiation into adipocyte while sacrificing osteoblast and chondrocyte. 74,75 Ablation of ZMPSTE24, an enzyme required for Lamin maturation, causes aging and osteoporosis. ZMPSTE24 deficient osteoblasts showed an increase in PPARg and a decrease in Runx2.…”

The Neuroprotective Effects of Muscle-Derived Stem Cells via Brain-Derived Neurotrophic Factor in Spinal Cord Injury Model

“…Apoptosis is one of the major events in secondary injury, which affects the survivability of neurons and implanted cells [13]. During apoptosis progression, Bax is considered an important proapoptotic protein, and Bcl-2 prevents apoptosis by downregulating Bax [14].…”

Gene therapy of ovarian cancer using IL-21-secreting human umbilical cord mesenchymal stem cells in nude mice

“…Then IL-21 expression was analyzed by western blotting. To identify the bioactivity of UCMSCs-LV-IL-21, the splenocytes from the normal nude mice were incubated with the supernatant from the cultured hUCMSCs-LV-IL-21 for 72 h, then the splenocyte proliferative activity was detected by FCM as described in a previous report [27]. …”